PTSD

Young Black adults who witness or experience police violence have significantly elevated levels of anxiety, new research shows.

In the first study to quantify the impact of police contact anxiety, investigators found it was associated with moderately severe anxiety levels in this group of individuals, highlighting the need to screen for exposure to police violence in this patient population, study investigator Robert O. Motley Jr, PhD, manager of the Race & Opportunity Lab at Washington University in St. Louis, said in an interview.

“If you’re working in an institution and providing clinical care, mental health care, or behavior health care, these additional measures should be included to get a much more holistic view of the exposure of these individuals in terms of traumatic events. These assessments can inform your decisions around care,” Dr. Motley added.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

‘Alarming’ rates of exposure

Evidence shows anxiety disorders are among the most prevalent conditions for Black people aged 18-29 years – an age group described as “emergent adulthood” because these individuals haven’t yet taken on full responsibilities of adulthood.

Research shows Black emergent adults are three to four times more likely than other ethnic groups to be exposed to actual or threatened nonfatal police violence, said Dr. Motley. “So they didn’t die, but were exposed to force, which could be things like police yelling at them, hitting or kicking them, pointing a gun at them, or tasing them.”

These individuals are also two to three times more likely to experience exposure to fatal police violence, and to be unarmed and killed, said Dr. Motley.

Evidence shows a clear link between exposure to stressful or traumatic events and anxiety disorders, but there has been little research examining the relationship between exposure to police violence and anxiety disorders among Black emergent adults, he said.

To assess the prevalence and correlates of “police contact anxiety” the investigators used computer-assisted surveys to collect data from 300 young Black college students in St. Louis who had been exposed to police violence at some point in their lives. The mean age of the sample was 20.4 years and included an equal number of men and women.

Work status for the previous year showed almost one-quarter (23.6%) were unemployed and about half worked part time. Almost two-thirds (62.6%) had an annual income of less than $10,000.

Respondents reported they had personally experienced police violence almost twice (a mean of 1.89) during their lifetime. The mean number of times they witnessed police using force against someone else was 7.82. Respondents also reported they had watched videos showing police use of force on the internet or television an average of 34.5 times.

This, said Dr. Motley, isn’t surprising given the growing number of young adults – of all races – who are using social media platforms to upload and share videos.

The researchers also looked at witnessing community violence, unrelated to police violence. Here, respondents had an average of 10.9 exposures.

“These results tell me these individuals are exposed to high levels of violence in their lifetime, which should be alarming,” said Dr. Motley.
 

Protectors or predators?

To examine the impact of police contact anxiety caused either by direct experience, or as a result of witnessing, or seeing a video of police use of violence in the past 30 days, the researchers created a “police contact anxiety” scale.

Respondents were asked six questions pertaining specifically to experiences during, or in anticipation of, police contact and its effects on anxiety levels.

For each of the six questions, participants rated the severity of anxiety on a scale of 0 (least severe) to 3 (most severe) for each exposure type. The final score had a potential range of 0-24.

Results showed police contact anxiety was moderately severe for all three exposure types with scores ranging from 13 to 14.

Ordinary least square regression analyses showed that, compared with unemployed participants, those who worked full time were less likely to have higher police contact anxiety as a result of seeing a video of police use of force (P < .05) – a finding Dr. Motley said was not surprising.

Employment, he noted, promotes individual self-efficacy, social participation, and mental health, which may provide a “buffer” to the effects of watching videos of police violence.

Dr. Motley noted that police officers “have been entrusted to serve and protect” the community, but “rarely face consequences when they use force against Black emergent adults; they’re rarely held accountable.”

These young Black adults “may perceive police officers as more of a threat to personal safety instead of a protector of it.”

Additional bivariate analyses showed that males had significantly higher scores than females for police contact anxiety because of witnessing police use of force.

This, too, was not surprising since males are exposed to more violence in general, said Dr. Motley.

It’s important to replicate the findings using a much larger and more diverse sample, he said. His next research project will be to collect data from a nationally representative sample of emerging adults across different ethnic groups and examining a range of different variables.

Commenting on the findings, Jeffrey Borenstein, MD, president and CEO of the Brain & Behavior Research Foundation and editor in chief of Psychiatric News, called it “outstanding.”

“This is a very important issue,” said Dr. Borenstein, who moderated a press briefing that featured the study.

“We know anxiety is an extremely important condition and symptom, across the board for all groups, and often anxiety isn’t evaluated in the way that it needs to be. This is a great study that will lead to further research in this important area,” he added.

The study was funded by the National Institute on Minority Health and Health Disparities. Dr. Motley and Dr. Borenstein have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Young Black adults who witness or experience police violence have significantly elevated levels of anxiety, new research shows.

In the first study to quantify the impact of police contact anxiety, investigators found it was associated with moderately severe anxiety levels in this group of individuals, highlighting the need to screen for exposure to police violence in this patient population, study investigator Robert O. Motley Jr, PhD, manager of the Race & Opportunity Lab at Washington University in St. Louis, said in an interview.

“If you’re working in an institution and providing clinical care, mental health care, or behavior health care, these additional measures should be included to get a much more holistic view of the exposure of these individuals in terms of traumatic events. These assessments can inform your decisions around care,” Dr. Motley added.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

‘Alarming’ rates of exposure

Evidence shows anxiety disorders are among the most prevalent conditions for Black people aged 18-29 years – an age group described as “emergent adulthood” because these individuals haven’t yet taken on full responsibilities of adulthood.

Research shows Black emergent adults are three to four times more likely than other ethnic groups to be exposed to actual or threatened nonfatal police violence, said Dr. Motley. “So they didn’t die, but were exposed to force, which could be things like police yelling at them, hitting or kicking them, pointing a gun at them, or tasing them.”

These individuals are also two to three times more likely to experience exposure to fatal police violence, and to be unarmed and killed, said Dr. Motley.

Evidence shows a clear link between exposure to stressful or traumatic events and anxiety disorders, but there has been little research examining the relationship between exposure to police violence and anxiety disorders among Black emergent adults, he said.

To assess the prevalence and correlates of “police contact anxiety” the investigators used computer-assisted surveys to collect data from 300 young Black college students in St. Louis who had been exposed to police violence at some point in their lives. The mean age of the sample was 20.4 years and included an equal number of men and women.

Work status for the previous year showed almost one-quarter (23.6%) were unemployed and about half worked part time. Almost two-thirds (62.6%) had an annual income of less than $10,000.

Respondents reported they had personally experienced police violence almost twice (a mean of 1.89) during their lifetime. The mean number of times they witnessed police using force against someone else was 7.82. Respondents also reported they had watched videos showing police use of force on the internet or television an average of 34.5 times.

This, said Dr. Motley, isn’t surprising given the growing number of young adults – of all races – who are using social media platforms to upload and share videos.

The researchers also looked at witnessing community violence, unrelated to police violence. Here, respondents had an average of 10.9 exposures.

“These results tell me these individuals are exposed to high levels of violence in their lifetime, which should be alarming,” said Dr. Motley.
 

Protectors or predators?

To examine the impact of police contact anxiety caused either by direct experience, or as a result of witnessing, or seeing a video of police use of violence in the past 30 days, the researchers created a “police contact anxiety” scale.

Respondents were asked six questions pertaining specifically to experiences during, or in anticipation of, police contact and its effects on anxiety levels.

For each of the six questions, participants rated the severity of anxiety on a scale of 0 (least severe) to 3 (most severe) for each exposure type. The final score had a potential range of 0-24.

Results showed police contact anxiety was moderately severe for all three exposure types with scores ranging from 13 to 14.

Ordinary least square regression analyses showed that, compared with unemployed participants, those who worked full time were less likely to have higher police contact anxiety as a result of seeing a video of police use of force (P < .05) – a finding Dr. Motley said was not surprising.

Employment, he noted, promotes individual self-efficacy, social participation, and mental health, which may provide a “buffer” to the effects of watching videos of police violence.

Dr. Motley noted that police officers “have been entrusted to serve and protect” the community, but “rarely face consequences when they use force against Black emergent adults; they’re rarely held accountable.”

These young Black adults “may perceive police officers as more of a threat to personal safety instead of a protector of it.”

Additional bivariate analyses showed that males had significantly higher scores than females for police contact anxiety because of witnessing police use of force.

This, too, was not surprising since males are exposed to more violence in general, said Dr. Motley.

It’s important to replicate the findings using a much larger and more diverse sample, he said. His next research project will be to collect data from a nationally representative sample of emerging adults across different ethnic groups and examining a range of different variables.

Commenting on the findings, Jeffrey Borenstein, MD, president and CEO of the Brain & Behavior Research Foundation and editor in chief of Psychiatric News, called it “outstanding.”

“This is a very important issue,” said Dr. Borenstein, who moderated a press briefing that featured the study.

“We know anxiety is an extremely important condition and symptom, across the board for all groups, and often anxiety isn’t evaluated in the way that it needs to be. This is a great study that will lead to further research in this important area,” he added.

The study was funded by the National Institute on Minority Health and Health Disparities. Dr. Motley and Dr. Borenstein have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Young Black adults who witness or experience police violence have significantly elevated levels of anxiety, new research shows.

In the first study to quantify the impact of police contact anxiety, investigators found it was associated with moderately severe anxiety levels in this group of individuals, highlighting the need to screen for exposure to police violence in this patient population, study investigator Robert O. Motley Jr, PhD, manager of the Race & Opportunity Lab at Washington University in St. Louis, said in an interview.

“If you’re working in an institution and providing clinical care, mental health care, or behavior health care, these additional measures should be included to get a much more holistic view of the exposure of these individuals in terms of traumatic events. These assessments can inform your decisions around care,” Dr. Motley added.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

‘Alarming’ rates of exposure

Evidence shows anxiety disorders are among the most prevalent conditions for Black people aged 18-29 years – an age group described as “emergent adulthood” because these individuals haven’t yet taken on full responsibilities of adulthood.

Research shows Black emergent adults are three to four times more likely than other ethnic groups to be exposed to actual or threatened nonfatal police violence, said Dr. Motley. “So they didn’t die, but were exposed to force, which could be things like police yelling at them, hitting or kicking them, pointing a gun at them, or tasing them.”

These individuals are also two to three times more likely to experience exposure to fatal police violence, and to be unarmed and killed, said Dr. Motley.

Evidence shows a clear link between exposure to stressful or traumatic events and anxiety disorders, but there has been little research examining the relationship between exposure to police violence and anxiety disorders among Black emergent adults, he said.

To assess the prevalence and correlates of “police contact anxiety” the investigators used computer-assisted surveys to collect data from 300 young Black college students in St. Louis who had been exposed to police violence at some point in their lives. The mean age of the sample was 20.4 years and included an equal number of men and women.

Work status for the previous year showed almost one-quarter (23.6%) were unemployed and about half worked part time. Almost two-thirds (62.6%) had an annual income of less than $10,000.

Respondents reported they had personally experienced police violence almost twice (a mean of 1.89) during their lifetime. The mean number of times they witnessed police using force against someone else was 7.82. Respondents also reported they had watched videos showing police use of force on the internet or television an average of 34.5 times.

This, said Dr. Motley, isn’t surprising given the growing number of young adults – of all races – who are using social media platforms to upload and share videos.

The researchers also looked at witnessing community violence, unrelated to police violence. Here, respondents had an average of 10.9 exposures.

“These results tell me these individuals are exposed to high levels of violence in their lifetime, which should be alarming,” said Dr. Motley.
 

Protectors or predators?

To examine the impact of police contact anxiety caused either by direct experience, or as a result of witnessing, or seeing a video of police use of violence in the past 30 days, the researchers created a “police contact anxiety” scale.

Respondents were asked six questions pertaining specifically to experiences during, or in anticipation of, police contact and its effects on anxiety levels.

For each of the six questions, participants rated the severity of anxiety on a scale of 0 (least severe) to 3 (most severe) for each exposure type. The final score had a potential range of 0-24.

Results showed police contact anxiety was moderately severe for all three exposure types with scores ranging from 13 to 14.

Ordinary least square regression analyses showed that, compared with unemployed participants, those who worked full time were less likely to have higher police contact anxiety as a result of seeing a video of police use of force (P < .05) – a finding Dr. Motley said was not surprising.

Employment, he noted, promotes individual self-efficacy, social participation, and mental health, which may provide a “buffer” to the effects of watching videos of police violence.

Dr. Motley noted that police officers “have been entrusted to serve and protect” the community, but “rarely face consequences when they use force against Black emergent adults; they’re rarely held accountable.”

These young Black adults “may perceive police officers as more of a threat to personal safety instead of a protector of it.”

Additional bivariate analyses showed that males had significantly higher scores than females for police contact anxiety because of witnessing police use of force.

This, too, was not surprising since males are exposed to more violence in general, said Dr. Motley.

It’s important to replicate the findings using a much larger and more diverse sample, he said. His next research project will be to collect data from a nationally representative sample of emerging adults across different ethnic groups and examining a range of different variables.

Commenting on the findings, Jeffrey Borenstein, MD, president and CEO of the Brain & Behavior Research Foundation and editor in chief of Psychiatric News, called it “outstanding.”

“This is a very important issue,” said Dr. Borenstein, who moderated a press briefing that featured the study.

“We know anxiety is an extremely important condition and symptom, across the board for all groups, and often anxiety isn’t evaluated in the way that it needs to be. This is a great study that will lead to further research in this important area,” he added.

The study was funded by the National Institute on Minority Health and Health Disparities. Dr. Motley and Dr. Borenstein have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although the healing properties of cannabis have been touted for millennia, research into its potential neuropsychiatric applications truly began to take off in the 1990s following the discovery of the cannabinoid system in the brain. This led to speculation that cannabis could play a therapeutic role in regulating dopamine, serotonin, and other neurotransmitters and offer a new means of treating various ailments.

LPETTET/Getty Images

At the same time, efforts to liberalize marijuana laws have successfully played out in several nations, including the United States, where, as of April 29, 36 states provide some access to cannabis. These dual tracks – medical and political – have made cannabis an increasingly accepted part of the cultural fabric.

Yet with this development has come a new quandary for clinicians. Medical cannabis has been made widely available to patients and has largely outpaced the clinical evidence, leaving it unclear how and for which indications it should be used.
 

The many forms of medical cannabis

Cannabis is a genus of plants that includes marijuana (Cannabis sativa) and hemp. These plants contain over 100 compounds, including terpenes, flavonoids, and – most importantly for medicinal applications – cannabinoids.

The most abundant cannabinoid in marijuana is the psychotropic delta-9-tetrahydrocannabinol (THC), which imparts the “high” sensation. The next most abundant cannabinoid is cannabidiol (CBD), which is the nonpsychotropic. THC and CBD are the most extensively studied cannabinoids, together and in isolation. Evidence suggests that other cannabinoids and terpenoids may also hold medical promise and that cannabis’ various compounds can work synergistically to produce a so-called entourage effect.

Patients walking into a typical medical cannabis dispensary will be faced with several plant-derived and synthetic options, which can differ considerably in terms of the ratios and amounts of THC and CBD they contain, as well in how they are consumed (i.e., via smoke, vapor, ingestion, topical administration, or oromucosal spray), all of which can alter their effects. Further complicating matters is the varying level of oversight each state and country has in how and whether they test for and accurately label products’ potency, cannabinoid content, and possible impurities.

Medically authorized, prescription cannabis products go through an official regulatory review process, and indications/contraindications have been established for them. To date, the Food and Drug Administration has approved one cannabis-derived drug product – Epidiolex (purified CBD) – for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients aged 2 years and older. The FDA has also approved three synthetic cannabis-related drug products – Marinol, Syndros (or dronabinol, created from synthetic THC), and Cesamet (or nabilone, a synthetic cannabinoid similar to THC) – all of which are indicated for treatment-related nausea and anorexia associated with weight loss in AIDS patients.

Surveys of medical cannabis consumers indicate that most people cannot distinguish between THC and CBD, so the first role that physicians find themselves in when recommending this treatment may be in helping patients navigate the volume of options.
 

Promising treatment for pain

Chronic pain is the leading reason patients seek out medical cannabis. It is also the indication that most researchers agree has the strongest evidence to support its use.

“In my mind, the most promising immediate use for medical cannabis is with THC for pain,” Diana M. Martinez, MD, a professor of psychiatry at Columbia University, New York, who specializes in addiction research, said in a recent MDedge podcast. “THC could be added to the armamentarium of pain medications that we use today.”

In a 2015 systematic literature review, researchers assessed 28 randomized, controlled trials (RCTs) of the use of cannabinoids for chronic pain. They reported that a variety of formulations resulted in at least a 30% reduction in the odds of pain, compared with placebo. A meta-analysis of five RCTs involving patients with neuropathic pain found a 30% reduction in pain over placebo with inhaled, vaporized cannabis. Varying results have been reported in additional studies for this indication. The National Academies of Sciences, Engineering, and Medicine concluded that there was a substantial body of evidence that cannabis is an effective treatment for chronic pain in adults.

The ongoing opioid epidemic has lent these results additional relevance. Data indicate that patients with chronic pain who undergo treatment with medical cannabis can reduce their intake of opioids by more than 60%.

Seeing this firsthand has caused Mark Steven Wallace, MD, a pain management specialist and chair of the division of pain medicine at the University of California San Diego Health, to reconsider offering cannabis to his patients.

“I think it’s probably more efficacious, just from my personal experience, and it’s a much lower risk of abuse and dependence than the opioids,” he said.

Dr. Wallace advised that clinicians who treat pain consider the ratios of cannabinoids.

“This is anecdotal, but we do find that with the combination of the two, CBD reduces the psychoactive effects of the THC. The ratios we use during the daytime range around 20 mg of CBD to 1 mg of THC,” he said.

In a recent secondary analysis of an RCT involving patients with painful diabetic peripheral neuropathy, Dr. Wallace and colleagues showed that THC’s effects appear to reverse themselves at a certain level.

“As the THC level goes up, the pain reduces until you reach about 16 ng/mL; then it starts going in the opposite direction, and pain will start to increase,” he said. “Even recreational cannabis users have reported that they avoid high doses because it’s very aversive. Using cannabis is all about, start low and go slow.”
 

A mixed bag for neurologic indications

There are relatively limited data on the use of medical cannabis for other neurologic conditions, and results have varied. For uses other than pain management, the evidence that does exist is strongest regarding epilepsy, said Daniel Freedman, DO, assistant professor of neurology at the University of Texas at Austin. He noted “multiple high-quality RCTs showing that pharmaceutical-grade CBD can reduce seizures associated with two particular epilepsy syndromes: Dravet Syndrome and Lennox Gastaut.”

These findings led to the FDA’s 2018 approval of Epidiolex for these syndromes. In earlier years, interest in CBD for pediatric seizures was largely driven by anecdotal parental reports of its benefits. NASEM’s 2017 overview on medical cannabis found evidence from subsequent RCTs in this indication to be insufficient. Clinicians who prescribe CBD for this indication must be vigilant because it can interact with several commonly used antiepileptic drugs.

Cannabinoid treatments have also shown success in alleviating muscle spasticity resulting from multiple sclerosis, most prominently in the form of nabiximols (Sativex), a standardized oralmucosal spray containing approximately equal quantities of THC and CBD. Nabiximols is approved in Europe but not in the United States. Moderate evidence supports the efficacy of these and other treatments over placebo in reducing muscle spasticity. Patient ratings of its effects tend to be higher than clinician assessment.

Parkinson’s disease has not yet been approved as an indication for treatment with cannabis or cannabinoids, yet a growing body of preclinical data suggests these could influence the dopaminergic system, said Carsten Buhmann, MD, from the department of neurology at the University Medical Center Hamburg-Eppendorf (Germany).

“In general, cannabinoids modulate basal-ganglia function on two levels which are especially relevant in Parkinson’s disease, i.e., the glutamatergic/dopaminergic synaptic neurotransmission and the corticostriatal plasticity,” he said. “Furthermore, activation of the endocannabinoid system might induce neuroprotective effects related to direct receptor-independent mechanisms, activation of anti-inflammatory cascades in glial cells via the cannabinoid receptor type 2, and antiglutamatergic antiexcitotoxic properties.”

Dr. Buhmann said that currently, clinical evidence is scarce, consisting of only four double-blind, placebo-controlled RCTs involving 49 patients. Various cannabinoids and methods of administering treatment were employed. Improvement was only observed in one of these RCTs, which found that the cannabinoid receptor agonist nabilone significantly reduced levodopa-induced dyskinesia for patients with Parkinson’s disease. Subjective data support a beneficial effect. In a nationwide survey of 1,348 respondents conducted by Dr. Buhmann and colleagues, the majority of medical cannabis users reported that it improved their symptoms (54% with oral CBD and 68% with inhaled THC-containing cannabis).

NASEM concluded that there was insufficient evidence to support the efficacy of medical cannabis for other neurologic conditions, including Tourette syndrome, amyotrophic lateral sclerosis, Huntington disease, dystonia, or dementia. A 2020 position statement from the American Academy of Neurology cited the lack of sufficient peer-reviewed research as the reason it could not currently support the use of cannabis for neurologic disorders.

Yet, according to Dr. Freedman, who served as a coauthor of the AAN position statement, this hasn’t stymied research interest in the topic. He’s seen a substantial uptick in studies of CBD over the past 2 years. “The body of evidence grows, but I still see many claims being made without evidence. And no one seems to care about all the negative trials.”
 

Cannabis as a treatment for, and cause of, psychiatric disorders

Mental health problems – such as anxiety, depression, and PTSD – are among the most common reasons patients seek out medical cannabis. There is an understandable interest in using cannabis and cannabinoids to treat psychiatric disorders. Preclinical studies suggest that the endocannabinoid system plays a prominent role in modulating feelings of anxiety, mood, and fear. As with opioids and chronic pain management, there is hope that medical cannabis may provide a means of reducing prescription anxiolytics and their associated risks.

The authors of the first systematic review (BMC Psychiatry. 2020 Jan 16;20[1]:24) of the use of medical cannabis for major psychiatric disorders noted that the current evidence was “encouraging, albeit embryonic.”

Meta-analyses have indicated a small but positive association between cannabis use and anxiety, although this may reflect the fact that patients with anxiety sought out this treatment. Given the risks for substance use disorders among patients with anxiety, CBD may present a more viable option. Positive results have been shown as treatment for generalized social anxiety disorder.

Limited but encouraging results have also been reported regarding the alleviation of PTSD symptoms with both cannabis and CBD, although the body of high-quality evidence hasn’t notably progressed since 2017, when NASEM declared that the evidence was insufficient. Supportive evidence is similarly lacking regarding the treatment of depression. Longitudinal studies suggest that cannabis use, particularly heavy use, may increase the risk of developing this disorder. Because THC is psychoactive, it is advised that it be avoided by patients at risk for psychotic disorders. However, CBD has yielded limited benefits for patients with treatment-resistant schizophrenia and for young people at risk for psychosis.

The use of medical cannabis for psychiatric conditions requires a complex balancing act, inasmuch as these treatments may exacerbate the very problems they are intended to alleviate.

Marta Di Forti, MD, PhD, professor of psychiatric research at Kings College London, has been at the forefront of determining the mental health risks of continued cannabis use. In 2019, Dr. Di Forti developed the first and only Cannabis Clinic for Patients With Psychosis in London where she and her colleagues have continued to elucidate this connection.

Dr. Di Forti and colleagues have linked daily cannabis use to an increase in the risk of experiencing psychotic disorder, compared with never using it. That risk was further increased among users of high-potency cannabis (≥10% THC). The latter finding has troubling implications, because concentrations of THC have steadily risen since 1970. By contrast, CBD concentrations have remained generally stable. High-potency cannabis products are common in both recreational and medicinal settings.

“For somebody prescribing medicinal cannabis that has a ≥10% concentration of THC, I’d be particularly wary of the risk of psychosis,” said Dr. Di Forti. “If you’re expecting people to use a high content of THC daily to medicate pain or a chronic condition, you even more so need to be aware that this is a potential side effect.”

Dr. Di Forti noted that her findings come from a cohort of recreational users, most of whom were aged 18-35 years.

“There have actually not been studies developed from collecting data in this area from groups specifically using cannabis for medicinal rather than recreational purposes,” she said.

She added that she personally has no concerns about the use of medical cannabis but wants clinicians to be aware of the risk for psychosis, to structure their patient conversations to identify risk factors or family histories of psychosis, and to become knowledgeable in detecting the often subtle signs of its initial onset.

When cannabis-associated psychosis occurs, Dr. Di Forti said it is primarily treated with conventional means, such as antipsychotics and therapeutic interventions and by refraining from using cannabis. Achieving the latter goal can be a challenge for patients who are daily users of high-potency cannabis. Currently, there are no treatment options such as those offered to patients withdrawing from the use of alcohol or opioids. Dr. Di Forti and colleagues are currently researching a solution to that problem through the use of another medical cannabis, the oromucosal spray Sativex, which has been approved in the European Union.
 

The regulatory obstacles to clarifying cannabis’ role in medicine

That currently there is limited or no evidence to support the use of medical cannabis for the treatment of neuropsychiatric conditions points to the inherent difficulties in conducting high-level research in this area.

“There’s a tremendous shortage of reliable data, largely due to regulatory barriers,” said Dr. Martinez.

Since 1970, cannabis has been listed as a Schedule I drug that is illegal to prescribe (the Agriculture Improvement Act of 2018 removed hemp from such restrictions). The FDA has issued guidance for researchers who wish to investigate treatments using Cannabis sativa or its derivatives in which the THC content is greater than 0.3%. Such research requires regular interactions with several federal agencies, including the Drug Enforcement Administration.

“It’s impossible to do multicenter RCTs with large numbers of patients, because you can’t transport cannabis across state lines,” said Dr. Wallace.

Regulatory restrictions regarding medical cannabis vary considerably throughout the world (the European Monitoring Center for Drugs and Drug Addiction provides a useful breakdown of this on their website). The lack of consistency in regulatory oversight acts as an impediment for conducting large-scale international multicenter studies on the topic.

Dr. Buhmann noted that, in Germany, cannabis has been broadly approved for treatment-resistant conditions with severe symptoms that impair quality of life. In addition, it is easy to be reimbursed for the use of cannabis as a medical treatment. These factors serve as disincentives for the funding of high-quality studies.

“It’s likely that no pharmaceutical company will do an expensive RCT to get an approval for Parkinson’s disease because it is already possible to prescribe medical cannabis of any type of THC-containing cannabinoid, dose, or route of application,” Dr. Buhmann said.

In the face of such restrictions and barriers, researchers are turning to ambitious real-world data projects to better understand medical cannabis’ efficacy and safety. A notable example is ProjectTwenty21, which is supported by the Royal College of Psychiatrists. The project is collecting outcomes of the use of medical cannabis among 20,000 U.K. patients whose conventional treatments of chronic pain, anxiety disorder, epilepsy, multiple sclerosis, PTSD, substance use disorder, and Tourette syndrome failed.

Dr. Freedman noted that the continued lack of high-quality data creates a void that commercial interests fill with unfounded claims.

“The danger is that patients might abandon a medication or intervention backed by robust science in favor of something without any science or evidence behind it,” he said. “There is no reason not to expect the same level of data for claims about cannabis products as we would expect from pharmaceutical products.”

Getting to that point, however, will require that the authorities governing clinical trials begin to view cannabis as the research community does, as a possible treatment with potential value, rather than as an illicit drug that needs to be tamped down.

A version of this article first appeared on Medscape.com.

Although the healing properties of cannabis have been touted for millennia, research into its potential neuropsychiatric applications truly began to take off in the 1990s following the discovery of the cannabinoid system in the brain. This led to speculation that cannabis could play a therapeutic role in regulating dopamine, serotonin, and other neurotransmitters and offer a new means of treating various ailments.

LPETTET/Getty Images

At the same time, efforts to liberalize marijuana laws have successfully played out in several nations, including the United States, where, as of April 29, 36 states provide some access to cannabis. These dual tracks – medical and political – have made cannabis an increasingly accepted part of the cultural fabric.

Yet with this development has come a new quandary for clinicians. Medical cannabis has been made widely available to patients and has largely outpaced the clinical evidence, leaving it unclear how and for which indications it should be used.
 

The many forms of medical cannabis

Cannabis is a genus of plants that includes marijuana (Cannabis sativa) and hemp. These plants contain over 100 compounds, including terpenes, flavonoids, and – most importantly for medicinal applications – cannabinoids.

The most abundant cannabinoid in marijuana is the psychotropic delta-9-tetrahydrocannabinol (THC), which imparts the “high” sensation. The next most abundant cannabinoid is cannabidiol (CBD), which is the nonpsychotropic. THC and CBD are the most extensively studied cannabinoids, together and in isolation. Evidence suggests that other cannabinoids and terpenoids may also hold medical promise and that cannabis’ various compounds can work synergistically to produce a so-called entourage effect.

Patients walking into a typical medical cannabis dispensary will be faced with several plant-derived and synthetic options, which can differ considerably in terms of the ratios and amounts of THC and CBD they contain, as well in how they are consumed (i.e., via smoke, vapor, ingestion, topical administration, or oromucosal spray), all of which can alter their effects. Further complicating matters is the varying level of oversight each state and country has in how and whether they test for and accurately label products’ potency, cannabinoid content, and possible impurities.

Medically authorized, prescription cannabis products go through an official regulatory review process, and indications/contraindications have been established for them. To date, the Food and Drug Administration has approved one cannabis-derived drug product – Epidiolex (purified CBD) – for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients aged 2 years and older. The FDA has also approved three synthetic cannabis-related drug products – Marinol, Syndros (or dronabinol, created from synthetic THC), and Cesamet (or nabilone, a synthetic cannabinoid similar to THC) – all of which are indicated for treatment-related nausea and anorexia associated with weight loss in AIDS patients.

Surveys of medical cannabis consumers indicate that most people cannot distinguish between THC and CBD, so the first role that physicians find themselves in when recommending this treatment may be in helping patients navigate the volume of options.
 

Promising treatment for pain

Chronic pain is the leading reason patients seek out medical cannabis. It is also the indication that most researchers agree has the strongest evidence to support its use.

“In my mind, the most promising immediate use for medical cannabis is with THC for pain,” Diana M. Martinez, MD, a professor of psychiatry at Columbia University, New York, who specializes in addiction research, said in a recent MDedge podcast. “THC could be added to the armamentarium of pain medications that we use today.”

In a 2015 systematic literature review, researchers assessed 28 randomized, controlled trials (RCTs) of the use of cannabinoids for chronic pain. They reported that a variety of formulations resulted in at least a 30% reduction in the odds of pain, compared with placebo. A meta-analysis of five RCTs involving patients with neuropathic pain found a 30% reduction in pain over placebo with inhaled, vaporized cannabis. Varying results have been reported in additional studies for this indication. The National Academies of Sciences, Engineering, and Medicine concluded that there was a substantial body of evidence that cannabis is an effective treatment for chronic pain in adults.

The ongoing opioid epidemic has lent these results additional relevance. Data indicate that patients with chronic pain who undergo treatment with medical cannabis can reduce their intake of opioids by more than 60%.

Seeing this firsthand has caused Mark Steven Wallace, MD, a pain management specialist and chair of the division of pain medicine at the University of California San Diego Health, to reconsider offering cannabis to his patients.

“I think it’s probably more efficacious, just from my personal experience, and it’s a much lower risk of abuse and dependence than the opioids,” he said.

Dr. Wallace advised that clinicians who treat pain consider the ratios of cannabinoids.

“This is anecdotal, but we do find that with the combination of the two, CBD reduces the psychoactive effects of the THC. The ratios we use during the daytime range around 20 mg of CBD to 1 mg of THC,” he said.

In a recent secondary analysis of an RCT involving patients with painful diabetic peripheral neuropathy, Dr. Wallace and colleagues showed that THC’s effects appear to reverse themselves at a certain level.

“As the THC level goes up, the pain reduces until you reach about 16 ng/mL; then it starts going in the opposite direction, and pain will start to increase,” he said. “Even recreational cannabis users have reported that they avoid high doses because it’s very aversive. Using cannabis is all about, start low and go slow.”
 

A mixed bag for neurologic indications

There are relatively limited data on the use of medical cannabis for other neurologic conditions, and results have varied. For uses other than pain management, the evidence that does exist is strongest regarding epilepsy, said Daniel Freedman, DO, assistant professor of neurology at the University of Texas at Austin. He noted “multiple high-quality RCTs showing that pharmaceutical-grade CBD can reduce seizures associated with two particular epilepsy syndromes: Dravet Syndrome and Lennox Gastaut.”

These findings led to the FDA’s 2018 approval of Epidiolex for these syndromes. In earlier years, interest in CBD for pediatric seizures was largely driven by anecdotal parental reports of its benefits. NASEM’s 2017 overview on medical cannabis found evidence from subsequent RCTs in this indication to be insufficient. Clinicians who prescribe CBD for this indication must be vigilant because it can interact with several commonly used antiepileptic drugs.

Cannabinoid treatments have also shown success in alleviating muscle spasticity resulting from multiple sclerosis, most prominently in the form of nabiximols (Sativex), a standardized oralmucosal spray containing approximately equal quantities of THC and CBD. Nabiximols is approved in Europe but not in the United States. Moderate evidence supports the efficacy of these and other treatments over placebo in reducing muscle spasticity. Patient ratings of its effects tend to be higher than clinician assessment.

Parkinson’s disease has not yet been approved as an indication for treatment with cannabis or cannabinoids, yet a growing body of preclinical data suggests these could influence the dopaminergic system, said Carsten Buhmann, MD, from the department of neurology at the University Medical Center Hamburg-Eppendorf (Germany).

“In general, cannabinoids modulate basal-ganglia function on two levels which are especially relevant in Parkinson’s disease, i.e., the glutamatergic/dopaminergic synaptic neurotransmission and the corticostriatal plasticity,” he said. “Furthermore, activation of the endocannabinoid system might induce neuroprotective effects related to direct receptor-independent mechanisms, activation of anti-inflammatory cascades in glial cells via the cannabinoid receptor type 2, and antiglutamatergic antiexcitotoxic properties.”

Dr. Buhmann said that currently, clinical evidence is scarce, consisting of only four double-blind, placebo-controlled RCTs involving 49 patients. Various cannabinoids and methods of administering treatment were employed. Improvement was only observed in one of these RCTs, which found that the cannabinoid receptor agonist nabilone significantly reduced levodopa-induced dyskinesia for patients with Parkinson’s disease. Subjective data support a beneficial effect. In a nationwide survey of 1,348 respondents conducted by Dr. Buhmann and colleagues, the majority of medical cannabis users reported that it improved their symptoms (54% with oral CBD and 68% with inhaled THC-containing cannabis).

NASEM concluded that there was insufficient evidence to support the efficacy of medical cannabis for other neurologic conditions, including Tourette syndrome, amyotrophic lateral sclerosis, Huntington disease, dystonia, or dementia. A 2020 position statement from the American Academy of Neurology cited the lack of sufficient peer-reviewed research as the reason it could not currently support the use of cannabis for neurologic disorders.

Yet, according to Dr. Freedman, who served as a coauthor of the AAN position statement, this hasn’t stymied research interest in the topic. He’s seen a substantial uptick in studies of CBD over the past 2 years. “The body of evidence grows, but I still see many claims being made without evidence. And no one seems to care about all the negative trials.”
 

Cannabis as a treatment for, and cause of, psychiatric disorders

Mental health problems – such as anxiety, depression, and PTSD – are among the most common reasons patients seek out medical cannabis. There is an understandable interest in using cannabis and cannabinoids to treat psychiatric disorders. Preclinical studies suggest that the endocannabinoid system plays a prominent role in modulating feelings of anxiety, mood, and fear. As with opioids and chronic pain management, there is hope that medical cannabis may provide a means of reducing prescription anxiolytics and their associated risks.

The authors of the first systematic review (BMC Psychiatry. 2020 Jan 16;20[1]:24) of the use of medical cannabis for major psychiatric disorders noted that the current evidence was “encouraging, albeit embryonic.”

Meta-analyses have indicated a small but positive association between cannabis use and anxiety, although this may reflect the fact that patients with anxiety sought out this treatment. Given the risks for substance use disorders among patients with anxiety, CBD may present a more viable option. Positive results have been shown as treatment for generalized social anxiety disorder.

Limited but encouraging results have also been reported regarding the alleviation of PTSD symptoms with both cannabis and CBD, although the body of high-quality evidence hasn’t notably progressed since 2017, when NASEM declared that the evidence was insufficient. Supportive evidence is similarly lacking regarding the treatment of depression. Longitudinal studies suggest that cannabis use, particularly heavy use, may increase the risk of developing this disorder. Because THC is psychoactive, it is advised that it be avoided by patients at risk for psychotic disorders. However, CBD has yielded limited benefits for patients with treatment-resistant schizophrenia and for young people at risk for psychosis.

The use of medical cannabis for psychiatric conditions requires a complex balancing act, inasmuch as these treatments may exacerbate the very problems they are intended to alleviate.

Marta Di Forti, MD, PhD, professor of psychiatric research at Kings College London, has been at the forefront of determining the mental health risks of continued cannabis use. In 2019, Dr. Di Forti developed the first and only Cannabis Clinic for Patients With Psychosis in London where she and her colleagues have continued to elucidate this connection.

Dr. Di Forti and colleagues have linked daily cannabis use to an increase in the risk of experiencing psychotic disorder, compared with never using it. That risk was further increased among users of high-potency cannabis (≥10% THC). The latter finding has troubling implications, because concentrations of THC have steadily risen since 1970. By contrast, CBD concentrations have remained generally stable. High-potency cannabis products are common in both recreational and medicinal settings.

“For somebody prescribing medicinal cannabis that has a ≥10% concentration of THC, I’d be particularly wary of the risk of psychosis,” said Dr. Di Forti. “If you’re expecting people to use a high content of THC daily to medicate pain or a chronic condition, you even more so need to be aware that this is a potential side effect.”

Dr. Di Forti noted that her findings come from a cohort of recreational users, most of whom were aged 18-35 years.

“There have actually not been studies developed from collecting data in this area from groups specifically using cannabis for medicinal rather than recreational purposes,” she said.

She added that she personally has no concerns about the use of medical cannabis but wants clinicians to be aware of the risk for psychosis, to structure their patient conversations to identify risk factors or family histories of psychosis, and to become knowledgeable in detecting the often subtle signs of its initial onset.

When cannabis-associated psychosis occurs, Dr. Di Forti said it is primarily treated with conventional means, such as antipsychotics and therapeutic interventions and by refraining from using cannabis. Achieving the latter goal can be a challenge for patients who are daily users of high-potency cannabis. Currently, there are no treatment options such as those offered to patients withdrawing from the use of alcohol or opioids. Dr. Di Forti and colleagues are currently researching a solution to that problem through the use of another medical cannabis, the oromucosal spray Sativex, which has been approved in the European Union.
 

The regulatory obstacles to clarifying cannabis’ role in medicine

That currently there is limited or no evidence to support the use of medical cannabis for the treatment of neuropsychiatric conditions points to the inherent difficulties in conducting high-level research in this area.

“There’s a tremendous shortage of reliable data, largely due to regulatory barriers,” said Dr. Martinez.

Since 1970, cannabis has been listed as a Schedule I drug that is illegal to prescribe (the Agriculture Improvement Act of 2018 removed hemp from such restrictions). The FDA has issued guidance for researchers who wish to investigate treatments using Cannabis sativa or its derivatives in which the THC content is greater than 0.3%. Such research requires regular interactions with several federal agencies, including the Drug Enforcement Administration.

“It’s impossible to do multicenter RCTs with large numbers of patients, because you can’t transport cannabis across state lines,” said Dr. Wallace.

Regulatory restrictions regarding medical cannabis vary considerably throughout the world (the European Monitoring Center for Drugs and Drug Addiction provides a useful breakdown of this on their website). The lack of consistency in regulatory oversight acts as an impediment for conducting large-scale international multicenter studies on the topic.

Dr. Buhmann noted that, in Germany, cannabis has been broadly approved for treatment-resistant conditions with severe symptoms that impair quality of life. In addition, it is easy to be reimbursed for the use of cannabis as a medical treatment. These factors serve as disincentives for the funding of high-quality studies.

“It’s likely that no pharmaceutical company will do an expensive RCT to get an approval for Parkinson’s disease because it is already possible to prescribe medical cannabis of any type of THC-containing cannabinoid, dose, or route of application,” Dr. Buhmann said.

In the face of such restrictions and barriers, researchers are turning to ambitious real-world data projects to better understand medical cannabis’ efficacy and safety. A notable example is ProjectTwenty21, which is supported by the Royal College of Psychiatrists. The project is collecting outcomes of the use of medical cannabis among 20,000 U.K. patients whose conventional treatments of chronic pain, anxiety disorder, epilepsy, multiple sclerosis, PTSD, substance use disorder, and Tourette syndrome failed.

Dr. Freedman noted that the continued lack of high-quality data creates a void that commercial interests fill with unfounded claims.

“The danger is that patients might abandon a medication or intervention backed by robust science in favor of something without any science or evidence behind it,” he said. “There is no reason not to expect the same level of data for claims about cannabis products as we would expect from pharmaceutical products.”

Getting to that point, however, will require that the authorities governing clinical trials begin to view cannabis as the research community does, as a possible treatment with potential value, rather than as an illicit drug that needs to be tamped down.

A version of this article first appeared on Medscape.com.

Although the healing properties of cannabis have been touted for millennia, research into its potential neuropsychiatric applications truly began to take off in the 1990s following the discovery of the cannabinoid system in the brain. This led to speculation that cannabis could play a therapeutic role in regulating dopamine, serotonin, and other neurotransmitters and offer a new means of treating various ailments.

LPETTET/Getty Images

At the same time, efforts to liberalize marijuana laws have successfully played out in several nations, including the United States, where, as of April 29, 36 states provide some access to cannabis. These dual tracks – medical and political – have made cannabis an increasingly accepted part of the cultural fabric.

Yet with this development has come a new quandary for clinicians. Medical cannabis has been made widely available to patients and has largely outpaced the clinical evidence, leaving it unclear how and for which indications it should be used.
 

The many forms of medical cannabis

Cannabis is a genus of plants that includes marijuana (Cannabis sativa) and hemp. These plants contain over 100 compounds, including terpenes, flavonoids, and – most importantly for medicinal applications – cannabinoids.

The most abundant cannabinoid in marijuana is the psychotropic delta-9-tetrahydrocannabinol (THC), which imparts the “high” sensation. The next most abundant cannabinoid is cannabidiol (CBD), which is the nonpsychotropic. THC and CBD are the most extensively studied cannabinoids, together and in isolation. Evidence suggests that other cannabinoids and terpenoids may also hold medical promise and that cannabis’ various compounds can work synergistically to produce a so-called entourage effect.

Patients walking into a typical medical cannabis dispensary will be faced with several plant-derived and synthetic options, which can differ considerably in terms of the ratios and amounts of THC and CBD they contain, as well in how they are consumed (i.e., via smoke, vapor, ingestion, topical administration, or oromucosal spray), all of which can alter their effects. Further complicating matters is the varying level of oversight each state and country has in how and whether they test for and accurately label products’ potency, cannabinoid content, and possible impurities.

Medically authorized, prescription cannabis products go through an official regulatory review process, and indications/contraindications have been established for them. To date, the Food and Drug Administration has approved one cannabis-derived drug product – Epidiolex (purified CBD) – for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients aged 2 years and older. The FDA has also approved three synthetic cannabis-related drug products – Marinol, Syndros (or dronabinol, created from synthetic THC), and Cesamet (or nabilone, a synthetic cannabinoid similar to THC) – all of which are indicated for treatment-related nausea and anorexia associated with weight loss in AIDS patients.

Surveys of medical cannabis consumers indicate that most people cannot distinguish between THC and CBD, so the first role that physicians find themselves in when recommending this treatment may be in helping patients navigate the volume of options.
 

Promising treatment for pain

Chronic pain is the leading reason patients seek out medical cannabis. It is also the indication that most researchers agree has the strongest evidence to support its use.

“In my mind, the most promising immediate use for medical cannabis is with THC for pain,” Diana M. Martinez, MD, a professor of psychiatry at Columbia University, New York, who specializes in addiction research, said in a recent MDedge podcast. “THC could be added to the armamentarium of pain medications that we use today.”

In a 2015 systematic literature review, researchers assessed 28 randomized, controlled trials (RCTs) of the use of cannabinoids for chronic pain. They reported that a variety of formulations resulted in at least a 30% reduction in the odds of pain, compared with placebo. A meta-analysis of five RCTs involving patients with neuropathic pain found a 30% reduction in pain over placebo with inhaled, vaporized cannabis. Varying results have been reported in additional studies for this indication. The National Academies of Sciences, Engineering, and Medicine concluded that there was a substantial body of evidence that cannabis is an effective treatment for chronic pain in adults.

The ongoing opioid epidemic has lent these results additional relevance. Data indicate that patients with chronic pain who undergo treatment with medical cannabis can reduce their intake of opioids by more than 60%.

Seeing this firsthand has caused Mark Steven Wallace, MD, a pain management specialist and chair of the division of pain medicine at the University of California San Diego Health, to reconsider offering cannabis to his patients.

“I think it’s probably more efficacious, just from my personal experience, and it’s a much lower risk of abuse and dependence than the opioids,” he said.

Dr. Wallace advised that clinicians who treat pain consider the ratios of cannabinoids.

“This is anecdotal, but we do find that with the combination of the two, CBD reduces the psychoactive effects of the THC. The ratios we use during the daytime range around 20 mg of CBD to 1 mg of THC,” he said.

In a recent secondary analysis of an RCT involving patients with painful diabetic peripheral neuropathy, Dr. Wallace and colleagues showed that THC’s effects appear to reverse themselves at a certain level.

“As the THC level goes up, the pain reduces until you reach about 16 ng/mL; then it starts going in the opposite direction, and pain will start to increase,” he said. “Even recreational cannabis users have reported that they avoid high doses because it’s very aversive. Using cannabis is all about, start low and go slow.”
 

A mixed bag for neurologic indications

There are relatively limited data on the use of medical cannabis for other neurologic conditions, and results have varied. For uses other than pain management, the evidence that does exist is strongest regarding epilepsy, said Daniel Freedman, DO, assistant professor of neurology at the University of Texas at Austin. He noted “multiple high-quality RCTs showing that pharmaceutical-grade CBD can reduce seizures associated with two particular epilepsy syndromes: Dravet Syndrome and Lennox Gastaut.”

These findings led to the FDA’s 2018 approval of Epidiolex for these syndromes. In earlier years, interest in CBD for pediatric seizures was largely driven by anecdotal parental reports of its benefits. NASEM’s 2017 overview on medical cannabis found evidence from subsequent RCTs in this indication to be insufficient. Clinicians who prescribe CBD for this indication must be vigilant because it can interact with several commonly used antiepileptic drugs.

Cannabinoid treatments have also shown success in alleviating muscle spasticity resulting from multiple sclerosis, most prominently in the form of nabiximols (Sativex), a standardized oralmucosal spray containing approximately equal quantities of THC and CBD. Nabiximols is approved in Europe but not in the United States. Moderate evidence supports the efficacy of these and other treatments over placebo in reducing muscle spasticity. Patient ratings of its effects tend to be higher than clinician assessment.

Parkinson’s disease has not yet been approved as an indication for treatment with cannabis or cannabinoids, yet a growing body of preclinical data suggests these could influence the dopaminergic system, said Carsten Buhmann, MD, from the department of neurology at the University Medical Center Hamburg-Eppendorf (Germany).

“In general, cannabinoids modulate basal-ganglia function on two levels which are especially relevant in Parkinson’s disease, i.e., the glutamatergic/dopaminergic synaptic neurotransmission and the corticostriatal plasticity,” he said. “Furthermore, activation of the endocannabinoid system might induce neuroprotective effects related to direct receptor-independent mechanisms, activation of anti-inflammatory cascades in glial cells via the cannabinoid receptor type 2, and antiglutamatergic antiexcitotoxic properties.”

Dr. Buhmann said that currently, clinical evidence is scarce, consisting of only four double-blind, placebo-controlled RCTs involving 49 patients. Various cannabinoids and methods of administering treatment were employed. Improvement was only observed in one of these RCTs, which found that the cannabinoid receptor agonist nabilone significantly reduced levodopa-induced dyskinesia for patients with Parkinson’s disease. Subjective data support a beneficial effect. In a nationwide survey of 1,348 respondents conducted by Dr. Buhmann and colleagues, the majority of medical cannabis users reported that it improved their symptoms (54% with oral CBD and 68% with inhaled THC-containing cannabis).

NASEM concluded that there was insufficient evidence to support the efficacy of medical cannabis for other neurologic conditions, including Tourette syndrome, amyotrophic lateral sclerosis, Huntington disease, dystonia, or dementia. A 2020 position statement from the American Academy of Neurology cited the lack of sufficient peer-reviewed research as the reason it could not currently support the use of cannabis for neurologic disorders.

Yet, according to Dr. Freedman, who served as a coauthor of the AAN position statement, this hasn’t stymied research interest in the topic. He’s seen a substantial uptick in studies of CBD over the past 2 years. “The body of evidence grows, but I still see many claims being made without evidence. And no one seems to care about all the negative trials.”
 

Cannabis as a treatment for, and cause of, psychiatric disorders

Mental health problems – such as anxiety, depression, and PTSD – are among the most common reasons patients seek out medical cannabis. There is an understandable interest in using cannabis and cannabinoids to treat psychiatric disorders. Preclinical studies suggest that the endocannabinoid system plays a prominent role in modulating feelings of anxiety, mood, and fear. As with opioids and chronic pain management, there is hope that medical cannabis may provide a means of reducing prescription anxiolytics and their associated risks.

The authors of the first systematic review (BMC Psychiatry. 2020 Jan 16;20[1]:24) of the use of medical cannabis for major psychiatric disorders noted that the current evidence was “encouraging, albeit embryonic.”

Meta-analyses have indicated a small but positive association between cannabis use and anxiety, although this may reflect the fact that patients with anxiety sought out this treatment. Given the risks for substance use disorders among patients with anxiety, CBD may present a more viable option. Positive results have been shown as treatment for generalized social anxiety disorder.

Limited but encouraging results have also been reported regarding the alleviation of PTSD symptoms with both cannabis and CBD, although the body of high-quality evidence hasn’t notably progressed since 2017, when NASEM declared that the evidence was insufficient. Supportive evidence is similarly lacking regarding the treatment of depression. Longitudinal studies suggest that cannabis use, particularly heavy use, may increase the risk of developing this disorder. Because THC is psychoactive, it is advised that it be avoided by patients at risk for psychotic disorders. However, CBD has yielded limited benefits for patients with treatment-resistant schizophrenia and for young people at risk for psychosis.

The use of medical cannabis for psychiatric conditions requires a complex balancing act, inasmuch as these treatments may exacerbate the very problems they are intended to alleviate.

Marta Di Forti, MD, PhD, professor of psychiatric research at Kings College London, has been at the forefront of determining the mental health risks of continued cannabis use. In 2019, Dr. Di Forti developed the first and only Cannabis Clinic for Patients With Psychosis in London where she and her colleagues have continued to elucidate this connection.

Dr. Di Forti and colleagues have linked daily cannabis use to an increase in the risk of experiencing psychotic disorder, compared with never using it. That risk was further increased among users of high-potency cannabis (≥10% THC). The latter finding has troubling implications, because concentrations of THC have steadily risen since 1970. By contrast, CBD concentrations have remained generally stable. High-potency cannabis products are common in both recreational and medicinal settings.

“For somebody prescribing medicinal cannabis that has a ≥10% concentration of THC, I’d be particularly wary of the risk of psychosis,” said Dr. Di Forti. “If you’re expecting people to use a high content of THC daily to medicate pain or a chronic condition, you even more so need to be aware that this is a potential side effect.”

Dr. Di Forti noted that her findings come from a cohort of recreational users, most of whom were aged 18-35 years.

“There have actually not been studies developed from collecting data in this area from groups specifically using cannabis for medicinal rather than recreational purposes,” she said.

She added that she personally has no concerns about the use of medical cannabis but wants clinicians to be aware of the risk for psychosis, to structure their patient conversations to identify risk factors or family histories of psychosis, and to become knowledgeable in detecting the often subtle signs of its initial onset.

When cannabis-associated psychosis occurs, Dr. Di Forti said it is primarily treated with conventional means, such as antipsychotics and therapeutic interventions and by refraining from using cannabis. Achieving the latter goal can be a challenge for patients who are daily users of high-potency cannabis. Currently, there are no treatment options such as those offered to patients withdrawing from the use of alcohol or opioids. Dr. Di Forti and colleagues are currently researching a solution to that problem through the use of another medical cannabis, the oromucosal spray Sativex, which has been approved in the European Union.
 

The regulatory obstacles to clarifying cannabis’ role in medicine

That currently there is limited or no evidence to support the use of medical cannabis for the treatment of neuropsychiatric conditions points to the inherent difficulties in conducting high-level research in this area.

“There’s a tremendous shortage of reliable data, largely due to regulatory barriers,” said Dr. Martinez.

Since 1970, cannabis has been listed as a Schedule I drug that is illegal to prescribe (the Agriculture Improvement Act of 2018 removed hemp from such restrictions). The FDA has issued guidance for researchers who wish to investigate treatments using Cannabis sativa or its derivatives in which the THC content is greater than 0.3%. Such research requires regular interactions with several federal agencies, including the Drug Enforcement Administration.

“It’s impossible to do multicenter RCTs with large numbers of patients, because you can’t transport cannabis across state lines,” said Dr. Wallace.

Regulatory restrictions regarding medical cannabis vary considerably throughout the world (the European Monitoring Center for Drugs and Drug Addiction provides a useful breakdown of this on their website). The lack of consistency in regulatory oversight acts as an impediment for conducting large-scale international multicenter studies on the topic.

Dr. Buhmann noted that, in Germany, cannabis has been broadly approved for treatment-resistant conditions with severe symptoms that impair quality of life. In addition, it is easy to be reimbursed for the use of cannabis as a medical treatment. These factors serve as disincentives for the funding of high-quality studies.

“It’s likely that no pharmaceutical company will do an expensive RCT to get an approval for Parkinson’s disease because it is already possible to prescribe medical cannabis of any type of THC-containing cannabinoid, dose, or route of application,” Dr. Buhmann said.

In the face of such restrictions and barriers, researchers are turning to ambitious real-world data projects to better understand medical cannabis’ efficacy and safety. A notable example is ProjectTwenty21, which is supported by the Royal College of Psychiatrists. The project is collecting outcomes of the use of medical cannabis among 20,000 U.K. patients whose conventional treatments of chronic pain, anxiety disorder, epilepsy, multiple sclerosis, PTSD, substance use disorder, and Tourette syndrome failed.

Dr. Freedman noted that the continued lack of high-quality data creates a void that commercial interests fill with unfounded claims.

“The danger is that patients might abandon a medication or intervention backed by robust science in favor of something without any science or evidence behind it,” he said. “There is no reason not to expect the same level of data for claims about cannabis products as we would expect from pharmaceutical products.”

Getting to that point, however, will require that the authorities governing clinical trials begin to view cannabis as the research community does, as a possible treatment with potential value, rather than as an illicit drug that needs to be tamped down.

A version of this article first appeared on Medscape.com.

COVID-19 and its resulting lockdowns are linked to posttraumatic stress disorder symptoms and other adverse outcomes among patients with eating disorders (EDs), two new studies show.

Courtesy Bill Branson/National Cancer Institute

Results of the first study show that patients with EDs had more stress, anxiety, depression, and PTSD-related symptoms during the lockdowns than their mentally healthy peers.

In the second study, treatment-related symptom improvement among patients with bulimia nervosa (BN) slowed following lockdown. In addition, patients with BN or anorexia nervosa (AN) experienced significant worsening of disorder-specific behaviors, including binge eating and overexercising.

Because of the strict lockdown measures introduced by the Italian government to contain the COVID-19 pandemic, “everyday life of all citizens was disrupted,” Veronica Nisticò, MS, Università Degli Studi Di Milano, who led the first study, told delegates attending the virtual European Psychiatric Association 2021 Congress.

In addition to difficulties in accessing health care, “it became difficult to go to the supermarket, to the gym, and to have the social support we were all used to,” all of which had a well-documented impact on mental health, added Ms. Nisticò, who is also affiliated with Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics.
 

Loss of control

Previous research suggests that individuals with EDs experience high levels of anxiety and an increase in binge eating, exercise, and purging behaviors, said Ms. Nisticò.

To investigate further, the researchers conducted a longitudinal study of the changes in prevalence of adverse outcomes. In the study, two assessments were conducted.

In the first assessment, conducted in April 2020, the researchers assessed 59 outpatients with EDs and 43 unaffected hospital staff and their acquaintances. The second group served as the control group.

Participants completed an online survey that included several standardized depression and anxiety scales, as well as an ad hoc survey adapted from the Eating Disorder Examination Questionnaire. This assessed changes in restrictive dieting, control over food, body image, and psychological well-being in comparison with prepandemic levels.

The results, which were also recently published online in Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, showed that patients with EDs experienced significantly more stress, anxiety, depression, and PTSD-related symptoms in comparison with control persons (P < .05 for all).

In addition, the investigators found that those with EDs were more fearful of losing control over their eating behavior, spent more time thinking about food and their body, and became more uncomfortable seeing their body than before the lockdown in comparison with those without EDs (P < .05).
 

Clinical implications

A second assessment, which occurred in June 2020, after lockdown restrictions were lifted, included 40 patients with EDs who had taken part in the first assessment. This time, participants were asked to compare their current eating behavior with their eating behavior during the lockdown.

Although the lifting of lockdown restrictions was associated with significant improvement in PTSD-related symptoms, the impact on stress, anxiety, and depression persisted.

These findings, said Ms. Nisticó, support the hypothesis that specific conditions that occurred during the lockdown had a direct effect on specific ED symptoms.

These findings, she added, should be considered when developing interventions for EDs in the context of individual psychotherapy and when designing large, preventive interventions.

In the second study, Eleonora Rossi, MD, psychiatric unit, department of health sciences, University of Florence (Italy), and colleagues examined the longitudinal impact of the pandemic on individuals with EDs.

They examined 74 patients with AN or BN who had undergone baseline assessments and had completed a number of questionnaires in the first months of 2019 in conjunction with being enrolled in another study.

Participants were treated with enhanced cognitive-behavioral therapy and were reevaluated between November 2019 and January 2020. They were then compared with 97 healthy individuals.
 

Bulimia patients more vulnerable

After the outbreak of the pandemic, most treatment was administered online, so patients were able to continue therapy, Dr. Rossi said during her presentation.

All participants were assessed again in April 2020, 6 weeks after the start of Italy’s lockdown.

The results, which were published in the International Journal of Eating Disorders, show that the patients with EDs “underwent a significant improvement in terms of general and eating disorder specific psychopathology” during the first treatment period, Dr. Rossi reported. In addition, among those with AN, body mass index increased significantly (P < .05 for all).

Patients with AN continued to improve during the lockdown when therapy was administered online. However, improvements that had occurred among those with BN slowed, Dr. Rossi noted.

In addition, both groups of patients with EDs experienced a worsening of their pathological eating behaviors during the lockdown, in particular, objective binge eating and compensatory physical exercise (P < .05).

“Indeed, the positive trajectory of improvement observed before lockdown was clearly interrupted during the pandemic period,” Dr. Rossi said. This could “represent a possible hint of an imminent exacerbation of the disease.”

The results also suggest that the occurrence of arguments within the household and fear regarding the safety of loved ones predicted an increase in symptoms during the lockdown, she added.

In addition, patients with BN reported more severe COVID-related PTSD symptoms than did those with AN and the control group. This increase in severity of symptoms was more prevalent among patients who had a history of childhood trauma and among those with insecure attachment, suggesting that such patients may be more vulnerable.
 

Evidence of recovery

Commenting on the studies, David Spiegel, MD, associate chair of psychiatry, Stanford (Calif.) University, noted that EDs commonly occur after physical or sexual trauma earlier in life.

“It’s a standard thing with trauma-related disorders that any other, even relatively minor, traumatic experience can exacerbate PTSD symptoms,” said Dr. Spiegel, who was not involved in the studies. In addition, the trauma of the COVID pandemic “was not minor.

“The relative isolation and the lack of outside contact may focus many people with eating disorders even more on their struggles with how they are taking care of their bodies,” said Dr. Spiegel.

“It struck me that the anorexia nervosa group were more impervious than the bulimia nervosa group, but I think that’s the case with the disorder. In some ways it’s more severe, obviously a more life-threatening disorder,” he added.

The “hopeful thing is that there seemed to be some evidence of recovery and improvement, particularly with the posttraumatic stress exacerbation, as time went on,” Dr. Spiegel said, “and that’s a good thing.”

The study authors and Dr. Spiegel reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

COVID-19 and its resulting lockdowns are linked to posttraumatic stress disorder symptoms and other adverse outcomes among patients with eating disorders (EDs), two new studies show.

Courtesy Bill Branson/National Cancer Institute

Results of the first study show that patients with EDs had more stress, anxiety, depression, and PTSD-related symptoms during the lockdowns than their mentally healthy peers.

In the second study, treatment-related symptom improvement among patients with bulimia nervosa (BN) slowed following lockdown. In addition, patients with BN or anorexia nervosa (AN) experienced significant worsening of disorder-specific behaviors, including binge eating and overexercising.

Because of the strict lockdown measures introduced by the Italian government to contain the COVID-19 pandemic, “everyday life of all citizens was disrupted,” Veronica Nisticò, MS, Università Degli Studi Di Milano, who led the first study, told delegates attending the virtual European Psychiatric Association 2021 Congress.

In addition to difficulties in accessing health care, “it became difficult to go to the supermarket, to the gym, and to have the social support we were all used to,” all of which had a well-documented impact on mental health, added Ms. Nisticò, who is also affiliated with Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics.
 

Loss of control

Previous research suggests that individuals with EDs experience high levels of anxiety and an increase in binge eating, exercise, and purging behaviors, said Ms. Nisticò.

To investigate further, the researchers conducted a longitudinal study of the changes in prevalence of adverse outcomes. In the study, two assessments were conducted.

In the first assessment, conducted in April 2020, the researchers assessed 59 outpatients with EDs and 43 unaffected hospital staff and their acquaintances. The second group served as the control group.

Participants completed an online survey that included several standardized depression and anxiety scales, as well as an ad hoc survey adapted from the Eating Disorder Examination Questionnaire. This assessed changes in restrictive dieting, control over food, body image, and psychological well-being in comparison with prepandemic levels.

The results, which were also recently published online in Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, showed that patients with EDs experienced significantly more stress, anxiety, depression, and PTSD-related symptoms in comparison with control persons (P < .05 for all).

In addition, the investigators found that those with EDs were more fearful of losing control over their eating behavior, spent more time thinking about food and their body, and became more uncomfortable seeing their body than before the lockdown in comparison with those without EDs (P < .05).
 

Clinical implications

A second assessment, which occurred in June 2020, after lockdown restrictions were lifted, included 40 patients with EDs who had taken part in the first assessment. This time, participants were asked to compare their current eating behavior with their eating behavior during the lockdown.

Although the lifting of lockdown restrictions was associated with significant improvement in PTSD-related symptoms, the impact on stress, anxiety, and depression persisted.

These findings, said Ms. Nisticó, support the hypothesis that specific conditions that occurred during the lockdown had a direct effect on specific ED symptoms.

These findings, she added, should be considered when developing interventions for EDs in the context of individual psychotherapy and when designing large, preventive interventions.

In the second study, Eleonora Rossi, MD, psychiatric unit, department of health sciences, University of Florence (Italy), and colleagues examined the longitudinal impact of the pandemic on individuals with EDs.

They examined 74 patients with AN or BN who had undergone baseline assessments and had completed a number of questionnaires in the first months of 2019 in conjunction with being enrolled in another study.

Participants were treated with enhanced cognitive-behavioral therapy and were reevaluated between November 2019 and January 2020. They were then compared with 97 healthy individuals.
 

Bulimia patients more vulnerable

After the outbreak of the pandemic, most treatment was administered online, so patients were able to continue therapy, Dr. Rossi said during her presentation.

All participants were assessed again in April 2020, 6 weeks after the start of Italy’s lockdown.

The results, which were published in the International Journal of Eating Disorders, show that the patients with EDs “underwent a significant improvement in terms of general and eating disorder specific psychopathology” during the first treatment period, Dr. Rossi reported. In addition, among those with AN, body mass index increased significantly (P < .05 for all).

Patients with AN continued to improve during the lockdown when therapy was administered online. However, improvements that had occurred among those with BN slowed, Dr. Rossi noted.

In addition, both groups of patients with EDs experienced a worsening of their pathological eating behaviors during the lockdown, in particular, objective binge eating and compensatory physical exercise (P < .05).

“Indeed, the positive trajectory of improvement observed before lockdown was clearly interrupted during the pandemic period,” Dr. Rossi said. This could “represent a possible hint of an imminent exacerbation of the disease.”

The results also suggest that the occurrence of arguments within the household and fear regarding the safety of loved ones predicted an increase in symptoms during the lockdown, she added.

In addition, patients with BN reported more severe COVID-related PTSD symptoms than did those with AN and the control group. This increase in severity of symptoms was more prevalent among patients who had a history of childhood trauma and among those with insecure attachment, suggesting that such patients may be more vulnerable.
 

Evidence of recovery

Commenting on the studies, David Spiegel, MD, associate chair of psychiatry, Stanford (Calif.) University, noted that EDs commonly occur after physical or sexual trauma earlier in life.

“It’s a standard thing with trauma-related disorders that any other, even relatively minor, traumatic experience can exacerbate PTSD symptoms,” said Dr. Spiegel, who was not involved in the studies. In addition, the trauma of the COVID pandemic “was not minor.

“The relative isolation and the lack of outside contact may focus many people with eating disorders even more on their struggles with how they are taking care of their bodies,” said Dr. Spiegel.

“It struck me that the anorexia nervosa group were more impervious than the bulimia nervosa group, but I think that’s the case with the disorder. In some ways it’s more severe, obviously a more life-threatening disorder,” he added.

The “hopeful thing is that there seemed to be some evidence of recovery and improvement, particularly with the posttraumatic stress exacerbation, as time went on,” Dr. Spiegel said, “and that’s a good thing.”

The study authors and Dr. Spiegel reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

COVID-19 and its resulting lockdowns are linked to posttraumatic stress disorder symptoms and other adverse outcomes among patients with eating disorders (EDs), two new studies show.

Courtesy Bill Branson/National Cancer Institute

Results of the first study show that patients with EDs had more stress, anxiety, depression, and PTSD-related symptoms during the lockdowns than their mentally healthy peers.

In the second study, treatment-related symptom improvement among patients with bulimia nervosa (BN) slowed following lockdown. In addition, patients with BN or anorexia nervosa (AN) experienced significant worsening of disorder-specific behaviors, including binge eating and overexercising.

Because of the strict lockdown measures introduced by the Italian government to contain the COVID-19 pandemic, “everyday life of all citizens was disrupted,” Veronica Nisticò, MS, Università Degli Studi Di Milano, who led the first study, told delegates attending the virtual European Psychiatric Association 2021 Congress.

In addition to difficulties in accessing health care, “it became difficult to go to the supermarket, to the gym, and to have the social support we were all used to,” all of which had a well-documented impact on mental health, added Ms. Nisticò, who is also affiliated with Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics.
 

Loss of control

Previous research suggests that individuals with EDs experience high levels of anxiety and an increase in binge eating, exercise, and purging behaviors, said Ms. Nisticò.

To investigate further, the researchers conducted a longitudinal study of the changes in prevalence of adverse outcomes. In the study, two assessments were conducted.

In the first assessment, conducted in April 2020, the researchers assessed 59 outpatients with EDs and 43 unaffected hospital staff and their acquaintances. The second group served as the control group.

Participants completed an online survey that included several standardized depression and anxiety scales, as well as an ad hoc survey adapted from the Eating Disorder Examination Questionnaire. This assessed changes in restrictive dieting, control over food, body image, and psychological well-being in comparison with prepandemic levels.

The results, which were also recently published online in Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, showed that patients with EDs experienced significantly more stress, anxiety, depression, and PTSD-related symptoms in comparison with control persons (P < .05 for all).

In addition, the investigators found that those with EDs were more fearful of losing control over their eating behavior, spent more time thinking about food and their body, and became more uncomfortable seeing their body than before the lockdown in comparison with those without EDs (P < .05).
 

Clinical implications

A second assessment, which occurred in June 2020, after lockdown restrictions were lifted, included 40 patients with EDs who had taken part in the first assessment. This time, participants were asked to compare their current eating behavior with their eating behavior during the lockdown.

Although the lifting of lockdown restrictions was associated with significant improvement in PTSD-related symptoms, the impact on stress, anxiety, and depression persisted.

These findings, said Ms. Nisticó, support the hypothesis that specific conditions that occurred during the lockdown had a direct effect on specific ED symptoms.

These findings, she added, should be considered when developing interventions for EDs in the context of individual psychotherapy and when designing large, preventive interventions.

In the second study, Eleonora Rossi, MD, psychiatric unit, department of health sciences, University of Florence (Italy), and colleagues examined the longitudinal impact of the pandemic on individuals with EDs.

They examined 74 patients with AN or BN who had undergone baseline assessments and had completed a number of questionnaires in the first months of 2019 in conjunction with being enrolled in another study.

Participants were treated with enhanced cognitive-behavioral therapy and were reevaluated between November 2019 and January 2020. They were then compared with 97 healthy individuals.
 

Bulimia patients more vulnerable

After the outbreak of the pandemic, most treatment was administered online, so patients were able to continue therapy, Dr. Rossi said during her presentation.

All participants were assessed again in April 2020, 6 weeks after the start of Italy’s lockdown.

The results, which were published in the International Journal of Eating Disorders, show that the patients with EDs “underwent a significant improvement in terms of general and eating disorder specific psychopathology” during the first treatment period, Dr. Rossi reported. In addition, among those with AN, body mass index increased significantly (P < .05 for all).

Patients with AN continued to improve during the lockdown when therapy was administered online. However, improvements that had occurred among those with BN slowed, Dr. Rossi noted.

In addition, both groups of patients with EDs experienced a worsening of their pathological eating behaviors during the lockdown, in particular, objective binge eating and compensatory physical exercise (P < .05).

“Indeed, the positive trajectory of improvement observed before lockdown was clearly interrupted during the pandemic period,” Dr. Rossi said. This could “represent a possible hint of an imminent exacerbation of the disease.”

The results also suggest that the occurrence of arguments within the household and fear regarding the safety of loved ones predicted an increase in symptoms during the lockdown, she added.

In addition, patients with BN reported more severe COVID-related PTSD symptoms than did those with AN and the control group. This increase in severity of symptoms was more prevalent among patients who had a history of childhood trauma and among those with insecure attachment, suggesting that such patients may be more vulnerable.
 

Evidence of recovery

Commenting on the studies, David Spiegel, MD, associate chair of psychiatry, Stanford (Calif.) University, noted that EDs commonly occur after physical or sexual trauma earlier in life.

“It’s a standard thing with trauma-related disorders that any other, even relatively minor, traumatic experience can exacerbate PTSD symptoms,” said Dr. Spiegel, who was not involved in the studies. In addition, the trauma of the COVID pandemic “was not minor.

“The relative isolation and the lack of outside contact may focus many people with eating disorders even more on their struggles with how they are taking care of their bodies,” said Dr. Spiegel.

“It struck me that the anorexia nervosa group were more impervious than the bulimia nervosa group, but I think that’s the case with the disorder. In some ways it’s more severe, obviously a more life-threatening disorder,” he added.

The “hopeful thing is that there seemed to be some evidence of recovery and improvement, particularly with the posttraumatic stress exacerbation, as time went on,” Dr. Spiegel said, “and that’s a good thing.”

The study authors and Dr. Spiegel reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

I woke up from a nap on Tuesday, April 20, to a barrage of text messages and social media alerts about the Derek Chauvin verdict. Messages varied in content, from “let’s celebrate,” to “just so exciting,” to “finally.” As I took in the sentiments of others, I could barely sense what, if any, sentiments I had of my own.

There I sat, a Black DEI [diversity, equity, and inclusion] consultant who calls herself a “psychiatrist-activist,” but slept through the landmark court decision for policing African Americans and felt almost nothing about it.

However, I did have feelings about other matters such as the slide decks due for my client, sending reassuring text messages about the hospitalization of a friend’s child, and the 2 weeks of patient notes on my to-do list. So why did I feel emotionally flatlined about an issue that should stimulate the opposite – emotional intensity?

The answer to “why” could be attributed to a number of psychological buzz words like trauma, grief, desensitization, dissociation, numbness, or my new favorite term, languishing.

Despite the applicability of any of the above, I think my emotional flattening has more to do with the fact that in addition to the guilty verdict, I also woke up to news that 16-year-old Ma’Khia Bryant had been shot by a police officer in Columbus, Ohio.

I asked myself: How can anyone find time to grieve, nevertheless celebrate when (young) Black people continue to be killed by the police?

While it hurts to see individuals who look like me being shot by police, or even emboldened citizens, my hurt likely pales in comparison to someone who grew up surrounded by police gun violence. I grew up solidly middle class, lived in a house at the end of a cul-de-sac in a semi-gated community, and have many years ahead of me to reach my earning potential as a physician in one of the most liberal cities in the nation. While I have the skin color that puts me at risk of being shot by police due to racism, I am in a cushy position compared to other Black people who live in cities or neighborhoods with more police shootings.

Given this line of thinking, it seems clearer to me why I do not feel like celebrating, but instead, feel grateful to be alive. Not only do I feel grateful to be alive, but alive with the emotional stamina to help White people understand their contributions to the widespread oppression that keeps our society rooted in white supremacy.

This brings me to my point of what I want people, especially physicians, to know about the guilty verdict of Derek Chauvin: Some of us cannot really celebrate until there is actual police reform. This is not to say that anyone is wrong to celebrate, as long as there is an understanding that a landmark court decision can represent a drop in the bucket for Black and Brown people who risk being shot by the police while unarmed just for being Black or Brown.

Meanwhile, White men like Kyle Rittenhouse who are peaceably arrested after shooting a man with a semi-automatic weapon receive donations from a Virginia police lieutenant; a policeman who, in a possible world, could one day pull me over while driving through Virginia given its proximity to Washington D.C., where I currently live.

Black and Brown people cannot fully celebrate until there is actual police reform, and reform across American institutions like the health care system. Celebration comes when the leaders who run schools, hospitals, and courtrooms look more like the numbers actually reflected in U.S. racial demographics and look less like Derek Chauvin.

Until there are more doctors who look like the racial breakdown of the nation, Black and Brown patients can never fully trust their primary care doctors, orthopedic surgeons, and psychiatrists who are White. While this reality may sound harsh, it is the reality for many of us who are dealing with trauma, grief, desensitization, dissociation, emotional numbness, or languishment resulting from racist experiences.

People of color cannot and will not stop protesting in the streets, being the one who always brings up race in the meeting, or disagreeing that the new changes are “not enough” until there is actual anti-racist institutional reform. More importantly, the efforts of people of color can be made more powerful working collectively with White allies.

But we need White allies who recognize their tendency to perceive “progress” in racial equality. We need White allies who recognize that despite the passage of the Civil Rights Act, the two-time election of a Black president, and the guilty verdict of Derek Chauvin, there is still so much work to do.
 

Dr. Cyrus is assistant professor in the department of psychiatry at Johns Hopkins University, Baltimore. She reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

I woke up from a nap on Tuesday, April 20, to a barrage of text messages and social media alerts about the Derek Chauvin verdict. Messages varied in content, from “let’s celebrate,” to “just so exciting,” to “finally.” As I took in the sentiments of others, I could barely sense what, if any, sentiments I had of my own.

There I sat, a Black DEI [diversity, equity, and inclusion] consultant who calls herself a “psychiatrist-activist,” but slept through the landmark court decision for policing African Americans and felt almost nothing about it.

However, I did have feelings about other matters such as the slide decks due for my client, sending reassuring text messages about the hospitalization of a friend’s child, and the 2 weeks of patient notes on my to-do list. So why did I feel emotionally flatlined about an issue that should stimulate the opposite – emotional intensity?

The answer to “why” could be attributed to a number of psychological buzz words like trauma, grief, desensitization, dissociation, numbness, or my new favorite term, languishing.

Despite the applicability of any of the above, I think my emotional flattening has more to do with the fact that in addition to the guilty verdict, I also woke up to news that 16-year-old Ma’Khia Bryant had been shot by a police officer in Columbus, Ohio.

I asked myself: How can anyone find time to grieve, nevertheless celebrate when (young) Black people continue to be killed by the police?

While it hurts to see individuals who look like me being shot by police, or even emboldened citizens, my hurt likely pales in comparison to someone who grew up surrounded by police gun violence. I grew up solidly middle class, lived in a house at the end of a cul-de-sac in a semi-gated community, and have many years ahead of me to reach my earning potential as a physician in one of the most liberal cities in the nation. While I have the skin color that puts me at risk of being shot by police due to racism, I am in a cushy position compared to other Black people who live in cities or neighborhoods with more police shootings.

Given this line of thinking, it seems clearer to me why I do not feel like celebrating, but instead, feel grateful to be alive. Not only do I feel grateful to be alive, but alive with the emotional stamina to help White people understand their contributions to the widespread oppression that keeps our society rooted in white supremacy.

This brings me to my point of what I want people, especially physicians, to know about the guilty verdict of Derek Chauvin: Some of us cannot really celebrate until there is actual police reform. This is not to say that anyone is wrong to celebrate, as long as there is an understanding that a landmark court decision can represent a drop in the bucket for Black and Brown people who risk being shot by the police while unarmed just for being Black or Brown.

Meanwhile, White men like Kyle Rittenhouse who are peaceably arrested after shooting a man with a semi-automatic weapon receive donations from a Virginia police lieutenant; a policeman who, in a possible world, could one day pull me over while driving through Virginia given its proximity to Washington D.C., where I currently live.

Black and Brown people cannot fully celebrate until there is actual police reform, and reform across American institutions like the health care system. Celebration comes when the leaders who run schools, hospitals, and courtrooms look more like the numbers actually reflected in U.S. racial demographics and look less like Derek Chauvin.

Until there are more doctors who look like the racial breakdown of the nation, Black and Brown patients can never fully trust their primary care doctors, orthopedic surgeons, and psychiatrists who are White. While this reality may sound harsh, it is the reality for many of us who are dealing with trauma, grief, desensitization, dissociation, emotional numbness, or languishment resulting from racist experiences.

People of color cannot and will not stop protesting in the streets, being the one who always brings up race in the meeting, or disagreeing that the new changes are “not enough” until there is actual anti-racist institutional reform. More importantly, the efforts of people of color can be made more powerful working collectively with White allies.

But we need White allies who recognize their tendency to perceive “progress” in racial equality. We need White allies who recognize that despite the passage of the Civil Rights Act, the two-time election of a Black president, and the guilty verdict of Derek Chauvin, there is still so much work to do.
 

Dr. Cyrus is assistant professor in the department of psychiatry at Johns Hopkins University, Baltimore. She reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

I woke up from a nap on Tuesday, April 20, to a barrage of text messages and social media alerts about the Derek Chauvin verdict. Messages varied in content, from “let’s celebrate,” to “just so exciting,” to “finally.” As I took in the sentiments of others, I could barely sense what, if any, sentiments I had of my own.

There I sat, a Black DEI [diversity, equity, and inclusion] consultant who calls herself a “psychiatrist-activist,” but slept through the landmark court decision for policing African Americans and felt almost nothing about it.

However, I did have feelings about other matters such as the slide decks due for my client, sending reassuring text messages about the hospitalization of a friend’s child, and the 2 weeks of patient notes on my to-do list. So why did I feel emotionally flatlined about an issue that should stimulate the opposite – emotional intensity?

The answer to “why” could be attributed to a number of psychological buzz words like trauma, grief, desensitization, dissociation, numbness, or my new favorite term, languishing.

Despite the applicability of any of the above, I think my emotional flattening has more to do with the fact that in addition to the guilty verdict, I also woke up to news that 16-year-old Ma’Khia Bryant had been shot by a police officer in Columbus, Ohio.

I asked myself: How can anyone find time to grieve, nevertheless celebrate when (young) Black people continue to be killed by the police?

While it hurts to see individuals who look like me being shot by police, or even emboldened citizens, my hurt likely pales in comparison to someone who grew up surrounded by police gun violence. I grew up solidly middle class, lived in a house at the end of a cul-de-sac in a semi-gated community, and have many years ahead of me to reach my earning potential as a physician in one of the most liberal cities in the nation. While I have the skin color that puts me at risk of being shot by police due to racism, I am in a cushy position compared to other Black people who live in cities or neighborhoods with more police shootings.

Given this line of thinking, it seems clearer to me why I do not feel like celebrating, but instead, feel grateful to be alive. Not only do I feel grateful to be alive, but alive with the emotional stamina to help White people understand their contributions to the widespread oppression that keeps our society rooted in white supremacy.

This brings me to my point of what I want people, especially physicians, to know about the guilty verdict of Derek Chauvin: Some of us cannot really celebrate until there is actual police reform. This is not to say that anyone is wrong to celebrate, as long as there is an understanding that a landmark court decision can represent a drop in the bucket for Black and Brown people who risk being shot by the police while unarmed just for being Black or Brown.

Meanwhile, White men like Kyle Rittenhouse who are peaceably arrested after shooting a man with a semi-automatic weapon receive donations from a Virginia police lieutenant; a policeman who, in a possible world, could one day pull me over while driving through Virginia given its proximity to Washington D.C., where I currently live.

Black and Brown people cannot fully celebrate until there is actual police reform, and reform across American institutions like the health care system. Celebration comes when the leaders who run schools, hospitals, and courtrooms look more like the numbers actually reflected in U.S. racial demographics and look less like Derek Chauvin.

Until there are more doctors who look like the racial breakdown of the nation, Black and Brown patients can never fully trust their primary care doctors, orthopedic surgeons, and psychiatrists who are White. While this reality may sound harsh, it is the reality for many of us who are dealing with trauma, grief, desensitization, dissociation, emotional numbness, or languishment resulting from racist experiences.

People of color cannot and will not stop protesting in the streets, being the one who always brings up race in the meeting, or disagreeing that the new changes are “not enough” until there is actual anti-racist institutional reform. More importantly, the efforts of people of color can be made more powerful working collectively with White allies.

But we need White allies who recognize their tendency to perceive “progress” in racial equality. We need White allies who recognize that despite the passage of the Civil Rights Act, the two-time election of a Black president, and the guilty verdict of Derek Chauvin, there is still so much work to do.
 

Dr. Cyrus is assistant professor in the department of psychiatry at Johns Hopkins University, Baltimore. She reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

On Tuesday, April 20, the country braced for the impact of the trial verdict in death of George Floyd. Despite the case having what many would consider an overwhelming amount of evidence pointing toward conviction, if we’re completely honest, the country – and particularly the African American community – had significant doubts that the jury would render a guilty verdict.

Nathan Howard/Stringer/Getty Images News

In the hour leading up to the announcement, people and images dominated my thoughts; Tamir Rice, Breonna Taylor, Eric Garner, Rashard Brooks, and most recently, Daunte Wright. With the deaths of these Black Americans and many others as historical context, I took a stoic stance and held my breath as the verdict was read. Former Minneapolis Police Officer Derek Chauvin was found guilty of second-degree murder, third-degree murder, and second-degree manslaughter.

As Mr. Chauvin was remanded to custody and led away in handcuffs, it was clear there were no “winners” in this verdict. Mr. Floyd is still dead, and violent encounters experienced by Black Americans continue at a vastly disproportionate rate. The result is far from true justice, but what we as a country do have is a moment of accountability – and perhaps an opportunity for true system-level reform.

The final report of the President’s Task Force on 21st Century Policing, released in May 2015, recommended major policy changes at the federal level and developed key pillars aimed at promoting effective crime reduction while building public trust. Based on this report, four key takeaways are relevant to any discussion of police reform. All are vitally important, but two stand out as particularly relevant in the aftermath of the verdict. One of the key recommendations was “embracing a guardian – rather than a warrior mindset” in an effort to build trust and legitimacy. Another was ensuring that “peace officer and standards training (POST) boards include mandatory Crisis Intervention Training.”

As health professionals, we know that the ultimate effectiveness of any intervention is based upon the amount of shared trust and collaboration in the patient-physician relationship. As a consultation-liaison psychiatrist, I’ve been trained to recognize that, when requested to consult on a case, I’m frequently not making a medical diagnosis or delivering an intervention; I’m helping the team and patient reestablish trust in each other. Communication skills and techniques help start a dialogue, but you will ultimately fall short of shared understanding without trust. The underpinning of trust could begin with a commitment to procedural justice. Procedural justice, as described in The Justice Collaboratory of Yale Law School, “speaks to the idea of fair processes and how the quality of their experiences strongly impacts people’s perception of fairness.” There are four central tenets of procedural justice:

• Whether they were treated with dignity and respect.
• Whether they were given voice.
• Whether the decision-maker was neutral and transparent.
• Whether the decision-maker conveyed trustworthy motives.

These four tenets have been researched and shown to improve the trust and confidence a community has in police, and lay the foundation for creating a standard set of shared interests and values.

As health professionals, there are many aspects of procedural justice that we can and should embrace, particularly as we come to our reckoning with the use of restraints in medical settings.

Building on the work of the Task Force on 21st Century Policing, the National Initiative for Building Community Trust and Justice, from January 2015 through December 2018, implemented a six-city intervention aimed at generating measurable improvements in officer behavior, public safety, and community trust in police. The National Initiative was organized around three principal ideas: procedural justice, implicit bias training, and reconciliation and candid conversations about law enforcement’s historic role in racial tensions.

In addition to the recommendations of the federal government and independent institutions, national-level health policy organizations have made clear statements regarding police brutality and the need for systemic reform to address police brutality and systemic racism. In 2018, the American Psychiatric Association released a position statement on Police Brutality and Black Males. This was then followed in 2020 with a joint statement from the National Medical Association and the APA condemning systemic racism and police violence against Black Americans. Other health policy associations, including the American Medical Association and the American Association of Medical Colleges, have made clear statements condemning systemic racism and police brutality.

In the aftermath of the verdict, we also saw something very different. In our partisan country, there appeared to be uniform common ground. Statements were made acknowledging the importance of this historic moment, from police unions, and both political parties, and various invested grassroots organizations. In short, we may have true agreement and motivation to take the next hard steps in police reform for this country. There will be policy discussions and new mandates for training, and certainly a push to ban the use of lethal techniques, such as choke holds. While helpful, these will ultimately fall short unless we hold ourselves accountable for a true culture change.

The challenge of implementing procedural justice shouldn’t be just a law enforcement challenge, and it shouldn’t fall on the shoulders of communities with high crime areas. In other words, no single racial group should own it. Ultimately, procedural justice will need to be embraced by all of us. The road is long, and change is slow, but I am optimistic.

On April 20, as I watched the verdict, my oldest daughter watched with me, and she asked, “What do you think, Dad?” I responded: “It’s accountability and an opportunity.” She nodded her head with resolve. She then grabbed her smartphone and jumped into social media and proclaimed in her very knowledgeable teenage voice, “See Dad, one voice is cool, but many voices in unison is better; time to get to work!” To Darnella Frazier, who captured the crime on video at age 17, and all in your generation who dare to hold us accountable, I salute you. I thank you for forcing us to look even when it was painful and not ignore the humanity of our fellow man. It is indeed time to get to work.

Dr. Norris is associate dean of student affairs and administration at George Washington University, Washington. He has no disclosures.

On Tuesday, April 20, the country braced for the impact of the trial verdict in death of George Floyd. Despite the case having what many would consider an overwhelming amount of evidence pointing toward conviction, if we’re completely honest, the country – and particularly the African American community – had significant doubts that the jury would render a guilty verdict.

Nathan Howard/Stringer/Getty Images News

In the hour leading up to the announcement, people and images dominated my thoughts; Tamir Rice, Breonna Taylor, Eric Garner, Rashard Brooks, and most recently, Daunte Wright. With the deaths of these Black Americans and many others as historical context, I took a stoic stance and held my breath as the verdict was read. Former Minneapolis Police Officer Derek Chauvin was found guilty of second-degree murder, third-degree murder, and second-degree manslaughter.

As Mr. Chauvin was remanded to custody and led away in handcuffs, it was clear there were no “winners” in this verdict. Mr. Floyd is still dead, and violent encounters experienced by Black Americans continue at a vastly disproportionate rate. The result is far from true justice, but what we as a country do have is a moment of accountability – and perhaps an opportunity for true system-level reform.

The final report of the President’s Task Force on 21st Century Policing, released in May 2015, recommended major policy changes at the federal level and developed key pillars aimed at promoting effective crime reduction while building public trust. Based on this report, four key takeaways are relevant to any discussion of police reform. All are vitally important, but two stand out as particularly relevant in the aftermath of the verdict. One of the key recommendations was “embracing a guardian – rather than a warrior mindset” in an effort to build trust and legitimacy. Another was ensuring that “peace officer and standards training (POST) boards include mandatory Crisis Intervention Training.”

As health professionals, we know that the ultimate effectiveness of any intervention is based upon the amount of shared trust and collaboration in the patient-physician relationship. As a consultation-liaison psychiatrist, I’ve been trained to recognize that, when requested to consult on a case, I’m frequently not making a medical diagnosis or delivering an intervention; I’m helping the team and patient reestablish trust in each other. Communication skills and techniques help start a dialogue, but you will ultimately fall short of shared understanding without trust. The underpinning of trust could begin with a commitment to procedural justice. Procedural justice, as described in The Justice Collaboratory of Yale Law School, “speaks to the idea of fair processes and how the quality of their experiences strongly impacts people’s perception of fairness.” There are four central tenets of procedural justice:

• Whether they were treated with dignity and respect.
• Whether they were given voice.
• Whether the decision-maker was neutral and transparent.
• Whether the decision-maker conveyed trustworthy motives.

These four tenets have been researched and shown to improve the trust and confidence a community has in police, and lay the foundation for creating a standard set of shared interests and values.

As health professionals, there are many aspects of procedural justice that we can and should embrace, particularly as we come to our reckoning with the use of restraints in medical settings.

Building on the work of the Task Force on 21st Century Policing, the National Initiative for Building Community Trust and Justice, from January 2015 through December 2018, implemented a six-city intervention aimed at generating measurable improvements in officer behavior, public safety, and community trust in police. The National Initiative was organized around three principal ideas: procedural justice, implicit bias training, and reconciliation and candid conversations about law enforcement’s historic role in racial tensions.

In addition to the recommendations of the federal government and independent institutions, national-level health policy organizations have made clear statements regarding police brutality and the need for systemic reform to address police brutality and systemic racism. In 2018, the American Psychiatric Association released a position statement on Police Brutality and Black Males. This was then followed in 2020 with a joint statement from the National Medical Association and the APA condemning systemic racism and police violence against Black Americans. Other health policy associations, including the American Medical Association and the American Association of Medical Colleges, have made clear statements condemning systemic racism and police brutality.

In the aftermath of the verdict, we also saw something very different. In our partisan country, there appeared to be uniform common ground. Statements were made acknowledging the importance of this historic moment, from police unions, and both political parties, and various invested grassroots organizations. In short, we may have true agreement and motivation to take the next hard steps in police reform for this country. There will be policy discussions and new mandates for training, and certainly a push to ban the use of lethal techniques, such as choke holds. While helpful, these will ultimately fall short unless we hold ourselves accountable for a true culture change.

The challenge of implementing procedural justice shouldn’t be just a law enforcement challenge, and it shouldn’t fall on the shoulders of communities with high crime areas. In other words, no single racial group should own it. Ultimately, procedural justice will need to be embraced by all of us. The road is long, and change is slow, but I am optimistic.

On April 20, as I watched the verdict, my oldest daughter watched with me, and she asked, “What do you think, Dad?” I responded: “It’s accountability and an opportunity.” She nodded her head with resolve. She then grabbed her smartphone and jumped into social media and proclaimed in her very knowledgeable teenage voice, “See Dad, one voice is cool, but many voices in unison is better; time to get to work!” To Darnella Frazier, who captured the crime on video at age 17, and all in your generation who dare to hold us accountable, I salute you. I thank you for forcing us to look even when it was painful and not ignore the humanity of our fellow man. It is indeed time to get to work.

Dr. Norris is associate dean of student affairs and administration at George Washington University, Washington. He has no disclosures.

On Tuesday, April 20, the country braced for the impact of the trial verdict in death of George Floyd. Despite the case having what many would consider an overwhelming amount of evidence pointing toward conviction, if we’re completely honest, the country – and particularly the African American community – had significant doubts that the jury would render a guilty verdict.

Nathan Howard/Stringer/Getty Images News

In the hour leading up to the announcement, people and images dominated my thoughts; Tamir Rice, Breonna Taylor, Eric Garner, Rashard Brooks, and most recently, Daunte Wright. With the deaths of these Black Americans and many others as historical context, I took a stoic stance and held my breath as the verdict was read. Former Minneapolis Police Officer Derek Chauvin was found guilty of second-degree murder, third-degree murder, and second-degree manslaughter.

As Mr. Chauvin was remanded to custody and led away in handcuffs, it was clear there were no “winners” in this verdict. Mr. Floyd is still dead, and violent encounters experienced by Black Americans continue at a vastly disproportionate rate. The result is far from true justice, but what we as a country do have is a moment of accountability – and perhaps an opportunity for true system-level reform.

The final report of the President’s Task Force on 21st Century Policing, released in May 2015, recommended major policy changes at the federal level and developed key pillars aimed at promoting effective crime reduction while building public trust. Based on this report, four key takeaways are relevant to any discussion of police reform. All are vitally important, but two stand out as particularly relevant in the aftermath of the verdict. One of the key recommendations was “embracing a guardian – rather than a warrior mindset” in an effort to build trust and legitimacy. Another was ensuring that “peace officer and standards training (POST) boards include mandatory Crisis Intervention Training.”

As health professionals, we know that the ultimate effectiveness of any intervention is based upon the amount of shared trust and collaboration in the patient-physician relationship. As a consultation-liaison psychiatrist, I’ve been trained to recognize that, when requested to consult on a case, I’m frequently not making a medical diagnosis or delivering an intervention; I’m helping the team and patient reestablish trust in each other. Communication skills and techniques help start a dialogue, but you will ultimately fall short of shared understanding without trust. The underpinning of trust could begin with a commitment to procedural justice. Procedural justice, as described in The Justice Collaboratory of Yale Law School, “speaks to the idea of fair processes and how the quality of their experiences strongly impacts people’s perception of fairness.” There are four central tenets of procedural justice:

• Whether they were treated with dignity and respect.
• Whether they were given voice.
• Whether the decision-maker was neutral and transparent.
• Whether the decision-maker conveyed trustworthy motives.

These four tenets have been researched and shown to improve the trust and confidence a community has in police, and lay the foundation for creating a standard set of shared interests and values.

As health professionals, there are many aspects of procedural justice that we can and should embrace, particularly as we come to our reckoning with the use of restraints in medical settings.

Building on the work of the Task Force on 21st Century Policing, the National Initiative for Building Community Trust and Justice, from January 2015 through December 2018, implemented a six-city intervention aimed at generating measurable improvements in officer behavior, public safety, and community trust in police. The National Initiative was organized around three principal ideas: procedural justice, implicit bias training, and reconciliation and candid conversations about law enforcement’s historic role in racial tensions.

In addition to the recommendations of the federal government and independent institutions, national-level health policy organizations have made clear statements regarding police brutality and the need for systemic reform to address police brutality and systemic racism. In 2018, the American Psychiatric Association released a position statement on Police Brutality and Black Males. This was then followed in 2020 with a joint statement from the National Medical Association and the APA condemning systemic racism and police violence against Black Americans. Other health policy associations, including the American Medical Association and the American Association of Medical Colleges, have made clear statements condemning systemic racism and police brutality.

In the aftermath of the verdict, we also saw something very different. In our partisan country, there appeared to be uniform common ground. Statements were made acknowledging the importance of this historic moment, from police unions, and both political parties, and various invested grassroots organizations. In short, we may have true agreement and motivation to take the next hard steps in police reform for this country. There will be policy discussions and new mandates for training, and certainly a push to ban the use of lethal techniques, such as choke holds. While helpful, these will ultimately fall short unless we hold ourselves accountable for a true culture change.

The challenge of implementing procedural justice shouldn’t be just a law enforcement challenge, and it shouldn’t fall on the shoulders of communities with high crime areas. In other words, no single racial group should own it. Ultimately, procedural justice will need to be embraced by all of us. The road is long, and change is slow, but I am optimistic.

On April 20, as I watched the verdict, my oldest daughter watched with me, and she asked, “What do you think, Dad?” I responded: “It’s accountability and an opportunity.” She nodded her head with resolve. She then grabbed her smartphone and jumped into social media and proclaimed in her very knowledgeable teenage voice, “See Dad, one voice is cool, but many voices in unison is better; time to get to work!” To Darnella Frazier, who captured the crime on video at age 17, and all in your generation who dare to hold us accountable, I salute you. I thank you for forcing us to look even when it was painful and not ignore the humanity of our fellow man. It is indeed time to get to work.

Dr. Norris is associate dean of student affairs and administration at George Washington University, Washington. He has no disclosures.

A study using data from Veterans Health Administration (VHA) electronic medical records shows a significant association between posttraumatic stress disorder (PTSD) among female veterans and an increased risk for incident ischemic heart disease (IHD).

The increased risk for IHD was highest among women younger than 40 with PTSD, and among racial and ethnic minorities.

“These women have been emerging as important targets for cardiovascular prevention, and our study suggests that PTSD may be an important psychosocial risk factor for IHD in these individuals,” wrote the researchers, led by Ramin Ebrahimi, MD, department of medicine, cardiology section, Veterans Affairs Greater Los Angeles Health Care System. “With the number of women veterans growing, it is critical to appreciate the health care needs of this relatively young and diverse patient population.”

The study results also have “important implications for earlier and more aggressive IHD risk assessment, monitoring and management in vulnerable women veterans,” they added. “Indeed, our findings support recent calls for cardiovascular risk screening in younger individuals and for the need to harness a broad range of clinicians who routinely treat younger women to maximize prevention efforts.”

The article was published online in JAMA Cardiology on March 17.
 

Increasing number of VHA users

“As an interventional cardiologist and the director of the cardiac catheterization laboratory, I noticed a significant number of the patients referred to the cath lab carried a diagnosis of posttraumatic stress disorder,” Dr. Ebrahimi said in an interview. “This intrigued me and started my journey into trying to understand how psychiatric disorders in general, and PTSD, may impact/interact with cardiovascular disorders,” he added.

The number of female veterans in the military has been increasing, and they now make up about 10% of the 20 million American veterans; that number is projected to exceed 2.2 million in the next 20 years, the authors wrote. Female veterans are also the fastest growing group of users of the VHA, they added.

IHD is the leading cause of death in women in the United States, despite the advancements in prevention and treatment. Although women are twice as likely to develop PTSD as are men, and it is even more likely in female veterans, much of the research has predominately been on male veterans, the authors wrote.

For this retrospective study, which used data from the VHA Corporate Data Warehouse, the authors examined a cohort of female veterans who were 18 years or older who had used the VHA health care system between Jan. 1, 2000, and Dec. 31, 2017.

Of the 828,997 female veterans, 151,030 had PTSD. Women excluded from the study were those who did not have any clinical encounters after their index visit, participants who had a diagnosis of IHD at or before the index visit, and those with incident IHD within 90 days of the index visit, allowing time between a PTSD diagnosis and IHD.

Propensity score matching on age at index visit, the number of previous visits, and the presence of traditional and female-specific cardiovascular risk factors, as well as mental and physical health conditions, was conducted to identify female veterans ever diagnosed with PTSD, who were matched in a 1:2 ratio to those never diagnosed with PTSD. In all, 132,923 women with PTSD and 265,846 women without PTSD were included, and data were analyzed for the period of Oct. 1, 2018, to Oct. 30, 2020.

IHD was defined as new-onset coronary artery disease, angina, or myocardial infarction–based ICD-9 and ICD-10 diagnostic codes. Age, race, and ethnicity were self-reported.

The analytic sample consisted of relatively young female veterans (mean [SD] age at baseline, 40.1 [12.2] years) of various races (White, 57.6%; Black, 29.8%) and ethnicities, the authors reported.

Of the 9,940 women who experienced incident IHD during follow-up, 5,559 did not have  PTSD (2.1% of the overall population examined) and 4,381 had PTSD (3.3%). PTSD was significantly associated with an increased risk for IHD. Over the median follow-up of 4.9 years, female veterans with PTSD had a 44% higher rate of developing incident IHD compared with the female veterans without PTSD (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.38-1.50).

In addition, those with PTSD who developed IHD were younger at diagnosis (mean [SD] age, 55.5 [9.7]) than were patients without PTSD (mean [SD] age, 57.8 [10.7]). Effect sizes were largest in the group younger than 40 years (HR, 1.72; 95% CI, 1.55-1.90) and decreased for older participants (HR for those ≥60 years, 1.24; 95% CI, 1.12-1.38)

The authors found a 49% to 66% increase in risk for IHD associated with PTSD in Black women (HR, 1.49; 95% CI, 1.38-1.62) and those identified as non-White and non-Black (HR, 1.66; 95%, 1.33-2.08).

Women of all ethnic groups with PTSD were at higher risk of developing IHD, but this was especially true for Hispanic/Latina women (HR, 1.50; 95% CI 1.22-1.84), they noted.

The authors reported some limitations to their findings. The analytic sample could result in a lower ascertainment of certain conditions, such as psychiatric disorders, they wrote. Substance disorders were low in this study, possibly because of the younger age of female veterans in the sample. Because this study used VHA electronic medical records data, medical care outside of the VHA that was not paid for by the VHA could not be considered.

In addition, although this study used a large sample of female veterans, the findings cannot be generalized to female veterans outside of the VHA system, nonveteran women, or men, the researchers wrote.


 

A call to action

In an accompanying comment, Beth E. Cohen, MD, of the University of California, San Francisco, and the San Francisco Veterans Affairs Health Care System, points out that the physical implications for psychosocial conditions, including depression and PTSD, have been recognized for quite some time. For example, results of the INTERHEART case-control study of 30,000 people showed stress, depression, and stressful life events accounted for one-third the population-attributable risk for myocardial infarction.

As was also noted by Dr. Ebrahimi and colleagues, much of the current research has been on male veterans, yet types of trauma differ among genders; women experience higher rates of military sexual trauma but lower rates of combat trauma, Dr. Cohen wrote. The PTSD symptoms, trajectory, and biological effects can differ for women and men, as can the pathogenesis, presentation, and outcomes of cardiovascular disease (CVD).

These findings, she said, “are an important extension of the prior literature and represent the largest study in female veterans to date. Although methods differ across studies, the magnitude of risk associated with PTSD was consistent with that found in prior studies of male veterans and nonveteran samples.”

The assessment of age-specific risk is also a strength of the study, “and has implications for clinical practice, because PTSD-associated risk was greatest in a younger group in whom CVD may be overlooked.”

Dr. Cohen addressed the limitations outlined by the authors, including ascertainment bias, severity of PTSD symptoms, and their chronicity, but added that “even in the context of these limitations, this study illustrates the importance of PTSD to the health of women veterans and the additional work needed to reduce their CVD risk.”

Clinical questions remain, she added. Screens for PTSD are widely used in the VHA, yet no studies have examined whether screening or early detection decrease CVD risk. In addition, no evidence suggests that screening for or treatment of PTSD improves cardiovascular outcomes.

“Given the challenges of answering these questions in observational studies, it will be important to incorporate measures of CVD risk and outcomes in trials of behavioral and medical therapies for patients with PTSD,” she wrote.

She added that collaborations among multidisciplinary patient care teams will be important. “The findings of this study represent a call to action for this important work to understand the cardiovascular effects of PTSD and improve the health and well-being of women veterans,” Dr. Cohen concluded.

This research was supported by Investigator-Initiated Research Award from the Department of Defense U.S. Army Medical Research and Material Command Congressionally Directed Medical Research Programs (Dr. Ebrahimi) and in part by grants from the VA Informatics and Computing Infrastructure and the Offices of Research and Development at the Northport, Durham, and Greater Los Angeles Veterans Affairs medical centers. Dr. Ebrahimi reported receiving grants from the Department of Defense during the conduct of the study. Disclosures for other authors are available in the paper. Dr. Cohen reports no disclosures.
 

A version of this article first appeared on Medscape.com.

A study using data from Veterans Health Administration (VHA) electronic medical records shows a significant association between posttraumatic stress disorder (PTSD) among female veterans and an increased risk for incident ischemic heart disease (IHD).

The increased risk for IHD was highest among women younger than 40 with PTSD, and among racial and ethnic minorities.

“These women have been emerging as important targets for cardiovascular prevention, and our study suggests that PTSD may be an important psychosocial risk factor for IHD in these individuals,” wrote the researchers, led by Ramin Ebrahimi, MD, department of medicine, cardiology section, Veterans Affairs Greater Los Angeles Health Care System. “With the number of women veterans growing, it is critical to appreciate the health care needs of this relatively young and diverse patient population.”

The study results also have “important implications for earlier and more aggressive IHD risk assessment, monitoring and management in vulnerable women veterans,” they added. “Indeed, our findings support recent calls for cardiovascular risk screening in younger individuals and for the need to harness a broad range of clinicians who routinely treat younger women to maximize prevention efforts.”

The article was published online in JAMA Cardiology on March 17.
 

Increasing number of VHA users

“As an interventional cardiologist and the director of the cardiac catheterization laboratory, I noticed a significant number of the patients referred to the cath lab carried a diagnosis of posttraumatic stress disorder,” Dr. Ebrahimi said in an interview. “This intrigued me and started my journey into trying to understand how psychiatric disorders in general, and PTSD, may impact/interact with cardiovascular disorders,” he added.

The number of female veterans in the military has been increasing, and they now make up about 10% of the 20 million American veterans; that number is projected to exceed 2.2 million in the next 20 years, the authors wrote. Female veterans are also the fastest growing group of users of the VHA, they added.

IHD is the leading cause of death in women in the United States, despite the advancements in prevention and treatment. Although women are twice as likely to develop PTSD as are men, and it is even more likely in female veterans, much of the research has predominately been on male veterans, the authors wrote.

For this retrospective study, which used data from the VHA Corporate Data Warehouse, the authors examined a cohort of female veterans who were 18 years or older who had used the VHA health care system between Jan. 1, 2000, and Dec. 31, 2017.

Of the 828,997 female veterans, 151,030 had PTSD. Women excluded from the study were those who did not have any clinical encounters after their index visit, participants who had a diagnosis of IHD at or before the index visit, and those with incident IHD within 90 days of the index visit, allowing time between a PTSD diagnosis and IHD.

Propensity score matching on age at index visit, the number of previous visits, and the presence of traditional and female-specific cardiovascular risk factors, as well as mental and physical health conditions, was conducted to identify female veterans ever diagnosed with PTSD, who were matched in a 1:2 ratio to those never diagnosed with PTSD. In all, 132,923 women with PTSD and 265,846 women without PTSD were included, and data were analyzed for the period of Oct. 1, 2018, to Oct. 30, 2020.

IHD was defined as new-onset coronary artery disease, angina, or myocardial infarction–based ICD-9 and ICD-10 diagnostic codes. Age, race, and ethnicity were self-reported.

The analytic sample consisted of relatively young female veterans (mean [SD] age at baseline, 40.1 [12.2] years) of various races (White, 57.6%; Black, 29.8%) and ethnicities, the authors reported.

Of the 9,940 women who experienced incident IHD during follow-up, 5,559 did not have  PTSD (2.1% of the overall population examined) and 4,381 had PTSD (3.3%). PTSD was significantly associated with an increased risk for IHD. Over the median follow-up of 4.9 years, female veterans with PTSD had a 44% higher rate of developing incident IHD compared with the female veterans without PTSD (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.38-1.50).

In addition, those with PTSD who developed IHD were younger at diagnosis (mean [SD] age, 55.5 [9.7]) than were patients without PTSD (mean [SD] age, 57.8 [10.7]). Effect sizes were largest in the group younger than 40 years (HR, 1.72; 95% CI, 1.55-1.90) and decreased for older participants (HR for those ≥60 years, 1.24; 95% CI, 1.12-1.38)

The authors found a 49% to 66% increase in risk for IHD associated with PTSD in Black women (HR, 1.49; 95% CI, 1.38-1.62) and those identified as non-White and non-Black (HR, 1.66; 95%, 1.33-2.08).

Women of all ethnic groups with PTSD were at higher risk of developing IHD, but this was especially true for Hispanic/Latina women (HR, 1.50; 95% CI 1.22-1.84), they noted.

The authors reported some limitations to their findings. The analytic sample could result in a lower ascertainment of certain conditions, such as psychiatric disorders, they wrote. Substance disorders were low in this study, possibly because of the younger age of female veterans in the sample. Because this study used VHA electronic medical records data, medical care outside of the VHA that was not paid for by the VHA could not be considered.

In addition, although this study used a large sample of female veterans, the findings cannot be generalized to female veterans outside of the VHA system, nonveteran women, or men, the researchers wrote.


 

A call to action

In an accompanying comment, Beth E. Cohen, MD, of the University of California, San Francisco, and the San Francisco Veterans Affairs Health Care System, points out that the physical implications for psychosocial conditions, including depression and PTSD, have been recognized for quite some time. For example, results of the INTERHEART case-control study of 30,000 people showed stress, depression, and stressful life events accounted for one-third the population-attributable risk for myocardial infarction.

As was also noted by Dr. Ebrahimi and colleagues, much of the current research has been on male veterans, yet types of trauma differ among genders; women experience higher rates of military sexual trauma but lower rates of combat trauma, Dr. Cohen wrote. The PTSD symptoms, trajectory, and biological effects can differ for women and men, as can the pathogenesis, presentation, and outcomes of cardiovascular disease (CVD).

These findings, she said, “are an important extension of the prior literature and represent the largest study in female veterans to date. Although methods differ across studies, the magnitude of risk associated with PTSD was consistent with that found in prior studies of male veterans and nonveteran samples.”

The assessment of age-specific risk is also a strength of the study, “and has implications for clinical practice, because PTSD-associated risk was greatest in a younger group in whom CVD may be overlooked.”

Dr. Cohen addressed the limitations outlined by the authors, including ascertainment bias, severity of PTSD symptoms, and their chronicity, but added that “even in the context of these limitations, this study illustrates the importance of PTSD to the health of women veterans and the additional work needed to reduce their CVD risk.”

Clinical questions remain, she added. Screens for PTSD are widely used in the VHA, yet no studies have examined whether screening or early detection decrease CVD risk. In addition, no evidence suggests that screening for or treatment of PTSD improves cardiovascular outcomes.

“Given the challenges of answering these questions in observational studies, it will be important to incorporate measures of CVD risk and outcomes in trials of behavioral and medical therapies for patients with PTSD,” she wrote.

She added that collaborations among multidisciplinary patient care teams will be important. “The findings of this study represent a call to action for this important work to understand the cardiovascular effects of PTSD and improve the health and well-being of women veterans,” Dr. Cohen concluded.

This research was supported by Investigator-Initiated Research Award from the Department of Defense U.S. Army Medical Research and Material Command Congressionally Directed Medical Research Programs (Dr. Ebrahimi) and in part by grants from the VA Informatics and Computing Infrastructure and the Offices of Research and Development at the Northport, Durham, and Greater Los Angeles Veterans Affairs medical centers. Dr. Ebrahimi reported receiving grants from the Department of Defense during the conduct of the study. Disclosures for other authors are available in the paper. Dr. Cohen reports no disclosures.
 

A version of this article first appeared on Medscape.com.

A study using data from Veterans Health Administration (VHA) electronic medical records shows a significant association between posttraumatic stress disorder (PTSD) among female veterans and an increased risk for incident ischemic heart disease (IHD).

The increased risk for IHD was highest among women younger than 40 with PTSD, and among racial and ethnic minorities.

“These women have been emerging as important targets for cardiovascular prevention, and our study suggests that PTSD may be an important psychosocial risk factor for IHD in these individuals,” wrote the researchers, led by Ramin Ebrahimi, MD, department of medicine, cardiology section, Veterans Affairs Greater Los Angeles Health Care System. “With the number of women veterans growing, it is critical to appreciate the health care needs of this relatively young and diverse patient population.”

The study results also have “important implications for earlier and more aggressive IHD risk assessment, monitoring and management in vulnerable women veterans,” they added. “Indeed, our findings support recent calls for cardiovascular risk screening in younger individuals and for the need to harness a broad range of clinicians who routinely treat younger women to maximize prevention efforts.”

The article was published online in JAMA Cardiology on March 17.
 

Increasing number of VHA users

“As an interventional cardiologist and the director of the cardiac catheterization laboratory, I noticed a significant number of the patients referred to the cath lab carried a diagnosis of posttraumatic stress disorder,” Dr. Ebrahimi said in an interview. “This intrigued me and started my journey into trying to understand how psychiatric disorders in general, and PTSD, may impact/interact with cardiovascular disorders,” he added.

The number of female veterans in the military has been increasing, and they now make up about 10% of the 20 million American veterans; that number is projected to exceed 2.2 million in the next 20 years, the authors wrote. Female veterans are also the fastest growing group of users of the VHA, they added.

IHD is the leading cause of death in women in the United States, despite the advancements in prevention and treatment. Although women are twice as likely to develop PTSD as are men, and it is even more likely in female veterans, much of the research has predominately been on male veterans, the authors wrote.

For this retrospective study, which used data from the VHA Corporate Data Warehouse, the authors examined a cohort of female veterans who were 18 years or older who had used the VHA health care system between Jan. 1, 2000, and Dec. 31, 2017.

Of the 828,997 female veterans, 151,030 had PTSD. Women excluded from the study were those who did not have any clinical encounters after their index visit, participants who had a diagnosis of IHD at or before the index visit, and those with incident IHD within 90 days of the index visit, allowing time between a PTSD diagnosis and IHD.

Propensity score matching on age at index visit, the number of previous visits, and the presence of traditional and female-specific cardiovascular risk factors, as well as mental and physical health conditions, was conducted to identify female veterans ever diagnosed with PTSD, who were matched in a 1:2 ratio to those never diagnosed with PTSD. In all, 132,923 women with PTSD and 265,846 women without PTSD were included, and data were analyzed for the period of Oct. 1, 2018, to Oct. 30, 2020.

IHD was defined as new-onset coronary artery disease, angina, or myocardial infarction–based ICD-9 and ICD-10 diagnostic codes. Age, race, and ethnicity were self-reported.

The analytic sample consisted of relatively young female veterans (mean [SD] age at baseline, 40.1 [12.2] years) of various races (White, 57.6%; Black, 29.8%) and ethnicities, the authors reported.

Of the 9,940 women who experienced incident IHD during follow-up, 5,559 did not have  PTSD (2.1% of the overall population examined) and 4,381 had PTSD (3.3%). PTSD was significantly associated with an increased risk for IHD. Over the median follow-up of 4.9 years, female veterans with PTSD had a 44% higher rate of developing incident IHD compared with the female veterans without PTSD (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.38-1.50).

In addition, those with PTSD who developed IHD were younger at diagnosis (mean [SD] age, 55.5 [9.7]) than were patients without PTSD (mean [SD] age, 57.8 [10.7]). Effect sizes were largest in the group younger than 40 years (HR, 1.72; 95% CI, 1.55-1.90) and decreased for older participants (HR for those ≥60 years, 1.24; 95% CI, 1.12-1.38)

The authors found a 49% to 66% increase in risk for IHD associated with PTSD in Black women (HR, 1.49; 95% CI, 1.38-1.62) and those identified as non-White and non-Black (HR, 1.66; 95%, 1.33-2.08).

Women of all ethnic groups with PTSD were at higher risk of developing IHD, but this was especially true for Hispanic/Latina women (HR, 1.50; 95% CI 1.22-1.84), they noted.

The authors reported some limitations to their findings. The analytic sample could result in a lower ascertainment of certain conditions, such as psychiatric disorders, they wrote. Substance disorders were low in this study, possibly because of the younger age of female veterans in the sample. Because this study used VHA electronic medical records data, medical care outside of the VHA that was not paid for by the VHA could not be considered.

In addition, although this study used a large sample of female veterans, the findings cannot be generalized to female veterans outside of the VHA system, nonveteran women, or men, the researchers wrote.


 

A call to action

In an accompanying comment, Beth E. Cohen, MD, of the University of California, San Francisco, and the San Francisco Veterans Affairs Health Care System, points out that the physical implications for psychosocial conditions, including depression and PTSD, have been recognized for quite some time. For example, results of the INTERHEART case-control study of 30,000 people showed stress, depression, and stressful life events accounted for one-third the population-attributable risk for myocardial infarction.

As was also noted by Dr. Ebrahimi and colleagues, much of the current research has been on male veterans, yet types of trauma differ among genders; women experience higher rates of military sexual trauma but lower rates of combat trauma, Dr. Cohen wrote. The PTSD symptoms, trajectory, and biological effects can differ for women and men, as can the pathogenesis, presentation, and outcomes of cardiovascular disease (CVD).

These findings, she said, “are an important extension of the prior literature and represent the largest study in female veterans to date. Although methods differ across studies, the magnitude of risk associated with PTSD was consistent with that found in prior studies of male veterans and nonveteran samples.”

The assessment of age-specific risk is also a strength of the study, “and has implications for clinical practice, because PTSD-associated risk was greatest in a younger group in whom CVD may be overlooked.”

Dr. Cohen addressed the limitations outlined by the authors, including ascertainment bias, severity of PTSD symptoms, and their chronicity, but added that “even in the context of these limitations, this study illustrates the importance of PTSD to the health of women veterans and the additional work needed to reduce their CVD risk.”

Clinical questions remain, she added. Screens for PTSD are widely used in the VHA, yet no studies have examined whether screening or early detection decrease CVD risk. In addition, no evidence suggests that screening for or treatment of PTSD improves cardiovascular outcomes.

“Given the challenges of answering these questions in observational studies, it will be important to incorporate measures of CVD risk and outcomes in trials of behavioral and medical therapies for patients with PTSD,” she wrote.

She added that collaborations among multidisciplinary patient care teams will be important. “The findings of this study represent a call to action for this important work to understand the cardiovascular effects of PTSD and improve the health and well-being of women veterans,” Dr. Cohen concluded.

This research was supported by Investigator-Initiated Research Award from the Department of Defense U.S. Army Medical Research and Material Command Congressionally Directed Medical Research Programs (Dr. Ebrahimi) and in part by grants from the VA Informatics and Computing Infrastructure and the Offices of Research and Development at the Northport, Durham, and Greater Los Angeles Veterans Affairs medical centers. Dr. Ebrahimi reported receiving grants from the Department of Defense during the conduct of the study. Disclosures for other authors are available in the paper. Dr. Cohen reports no disclosures.
 

A version of this article first appeared on Medscape.com.

Adding 3,4-methylenedioxymethamphetamine (MDMA) to integrative psychotherapy may significantly improve symptoms and well-being for patients with severe posttraumatic stress disorder, including those with the dissociative subtype, new research suggests.

MAPP1 is the first phase 3 randomized controlled trial of MDMA-assisted therapy in this population. Participants who received the active treatment showed greater improvement in PTSD symptoms, mood, and empathy in comparison with participants who received placebo.

MDMA was “extremely effective, particularly for a subpopulation that ordinarily does not respond well to conventional treatment,” study coinvestigator Bessel van der Kolk, MD, professor of psychiatry at Boston University School of Medicine, told delegates attending the virtual European Psychiatric Association (EPA) 2021 Congress.
 

Growing interest

In recent years, there has been a great deal of interest in the potential of MDMA for the treatment of PTSD, particularly because failure rates with most available evidence-based treatments have been relatively high.

As previously reported by this news organization, in 2017, the U.S. Food and Drug Administration approved the trial design of Dr. van der Kolk’s and colleagues’ MAPP1 study after granting MDMA breakthrough designation.

The MAPP1 investigators assessed 90 patients with PTSD (mean age, 41 years; 77% White; 66% women) from 50 sites. For the majority of patients (84%), trauma history was developmental. “In other words, trauma [occurred] very early in life, usually at the hands of their own caregivers,” Dr. van der Kolk noted.

In addition, 18% of the patients were veterans, and 12% had combat exposure. The average duration of PTSD before enrollment was 18 years. All patients underwent screening and three preparatory psychotherapy sessions at enrollment.

Participants were randomly assigned to receive MDMA 80 mg or 120 mg (n = 46) or placebo (n = 44) followed by three integrative psychotherapy sessions lasting a total of 8 hours. A supplemental dose of 40 or 60 mg of MDMA could be administered from 1.5 to 2 hours after the first dose.

The patients stayed in the laboratory on the evening of the treatment session and attended a debriefing the next morning. The session was repeated a month later and again a month after that. In between, patients had telephone contact with the raters, who were blinded to the treatment received.

Follow-up assessments were conducted 2 months after the third treatment session and again at 12 months. The primary outcome measure was change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) score from baseline.
 

‘Dramatic improvement’

Results showed that both the MDMA and placebo groups experienced a statistically significant improvement in PTSD symptoms, “but MDMA had a dramatically significant improvement, with an effect size of over 0.9,” Dr. van der Kolk said.

The MDMA group also reported enhanced mood and well-being, increased responsiveness to emotional and sensory stimuli, a greater sense of closeness to other people, and a greater feeling of empathy.

Patients also reported having heightened openness, “and clearly the issue of empathy for themselves and others was a very large part of the process,” said Dr. van der Kolk.

“But for me, the most interesting part of the study is that the Adverse Childhood Experiences scale had no effect,” he noted. In other words, “the amount of childhood adverse experiences did not predict outcomes, which was very surprising because usually those patients are very treatment resistant.”

Dr. van der Kolk added that the dissociative subtype of PTSD was first described in the DSM-5 and that patients are “notoriously unresponsive to most unconventional treatments.”

In the current study, 13 patients met the criteria for the subtype, and investigators found they “did better than people with classical PTSD,” Dr. van der Kolk said. He added that this is a “very, very important finding.”
 

Carefully controlled

Overall, 82% of patients reported a significant improvement by the end of the study; 56% reported that they no longer had PTSD.

In addition, 67% of patients no longer met diagnostic criteria for PTSD. These included patients who had crossed over to active treatment from the placebo group.

Eleven patients (12%) experienced relapse by 12 months; in nine of the cases, this was due to the presence of additional stressors.

There were “very few adverse side effects” during the study, Dr. van der Kolk noted. In addition, “there were really no serious mental side effects,” despite the patients’ “opening up so much very painful material,” he added.

The most common adverse events among the MDMA group were muscle tightness (63%), decreased appetite (52%), nausea (30%), hyperhidrosis (20%), and feeling cold (20%). These effects were “quite small [and] the sort of side effects you would expect in response to an amphetamine substance like MDMA,” said Dr. van der Kolk.

“An important reason why we think the side effect profile is so good is because the study was extremely carefully done, very carefully controlled,” he added. “There was a great deal of support, [and] we paid an enormous amount of attention to creating a very safe context in which this drug was being used.”

However, he expressed concern that “as people see the very good results, they may skimp a little bit on the creation of the context and not have as careful a psychotherapy protocol as we had here.”
 

‘On the right track’

Commenting on the findings for this news organization, David Nutt, MD, PhD, Edmond J. Safra Professor of Neuropsychopharmacology, Imperial College London, said the results are proof that the investigators’ “earlier smaller trials of MDMA were on the right track.”

“This larger and multicenter trial shows that MDMA therapy can be broadened into newer research groups, which augurs well for the much larger rollout that will be required once it gets a license,” said Dr. Nutt, who was not involved with the research.

He added, “the prior evidence of the safety of MDMA has [now] been confirmed.”

The study represents an “important step in the path to the clinical use of MDMA for PTSD,” Dr. Nutt said.

The study was sponsored by the Multidisciplinary Association for Psychedelic Studies. The investigators and Dr. Nutt have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adding 3,4-methylenedioxymethamphetamine (MDMA) to integrative psychotherapy may significantly improve symptoms and well-being for patients with severe posttraumatic stress disorder, including those with the dissociative subtype, new research suggests.

MAPP1 is the first phase 3 randomized controlled trial of MDMA-assisted therapy in this population. Participants who received the active treatment showed greater improvement in PTSD symptoms, mood, and empathy in comparison with participants who received placebo.

MDMA was “extremely effective, particularly for a subpopulation that ordinarily does not respond well to conventional treatment,” study coinvestigator Bessel van der Kolk, MD, professor of psychiatry at Boston University School of Medicine, told delegates attending the virtual European Psychiatric Association (EPA) 2021 Congress.
 

Growing interest

In recent years, there has been a great deal of interest in the potential of MDMA for the treatment of PTSD, particularly because failure rates with most available evidence-based treatments have been relatively high.

As previously reported by this news organization, in 2017, the U.S. Food and Drug Administration approved the trial design of Dr. van der Kolk’s and colleagues’ MAPP1 study after granting MDMA breakthrough designation.

The MAPP1 investigators assessed 90 patients with PTSD (mean age, 41 years; 77% White; 66% women) from 50 sites. For the majority of patients (84%), trauma history was developmental. “In other words, trauma [occurred] very early in life, usually at the hands of their own caregivers,” Dr. van der Kolk noted.

In addition, 18% of the patients were veterans, and 12% had combat exposure. The average duration of PTSD before enrollment was 18 years. All patients underwent screening and three preparatory psychotherapy sessions at enrollment.

Participants were randomly assigned to receive MDMA 80 mg or 120 mg (n = 46) or placebo (n = 44) followed by three integrative psychotherapy sessions lasting a total of 8 hours. A supplemental dose of 40 or 60 mg of MDMA could be administered from 1.5 to 2 hours after the first dose.

The patients stayed in the laboratory on the evening of the treatment session and attended a debriefing the next morning. The session was repeated a month later and again a month after that. In between, patients had telephone contact with the raters, who were blinded to the treatment received.

Follow-up assessments were conducted 2 months after the third treatment session and again at 12 months. The primary outcome measure was change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) score from baseline.
 

‘Dramatic improvement’

Results showed that both the MDMA and placebo groups experienced a statistically significant improvement in PTSD symptoms, “but MDMA had a dramatically significant improvement, with an effect size of over 0.9,” Dr. van der Kolk said.

The MDMA group also reported enhanced mood and well-being, increased responsiveness to emotional and sensory stimuli, a greater sense of closeness to other people, and a greater feeling of empathy.

Patients also reported having heightened openness, “and clearly the issue of empathy for themselves and others was a very large part of the process,” said Dr. van der Kolk.

“But for me, the most interesting part of the study is that the Adverse Childhood Experiences scale had no effect,” he noted. In other words, “the amount of childhood adverse experiences did not predict outcomes, which was very surprising because usually those patients are very treatment resistant.”

Dr. van der Kolk added that the dissociative subtype of PTSD was first described in the DSM-5 and that patients are “notoriously unresponsive to most unconventional treatments.”

In the current study, 13 patients met the criteria for the subtype, and investigators found they “did better than people with classical PTSD,” Dr. van der Kolk said. He added that this is a “very, very important finding.”
 

Carefully controlled

Overall, 82% of patients reported a significant improvement by the end of the study; 56% reported that they no longer had PTSD.

In addition, 67% of patients no longer met diagnostic criteria for PTSD. These included patients who had crossed over to active treatment from the placebo group.

Eleven patients (12%) experienced relapse by 12 months; in nine of the cases, this was due to the presence of additional stressors.

There were “very few adverse side effects” during the study, Dr. van der Kolk noted. In addition, “there were really no serious mental side effects,” despite the patients’ “opening up so much very painful material,” he added.

The most common adverse events among the MDMA group were muscle tightness (63%), decreased appetite (52%), nausea (30%), hyperhidrosis (20%), and feeling cold (20%). These effects were “quite small [and] the sort of side effects you would expect in response to an amphetamine substance like MDMA,” said Dr. van der Kolk.

“An important reason why we think the side effect profile is so good is because the study was extremely carefully done, very carefully controlled,” he added. “There was a great deal of support, [and] we paid an enormous amount of attention to creating a very safe context in which this drug was being used.”

However, he expressed concern that “as people see the very good results, they may skimp a little bit on the creation of the context and not have as careful a psychotherapy protocol as we had here.”
 

‘On the right track’

Commenting on the findings for this news organization, David Nutt, MD, PhD, Edmond J. Safra Professor of Neuropsychopharmacology, Imperial College London, said the results are proof that the investigators’ “earlier smaller trials of MDMA were on the right track.”

“This larger and multicenter trial shows that MDMA therapy can be broadened into newer research groups, which augurs well for the much larger rollout that will be required once it gets a license,” said Dr. Nutt, who was not involved with the research.

He added, “the prior evidence of the safety of MDMA has [now] been confirmed.”

The study represents an “important step in the path to the clinical use of MDMA for PTSD,” Dr. Nutt said.

The study was sponsored by the Multidisciplinary Association for Psychedelic Studies. The investigators and Dr. Nutt have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adding 3,4-methylenedioxymethamphetamine (MDMA) to integrative psychotherapy may significantly improve symptoms and well-being for patients with severe posttraumatic stress disorder, including those with the dissociative subtype, new research suggests.

MAPP1 is the first phase 3 randomized controlled trial of MDMA-assisted therapy in this population. Participants who received the active treatment showed greater improvement in PTSD symptoms, mood, and empathy in comparison with participants who received placebo.

MDMA was “extremely effective, particularly for a subpopulation that ordinarily does not respond well to conventional treatment,” study coinvestigator Bessel van der Kolk, MD, professor of psychiatry at Boston University School of Medicine, told delegates attending the virtual European Psychiatric Association (EPA) 2021 Congress.
 

Growing interest

In recent years, there has been a great deal of interest in the potential of MDMA for the treatment of PTSD, particularly because failure rates with most available evidence-based treatments have been relatively high.

As previously reported by this news organization, in 2017, the U.S. Food and Drug Administration approved the trial design of Dr. van der Kolk’s and colleagues’ MAPP1 study after granting MDMA breakthrough designation.

The MAPP1 investigators assessed 90 patients with PTSD (mean age, 41 years; 77% White; 66% women) from 50 sites. For the majority of patients (84%), trauma history was developmental. “In other words, trauma [occurred] very early in life, usually at the hands of their own caregivers,” Dr. van der Kolk noted.

In addition, 18% of the patients were veterans, and 12% had combat exposure. The average duration of PTSD before enrollment was 18 years. All patients underwent screening and three preparatory psychotherapy sessions at enrollment.

Participants were randomly assigned to receive MDMA 80 mg or 120 mg (n = 46) or placebo (n = 44) followed by three integrative psychotherapy sessions lasting a total of 8 hours. A supplemental dose of 40 or 60 mg of MDMA could be administered from 1.5 to 2 hours after the first dose.

The patients stayed in the laboratory on the evening of the treatment session and attended a debriefing the next morning. The session was repeated a month later and again a month after that. In between, patients had telephone contact with the raters, who were blinded to the treatment received.

Follow-up assessments were conducted 2 months after the third treatment session and again at 12 months. The primary outcome measure was change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) score from baseline.
 

‘Dramatic improvement’

Results showed that both the MDMA and placebo groups experienced a statistically significant improvement in PTSD symptoms, “but MDMA had a dramatically significant improvement, with an effect size of over 0.9,” Dr. van der Kolk said.

The MDMA group also reported enhanced mood and well-being, increased responsiveness to emotional and sensory stimuli, a greater sense of closeness to other people, and a greater feeling of empathy.

Patients also reported having heightened openness, “and clearly the issue of empathy for themselves and others was a very large part of the process,” said Dr. van der Kolk.

“But for me, the most interesting part of the study is that the Adverse Childhood Experiences scale had no effect,” he noted. In other words, “the amount of childhood adverse experiences did not predict outcomes, which was very surprising because usually those patients are very treatment resistant.”

Dr. van der Kolk added that the dissociative subtype of PTSD was first described in the DSM-5 and that patients are “notoriously unresponsive to most unconventional treatments.”

In the current study, 13 patients met the criteria for the subtype, and investigators found they “did better than people with classical PTSD,” Dr. van der Kolk said. He added that this is a “very, very important finding.”
 

Carefully controlled

Overall, 82% of patients reported a significant improvement by the end of the study; 56% reported that they no longer had PTSD.

In addition, 67% of patients no longer met diagnostic criteria for PTSD. These included patients who had crossed over to active treatment from the placebo group.

Eleven patients (12%) experienced relapse by 12 months; in nine of the cases, this was due to the presence of additional stressors.

There were “very few adverse side effects” during the study, Dr. van der Kolk noted. In addition, “there were really no serious mental side effects,” despite the patients’ “opening up so much very painful material,” he added.

The most common adverse events among the MDMA group were muscle tightness (63%), decreased appetite (52%), nausea (30%), hyperhidrosis (20%), and feeling cold (20%). These effects were “quite small [and] the sort of side effects you would expect in response to an amphetamine substance like MDMA,” said Dr. van der Kolk.

“An important reason why we think the side effect profile is so good is because the study was extremely carefully done, very carefully controlled,” he added. “There was a great deal of support, [and] we paid an enormous amount of attention to creating a very safe context in which this drug was being used.”

However, he expressed concern that “as people see the very good results, they may skimp a little bit on the creation of the context and not have as careful a psychotherapy protocol as we had here.”
 

‘On the right track’

Commenting on the findings for this news organization, David Nutt, MD, PhD, Edmond J. Safra Professor of Neuropsychopharmacology, Imperial College London, said the results are proof that the investigators’ “earlier smaller trials of MDMA were on the right track.”

“This larger and multicenter trial shows that MDMA therapy can be broadened into newer research groups, which augurs well for the much larger rollout that will be required once it gets a license,” said Dr. Nutt, who was not involved with the research.

He added, “the prior evidence of the safety of MDMA has [now] been confirmed.”

The study represents an “important step in the path to the clinical use of MDMA for PTSD,” Dr. Nutt said.

The study was sponsored by the Multidisciplinary Association for Psychedelic Studies. The investigators and Dr. Nutt have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A 57-year-old woman with a history of traumatic brain injury, posttraumatic stress disorder, depression, migraines, hypothyroidism, and a hiatal hernia repair presented to the emergency department with a 1-day history of nausea, vomiting, and diffuse abdominal pain. She reported that her symptoms were relieved by hot showers. She also reported having similar symptoms and a previous gastric-emptying study that showed a slow-emptying stomach. Her history also consisted of frequent cannabis use for mood and appetite stimulation along with eliminating meat and fish from her diet, an increase in consumption of simple carbohydrates in the past year, and no alcohol use. Her medications included topiramate 100 mg and clonidine 0.3 mg nightly for migraines; levothyroxine 200 mcg daily for hypothyroidism; tizanidine 4 mg twice a day for muscle spasm; famotidine 40 mg twice a day as needed for gastric reflux; and bupropion 50 mg daily, citalopram 20 mg daily, and lamotrigine 25 mg nightly for mood.

The patient’s physical examination was notable for bradycardia (43 beats/min) and epigastric tenderness. Admission laboratory results were notable for an elevated lactic acid level of 4.8 (normal range, 0.50-2.20) mmol/L and a leukocytosis count of 10.8×10⁹ cells/L. Serum alcohol level and blood cultures were negative. Liver function test, hemoglobin A_1c, and lipase test were unremarkable. Her electrocardiogram showed an unchanged right bundle branch block. Chest X-ray, computed tomography (CT) of her abdomen/pelvis and echocardiogram were unremarkable.

What is your diagnosis? 

How would you treat this patient? 

This patient was diagnosed with gastrointestinal beriberi. Because of her dietary changes, lactic acidosis, and bradycardia, thiamine deficiency was suspected after ruling out other possibilities on the differential diagnosis (Table). The patient’s symptoms resolved after administration of high-dose IV thiamine 500 mg 3 times daily for 4 days. Her white blood cell count and lactic acid level normalized. Unfortunately, thiamine levels were not obtained for the patient before treatment was initiated. After administration of IV thiamine, her plasma thiamine level was > 1,200 (normal range, 8-30) nmol/L.

Her differential diagnosis included infectious etiology. Given her leukocytosis and lactic acidosis, vancomycin and piperacillin/tazobactam were started on admission. One day later, her leukocytosis count doubled to 20.7×10⁹ cells/L. However, after 48 hours of negative blood cultures, antibiotics were discontinued.

Small bowel obstruction was suspected due to the patient’s history of abdominal surgery but was ruled out with CT imaging. Similarly, pancreatitis was ruled out based on negative CT imaging and the patient’s normal lipase level. Gastroparesis also was considered because of the patient’s history of hypothyroidism, tobacco use, and her prior gastric-emptying study. The patient was treated for gastroparesis with a course of metoclopramide and erythromycin without improvement in symptoms. Additionally, gastroparesis would not explain the patient’s leukocytosis.

Cannabinoid hyperemesis syndrome (CHS) was suspected because the patient’s symptoms improved with cannabis discontinuation and hot showers.¹ In chronic users, however, tetrahydrocannabinol levels have a half-life of 5 to 13 days.² Although lactic acidosis and leukocytosis have been previously reported with cannabis use, it is unlikely that the patient would have such significant improvement within the first 4 days after discontinuation.^1,3,4 Although the patient had many psychiatric comorbidities with previous hospitalizations describing concern for somatization disorder, her leukocytosis and elevated lactic acid levels were suggestive of an organic rather than a psychiatric etiology of her symptoms.

Discussion

Gastrointestinal beriberi has been reported in chronic cannabis users who present with nausea, vomiting, epigastric pain, leukocytosis, and lactic acidosis; all these symptoms rapidly improve after thiamine administration.^5,6 The patient’s dietary change also eliminated her intake of vitamin B₁₂, which compounded her condition. Thiamine deficiency produces lactic acidosis by disrupting pyruvate metabolism.⁷ Bradycardia also can be a sign of thiamine deficiency, although the patient’s use of clonidine for migraines is a confounder.⁸

Chronically ill patients are prone to nutritional deficiencies, including deficiencies of thiamine.^7,9 Many patients with chronic illnesses also use cannabis to ameliorate physical and neuropsychiatric symptoms.² Recent reports suggest cannabis users are prone to gastrointestinal beriberi and Wernicke encephalopathy.^5,10 Treating gastrointestinal symptoms in these patients can be challenging to diagnose because gastrointestinal beriberi and CHS share many clinical manifestations.

The patient’s presentation is likely multifactorial resulting from the combination of gastrointestinal beriberi and CHS. However, thiamine deficiency seems to play the dominant role.

There is no standard treatment regimen for thiamine deficiency with neurologic deficits, and patients only retain about 10 to 15% of intramuscular (IM) injections of cyanocobalamin.^11,12 The British Committee for Standards in Haematology recommends IM injections of 1,000 mcg of cyanocobalamin 3 times a week for 2 weeks and then reassess the need for continued treatment.¹³ The British Columbia guidelines also recommend IM injections of 1,000 mcg daily for 1 to 5 days before transitioning to oral repletion.¹⁴ European Neurology guidelines for the treatment of Wernicke encephalopathy recommend IV cyanocobalamin 200 mg 3 times daily.¹⁵ Low-level evidence with observational studies informs these decisions and is why there is variation.

The patient’s serum lactate and leukocytosis normalized 1 day after the administration of thiamine. Thiamine deficiency classically causes Wernicke encephalopathy and wet beriberi.¹⁶ The patient did not present with Wernicke encephalopathy’s triad: ophthalmoplegia, ataxia, or confusion. She also was euvolemic without signs or symptoms of wet beriberi.

Conclusions

Thiamine deficiency is principally a clinical diagnosis. Thiamine laboratory testing may not be readily available in all medical centers, and confirming a diagnosis of thiamine deficiency should not delay treatment when thiamine deficiency is suspected. This patient’s thiamine levels resulted a week after collection. The administration of thiamine before sampling also can alter the result as it did in this case. Additionally, laboratories may offer whole blood and serum testing. Whole blood testing is more accurate because most bioactive thiamine is found in red blood cells.¹⁷

A 57-year-old woman with a history of traumatic brain injury, posttraumatic stress disorder, depression, migraines, hypothyroidism, and a hiatal hernia repair presented to the emergency department with a 1-day history of nausea, vomiting, and diffuse abdominal pain. She reported that her symptoms were relieved by hot showers. She also reported having similar symptoms and a previous gastric-emptying study that showed a slow-emptying stomach. Her history also consisted of frequent cannabis use for mood and appetite stimulation along with eliminating meat and fish from her diet, an increase in consumption of simple carbohydrates in the past year, and no alcohol use. Her medications included topiramate 100 mg and clonidine 0.3 mg nightly for migraines; levothyroxine 200 mcg daily for hypothyroidism; tizanidine 4 mg twice a day for muscle spasm; famotidine 40 mg twice a day as needed for gastric reflux; and bupropion 50 mg daily, citalopram 20 mg daily, and lamotrigine 25 mg nightly for mood.

The patient’s physical examination was notable for bradycardia (43 beats/min) and epigastric tenderness. Admission laboratory results were notable for an elevated lactic acid level of 4.8 (normal range, 0.50-2.20) mmol/L and a leukocytosis count of 10.8×10⁹ cells/L. Serum alcohol level and blood cultures were negative. Liver function test, hemoglobin A_1c, and lipase test were unremarkable. Her electrocardiogram showed an unchanged right bundle branch block. Chest X-ray, computed tomography (CT) of her abdomen/pelvis and echocardiogram were unremarkable.

What is your diagnosis? 

How would you treat this patient? 

This patient was diagnosed with gastrointestinal beriberi. Because of her dietary changes, lactic acidosis, and bradycardia, thiamine deficiency was suspected after ruling out other possibilities on the differential diagnosis (Table). The patient’s symptoms resolved after administration of high-dose IV thiamine 500 mg 3 times daily for 4 days. Her white blood cell count and lactic acid level normalized. Unfortunately, thiamine levels were not obtained for the patient before treatment was initiated. After administration of IV thiamine, her plasma thiamine level was > 1,200 (normal range, 8-30) nmol/L.

Her differential diagnosis included infectious etiology. Given her leukocytosis and lactic acidosis, vancomycin and piperacillin/tazobactam were started on admission. One day later, her leukocytosis count doubled to 20.7×10⁹ cells/L. However, after 48 hours of negative blood cultures, antibiotics were discontinued.

Small bowel obstruction was suspected due to the patient’s history of abdominal surgery but was ruled out with CT imaging. Similarly, pancreatitis was ruled out based on negative CT imaging and the patient’s normal lipase level. Gastroparesis also was considered because of the patient’s history of hypothyroidism, tobacco use, and her prior gastric-emptying study. The patient was treated for gastroparesis with a course of metoclopramide and erythromycin without improvement in symptoms. Additionally, gastroparesis would not explain the patient’s leukocytosis.

Cannabinoid hyperemesis syndrome (CHS) was suspected because the patient’s symptoms improved with cannabis discontinuation and hot showers.¹ In chronic users, however, tetrahydrocannabinol levels have a half-life of 5 to 13 days.² Although lactic acidosis and leukocytosis have been previously reported with cannabis use, it is unlikely that the patient would have such significant improvement within the first 4 days after discontinuation.^1,3,4 Although the patient had many psychiatric comorbidities with previous hospitalizations describing concern for somatization disorder, her leukocytosis and elevated lactic acid levels were suggestive of an organic rather than a psychiatric etiology of her symptoms.

Discussion

Gastrointestinal beriberi has been reported in chronic cannabis users who present with nausea, vomiting, epigastric pain, leukocytosis, and lactic acidosis; all these symptoms rapidly improve after thiamine administration.^5,6 The patient’s dietary change also eliminated her intake of vitamin B₁₂, which compounded her condition. Thiamine deficiency produces lactic acidosis by disrupting pyruvate metabolism.⁷ Bradycardia also can be a sign of thiamine deficiency, although the patient’s use of clonidine for migraines is a confounder.⁸

Chronically ill patients are prone to nutritional deficiencies, including deficiencies of thiamine.^7,9 Many patients with chronic illnesses also use cannabis to ameliorate physical and neuropsychiatric symptoms.² Recent reports suggest cannabis users are prone to gastrointestinal beriberi and Wernicke encephalopathy.^5,10 Treating gastrointestinal symptoms in these patients can be challenging to diagnose because gastrointestinal beriberi and CHS share many clinical manifestations.

The patient’s presentation is likely multifactorial resulting from the combination of gastrointestinal beriberi and CHS. However, thiamine deficiency seems to play the dominant role.

There is no standard treatment regimen for thiamine deficiency with neurologic deficits, and patients only retain about 10 to 15% of intramuscular (IM) injections of cyanocobalamin.^11,12 The British Committee for Standards in Haematology recommends IM injections of 1,000 mcg of cyanocobalamin 3 times a week for 2 weeks and then reassess the need for continued treatment.¹³ The British Columbia guidelines also recommend IM injections of 1,000 mcg daily for 1 to 5 days before transitioning to oral repletion.¹⁴ European Neurology guidelines for the treatment of Wernicke encephalopathy recommend IV cyanocobalamin 200 mg 3 times daily.¹⁵ Low-level evidence with observational studies informs these decisions and is why there is variation.

The patient’s serum lactate and leukocytosis normalized 1 day after the administration of thiamine. Thiamine deficiency classically causes Wernicke encephalopathy and wet beriberi.¹⁶ The patient did not present with Wernicke encephalopathy’s triad: ophthalmoplegia, ataxia, or confusion. She also was euvolemic without signs or symptoms of wet beriberi.

Conclusions

Thiamine deficiency is principally a clinical diagnosis. Thiamine laboratory testing may not be readily available in all medical centers, and confirming a diagnosis of thiamine deficiency should not delay treatment when thiamine deficiency is suspected. This patient’s thiamine levels resulted a week after collection. The administration of thiamine before sampling also can alter the result as it did in this case. Additionally, laboratories may offer whole blood and serum testing. Whole blood testing is more accurate because most bioactive thiamine is found in red blood cells.¹⁷

A 57-year-old woman with a history of traumatic brain injury, posttraumatic stress disorder, depression, migraines, hypothyroidism, and a hiatal hernia repair presented to the emergency department with a 1-day history of nausea, vomiting, and diffuse abdominal pain. She reported that her symptoms were relieved by hot showers. She also reported having similar symptoms and a previous gastric-emptying study that showed a slow-emptying stomach. Her history also consisted of frequent cannabis use for mood and appetite stimulation along with eliminating meat and fish from her diet, an increase in consumption of simple carbohydrates in the past year, and no alcohol use. Her medications included topiramate 100 mg and clonidine 0.3 mg nightly for migraines; levothyroxine 200 mcg daily for hypothyroidism; tizanidine 4 mg twice a day for muscle spasm; famotidine 40 mg twice a day as needed for gastric reflux; and bupropion 50 mg daily, citalopram 20 mg daily, and lamotrigine 25 mg nightly for mood.

The patient’s physical examination was notable for bradycardia (43 beats/min) and epigastric tenderness. Admission laboratory results were notable for an elevated lactic acid level of 4.8 (normal range, 0.50-2.20) mmol/L and a leukocytosis count of 10.8×10⁹ cells/L. Serum alcohol level and blood cultures were negative. Liver function test, hemoglobin A_1c, and lipase test were unremarkable. Her electrocardiogram showed an unchanged right bundle branch block. Chest X-ray, computed tomography (CT) of her abdomen/pelvis and echocardiogram were unremarkable.

What is your diagnosis? 

How would you treat this patient? 

This patient was diagnosed with gastrointestinal beriberi. Because of her dietary changes, lactic acidosis, and bradycardia, thiamine deficiency was suspected after ruling out other possibilities on the differential diagnosis (Table). The patient’s symptoms resolved after administration of high-dose IV thiamine 500 mg 3 times daily for 4 days. Her white blood cell count and lactic acid level normalized. Unfortunately, thiamine levels were not obtained for the patient before treatment was initiated. After administration of IV thiamine, her plasma thiamine level was > 1,200 (normal range, 8-30) nmol/L.

Her differential diagnosis included infectious etiology. Given her leukocytosis and lactic acidosis, vancomycin and piperacillin/tazobactam were started on admission. One day later, her leukocytosis count doubled to 20.7×10⁹ cells/L. However, after 48 hours of negative blood cultures, antibiotics were discontinued.

Small bowel obstruction was suspected due to the patient’s history of abdominal surgery but was ruled out with CT imaging. Similarly, pancreatitis was ruled out based on negative CT imaging and the patient’s normal lipase level. Gastroparesis also was considered because of the patient’s history of hypothyroidism, tobacco use, and her prior gastric-emptying study. The patient was treated for gastroparesis with a course of metoclopramide and erythromycin without improvement in symptoms. Additionally, gastroparesis would not explain the patient’s leukocytosis.

Cannabinoid hyperemesis syndrome (CHS) was suspected because the patient’s symptoms improved with cannabis discontinuation and hot showers.¹ In chronic users, however, tetrahydrocannabinol levels have a half-life of 5 to 13 days.² Although lactic acidosis and leukocytosis have been previously reported with cannabis use, it is unlikely that the patient would have such significant improvement within the first 4 days after discontinuation.^1,3,4 Although the patient had many psychiatric comorbidities with previous hospitalizations describing concern for somatization disorder, her leukocytosis and elevated lactic acid levels were suggestive of an organic rather than a psychiatric etiology of her symptoms.

Discussion

Gastrointestinal beriberi has been reported in chronic cannabis users who present with nausea, vomiting, epigastric pain, leukocytosis, and lactic acidosis; all these symptoms rapidly improve after thiamine administration.^5,6 The patient’s dietary change also eliminated her intake of vitamin B₁₂, which compounded her condition. Thiamine deficiency produces lactic acidosis by disrupting pyruvate metabolism.⁷ Bradycardia also can be a sign of thiamine deficiency, although the patient’s use of clonidine for migraines is a confounder.⁸

Chronically ill patients are prone to nutritional deficiencies, including deficiencies of thiamine.^7,9 Many patients with chronic illnesses also use cannabis to ameliorate physical and neuropsychiatric symptoms.² Recent reports suggest cannabis users are prone to gastrointestinal beriberi and Wernicke encephalopathy.^5,10 Treating gastrointestinal symptoms in these patients can be challenging to diagnose because gastrointestinal beriberi and CHS share many clinical manifestations.

The patient’s presentation is likely multifactorial resulting from the combination of gastrointestinal beriberi and CHS. However, thiamine deficiency seems to play the dominant role.

There is no standard treatment regimen for thiamine deficiency with neurologic deficits, and patients only retain about 10 to 15% of intramuscular (IM) injections of cyanocobalamin.^11,12 The British Committee for Standards in Haematology recommends IM injections of 1,000 mcg of cyanocobalamin 3 times a week for 2 weeks and then reassess the need for continued treatment.¹³ The British Columbia guidelines also recommend IM injections of 1,000 mcg daily for 1 to 5 days before transitioning to oral repletion.¹⁴ European Neurology guidelines for the treatment of Wernicke encephalopathy recommend IV cyanocobalamin 200 mg 3 times daily.¹⁵ Low-level evidence with observational studies informs these decisions and is why there is variation.

The patient’s serum lactate and leukocytosis normalized 1 day after the administration of thiamine. Thiamine deficiency classically causes Wernicke encephalopathy and wet beriberi.¹⁶ The patient did not present with Wernicke encephalopathy’s triad: ophthalmoplegia, ataxia, or confusion. She also was euvolemic without signs or symptoms of wet beriberi.

Conclusions

Thiamine deficiency is principally a clinical diagnosis. Thiamine laboratory testing may not be readily available in all medical centers, and confirming a diagnosis of thiamine deficiency should not delay treatment when thiamine deficiency is suspected. This patient’s thiamine levels resulted a week after collection. The administration of thiamine before sampling also can alter the result as it did in this case. Additionally, laboratories may offer whole blood and serum testing. Whole blood testing is more accurate because most bioactive thiamine is found in red blood cells.¹⁷

Exhaustion, numbness, dissociation, and most notably, anger are my emotional response when viewing the video of George Floyd’s death. The homicide trial of former Minneapolis police officer Derek Chauvin activates the shared stress of those who experienced intergenerational trauma and the legacy of racism in the United States of America.

On May 25, 2020, Mr. Floyd died after Derek Chauvin used a lethal maneuver and placed his knee on Mr. Floyd’s neck for 9 minutes and 29 seconds. Mr. Floyd has died physically, but his death is replayed through high-definition social media daily, if not hourly, as I write this article and think of the generational legacy of trauma that African Americans must cope with on an everyday basis. I struggle daily to explain this legacy to my daughters, students, residents, and colleagues. I hope to share with you some of my perspectives on the current trial and give you some insight as to how my training and personal life experience have affected my views on police brutality and the use of lethal force toward African American men.

My earliest recollection of public video-recorded images of police brutality occurred when Rodney King was beaten and assaulted by the Los Angeles Police Department on March 3, 1991. At that time, I was a senior in high school, and the world was different. My clear expectation was that any attempt to resist police arrest would be met with overwhelming and potentially lethal force. This was simply a matter of my daily reality, so, while witnessing the assault of Mr. King, the 17-year-old child didn’t expect much, if any, real change to come about in regard to police brutality. At that time, my mother kept me focused on one singular goal – becoming a physician – and protected me as best she could from the effects of intergenerational trauma woven into the African American experience.

The issue of police brutality and police-involved deaths has been recognized as a significant public health concern for some time. Over the 3 decades since the assault on Mr. King, several researchers have examined these issues. A review of all the research is beyond the scope of this opinion piece. Still, I will highlight a study that I believe illustrates some conclusions scholars have come to regarding police use of lethal force and subsequent mortality in African American men. A recent study by Frank Edwards, PhD, and colleagues, published in the Proceedings of the National Academy of Sciences, showed that Black men were 2.5 times more likely to be killed by police over their life course than White men.

The researchers also developed predictive models that about 1 in 1,000 Black men and boys will be killed by police over their life course, and that among all age groups Black men and boys face the highest lifetime risk. The authors concluded that “Our analysis shows that the risk of being killed by police is jointly patterned by one’s race, gender, and age. Police violence is a leading cause of death for young men, and young men of color face an exceptionally high risk of being killed by police. Inequalities in risk are pronounced throughout the life course. This study reinforces calls to treat police violence as a public health issue.”

Research such as this helps validate on a visceral level what I already was taught: “As a Black male, encounters with police can quickly become deadly, and you must remain calm, or you could die.” This thought process informed much of my thinking whenever I heard about a Black male being fatally shot by police. My first response was to ask, “Was he resisting arrest?” At this time, my naive impression was that “if you don’t resist or conflict, you’ll live.” It wasn’t until my training in psychiatry that I realized that the duty to calm, support, and most importantly, protect was the responsibility of the person who is given the trust of the public. As a psychiatrist, I am humbled by the trust the public places in physicians to restrain patients and take part in their involuntary hospitalizations. Over the years, I learned from my attending physicians, colleagues in security, social work, nursing, assertive community treatment (ACT) teams, and many other allied health professions that the responsibility to show restraint, calm, and compassion lies with those who have the power and trust of the public.

Mostly, I learned from my patients. They taught me to meet distress with compassion and humanity and not simply with force. With those lessons in mind, I now fast forward to July 17, 2014, and the death of Eric Garner. On July 17, New York Police Department officers approached Mr. Garner on the suspicion that he was selling loose cigarettes. Amid this encounter, Mr. Garner was subjected to a chokehold, and his face was pinned to the ground while he can be heard saying, “I can’t breathe.” At this time in my professional career, I had just become a dean of student affairs at the George Washington School of Medicine and Health Sciences. I can still remember the response of my minority students, and the sense of pain and anguish they felt watching the video of a chokehold being used on a man stating, “I can’t breathe.” At this point, my training would not allow me to see this as anything other than an unnecessary use of lethal force that would subsequently be ruled a homicide. I hoped that we as a nation had reached a “reckoning “ because of Mr. Garner’s death and Michael Brown Jr.’s subsequent death in Ferguson, Mo., in St. Louis County, on Aug. 9, 2014. I hoped we were ready to finally address police brutality and excessive use of force that had disproportionately affected Black men. I was utterly wrong. Black men such as Alton Sterling, Jamar Clark, and many others would die in fatal police encounters. So would Tamir Rice, who was 12 years old when he was shot and killed by a police officer.

This brings me back to the death of Mr. Floyd. As I listened to the witnesses’ testimony, it triggered an emotional response from sadness, fear, shock, but mostly anger. Some would consider it progress that the Minneapolis Police Department’s top homicide detective testified that kneeling on Mr. Floyd’s neck after he had been restrained was “unnecessary.” The officer stated, “If your knee is on someone’s neck, that could kill him.” While I acknowledge this is a form of progress, we must ultimately address the other “substantial causal factor of death” for Mr. Floyd. Namely, the systemic racism present in a criminal justice system in the form of policies and procedures that allow for continued racial disparities and inequities.

There will be coverage of the court proceedings and a detailed dissection of the legal arguments. Questions regarding Mr. Floyd’s physical health and struggle with opiate use disorder will be raised by the defense. The debate about the substantial causal factor will be played out in the court and the media. Ultimately, we, as health professionals, need to ask ourselves, “Who has the power and the duty to do no harm?”

Dr. Norris is associate dean of student affairs and administration at George Washington University, Washington. He has no disclosures.

Exhaustion, numbness, dissociation, and most notably, anger are my emotional response when viewing the video of George Floyd’s death. The homicide trial of former Minneapolis police officer Derek Chauvin activates the shared stress of those who experienced intergenerational trauma and the legacy of racism in the United States of America.

On May 25, 2020, Mr. Floyd died after Derek Chauvin used a lethal maneuver and placed his knee on Mr. Floyd’s neck for 9 minutes and 29 seconds. Mr. Floyd has died physically, but his death is replayed through high-definition social media daily, if not hourly, as I write this article and think of the generational legacy of trauma that African Americans must cope with on an everyday basis. I struggle daily to explain this legacy to my daughters, students, residents, and colleagues. I hope to share with you some of my perspectives on the current trial and give you some insight as to how my training and personal life experience have affected my views on police brutality and the use of lethal force toward African American men.

My earliest recollection of public video-recorded images of police brutality occurred when Rodney King was beaten and assaulted by the Los Angeles Police Department on March 3, 1991. At that time, I was a senior in high school, and the world was different. My clear expectation was that any attempt to resist police arrest would be met with overwhelming and potentially lethal force. This was simply a matter of my daily reality, so, while witnessing the assault of Mr. King, the 17-year-old child didn’t expect much, if any, real change to come about in regard to police brutality. At that time, my mother kept me focused on one singular goal – becoming a physician – and protected me as best she could from the effects of intergenerational trauma woven into the African American experience.

The issue of police brutality and police-involved deaths has been recognized as a significant public health concern for some time. Over the 3 decades since the assault on Mr. King, several researchers have examined these issues. A review of all the research is beyond the scope of this opinion piece. Still, I will highlight a study that I believe illustrates some conclusions scholars have come to regarding police use of lethal force and subsequent mortality in African American men. A recent study by Frank Edwards, PhD, and colleagues, published in the Proceedings of the National Academy of Sciences, showed that Black men were 2.5 times more likely to be killed by police over their life course than White men.

The researchers also developed predictive models that about 1 in 1,000 Black men and boys will be killed by police over their life course, and that among all age groups Black men and boys face the highest lifetime risk. The authors concluded that “Our analysis shows that the risk of being killed by police is jointly patterned by one’s race, gender, and age. Police violence is a leading cause of death for young men, and young men of color face an exceptionally high risk of being killed by police. Inequalities in risk are pronounced throughout the life course. This study reinforces calls to treat police violence as a public health issue.”

Research such as this helps validate on a visceral level what I already was taught: “As a Black male, encounters with police can quickly become deadly, and you must remain calm, or you could die.” This thought process informed much of my thinking whenever I heard about a Black male being fatally shot by police. My first response was to ask, “Was he resisting arrest?” At this time, my naive impression was that “if you don’t resist or conflict, you’ll live.” It wasn’t until my training in psychiatry that I realized that the duty to calm, support, and most importantly, protect was the responsibility of the person who is given the trust of the public. As a psychiatrist, I am humbled by the trust the public places in physicians to restrain patients and take part in their involuntary hospitalizations. Over the years, I learned from my attending physicians, colleagues in security, social work, nursing, assertive community treatment (ACT) teams, and many other allied health professions that the responsibility to show restraint, calm, and compassion lies with those who have the power and trust of the public.

Mostly, I learned from my patients. They taught me to meet distress with compassion and humanity and not simply with force. With those lessons in mind, I now fast forward to July 17, 2014, and the death of Eric Garner. On July 17, New York Police Department officers approached Mr. Garner on the suspicion that he was selling loose cigarettes. Amid this encounter, Mr. Garner was subjected to a chokehold, and his face was pinned to the ground while he can be heard saying, “I can’t breathe.” At this time in my professional career, I had just become a dean of student affairs at the George Washington School of Medicine and Health Sciences. I can still remember the response of my minority students, and the sense of pain and anguish they felt watching the video of a chokehold being used on a man stating, “I can’t breathe.” At this point, my training would not allow me to see this as anything other than an unnecessary use of lethal force that would subsequently be ruled a homicide. I hoped that we as a nation had reached a “reckoning “ because of Mr. Garner’s death and Michael Brown Jr.’s subsequent death in Ferguson, Mo., in St. Louis County, on Aug. 9, 2014. I hoped we were ready to finally address police brutality and excessive use of force that had disproportionately affected Black men. I was utterly wrong. Black men such as Alton Sterling, Jamar Clark, and many others would die in fatal police encounters. So would Tamir Rice, who was 12 years old when he was shot and killed by a police officer.

This brings me back to the death of Mr. Floyd. As I listened to the witnesses’ testimony, it triggered an emotional response from sadness, fear, shock, but mostly anger. Some would consider it progress that the Minneapolis Police Department’s top homicide detective testified that kneeling on Mr. Floyd’s neck after he had been restrained was “unnecessary.” The officer stated, “If your knee is on someone’s neck, that could kill him.” While I acknowledge this is a form of progress, we must ultimately address the other “substantial causal factor of death” for Mr. Floyd. Namely, the systemic racism present in a criminal justice system in the form of policies and procedures that allow for continued racial disparities and inequities.

There will be coverage of the court proceedings and a detailed dissection of the legal arguments. Questions regarding Mr. Floyd’s physical health and struggle with opiate use disorder will be raised by the defense. The debate about the substantial causal factor will be played out in the court and the media. Ultimately, we, as health professionals, need to ask ourselves, “Who has the power and the duty to do no harm?”

Dr. Norris is associate dean of student affairs and administration at George Washington University, Washington. He has no disclosures.

Exhaustion, numbness, dissociation, and most notably, anger are my emotional response when viewing the video of George Floyd’s death. The homicide trial of former Minneapolis police officer Derek Chauvin activates the shared stress of those who experienced intergenerational trauma and the legacy of racism in the United States of America.

On May 25, 2020, Mr. Floyd died after Derek Chauvin used a lethal maneuver and placed his knee on Mr. Floyd’s neck for 9 minutes and 29 seconds. Mr. Floyd has died physically, but his death is replayed through high-definition social media daily, if not hourly, as I write this article and think of the generational legacy of trauma that African Americans must cope with on an everyday basis. I struggle daily to explain this legacy to my daughters, students, residents, and colleagues. I hope to share with you some of my perspectives on the current trial and give you some insight as to how my training and personal life experience have affected my views on police brutality and the use of lethal force toward African American men.

My earliest recollection of public video-recorded images of police brutality occurred when Rodney King was beaten and assaulted by the Los Angeles Police Department on March 3, 1991. At that time, I was a senior in high school, and the world was different. My clear expectation was that any attempt to resist police arrest would be met with overwhelming and potentially lethal force. This was simply a matter of my daily reality, so, while witnessing the assault of Mr. King, the 17-year-old child didn’t expect much, if any, real change to come about in regard to police brutality. At that time, my mother kept me focused on one singular goal – becoming a physician – and protected me as best she could from the effects of intergenerational trauma woven into the African American experience.

The issue of police brutality and police-involved deaths has been recognized as a significant public health concern for some time. Over the 3 decades since the assault on Mr. King, several researchers have examined these issues. A review of all the research is beyond the scope of this opinion piece. Still, I will highlight a study that I believe illustrates some conclusions scholars have come to regarding police use of lethal force and subsequent mortality in African American men. A recent study by Frank Edwards, PhD, and colleagues, published in the Proceedings of the National Academy of Sciences, showed that Black men were 2.5 times more likely to be killed by police over their life course than White men.

The researchers also developed predictive models that about 1 in 1,000 Black men and boys will be killed by police over their life course, and that among all age groups Black men and boys face the highest lifetime risk. The authors concluded that “Our analysis shows that the risk of being killed by police is jointly patterned by one’s race, gender, and age. Police violence is a leading cause of death for young men, and young men of color face an exceptionally high risk of being killed by police. Inequalities in risk are pronounced throughout the life course. This study reinforces calls to treat police violence as a public health issue.”

Research such as this helps validate on a visceral level what I already was taught: “As a Black male, encounters with police can quickly become deadly, and you must remain calm, or you could die.” This thought process informed much of my thinking whenever I heard about a Black male being fatally shot by police. My first response was to ask, “Was he resisting arrest?” At this time, my naive impression was that “if you don’t resist or conflict, you’ll live.” It wasn’t until my training in psychiatry that I realized that the duty to calm, support, and most importantly, protect was the responsibility of the person who is given the trust of the public. As a psychiatrist, I am humbled by the trust the public places in physicians to restrain patients and take part in their involuntary hospitalizations. Over the years, I learned from my attending physicians, colleagues in security, social work, nursing, assertive community treatment (ACT) teams, and many other allied health professions that the responsibility to show restraint, calm, and compassion lies with those who have the power and trust of the public.

Mostly, I learned from my patients. They taught me to meet distress with compassion and humanity and not simply with force. With those lessons in mind, I now fast forward to July 17, 2014, and the death of Eric Garner. On July 17, New York Police Department officers approached Mr. Garner on the suspicion that he was selling loose cigarettes. Amid this encounter, Mr. Garner was subjected to a chokehold, and his face was pinned to the ground while he can be heard saying, “I can’t breathe.” At this time in my professional career, I had just become a dean of student affairs at the George Washington School of Medicine and Health Sciences. I can still remember the response of my minority students, and the sense of pain and anguish they felt watching the video of a chokehold being used on a man stating, “I can’t breathe.” At this point, my training would not allow me to see this as anything other than an unnecessary use of lethal force that would subsequently be ruled a homicide. I hoped that we as a nation had reached a “reckoning “ because of Mr. Garner’s death and Michael Brown Jr.’s subsequent death in Ferguson, Mo., in St. Louis County, on Aug. 9, 2014. I hoped we were ready to finally address police brutality and excessive use of force that had disproportionately affected Black men. I was utterly wrong. Black men such as Alton Sterling, Jamar Clark, and many others would die in fatal police encounters. So would Tamir Rice, who was 12 years old when he was shot and killed by a police officer.

This brings me back to the death of Mr. Floyd. As I listened to the witnesses’ testimony, it triggered an emotional response from sadness, fear, shock, but mostly anger. Some would consider it progress that the Minneapolis Police Department’s top homicide detective testified that kneeling on Mr. Floyd’s neck after he had been restrained was “unnecessary.” The officer stated, “If your knee is on someone’s neck, that could kill him.” While I acknowledge this is a form of progress, we must ultimately address the other “substantial causal factor of death” for Mr. Floyd. Namely, the systemic racism present in a criminal justice system in the form of policies and procedures that allow for continued racial disparities and inequities.

There will be coverage of the court proceedings and a detailed dissection of the legal arguments. Questions regarding Mr. Floyd’s physical health and struggle with opiate use disorder will be raised by the defense. The debate about the substantial causal factor will be played out in the court and the media. Ultimately, we, as health professionals, need to ask ourselves, “Who has the power and the duty to do no harm?”

Dr. Norris is associate dean of student affairs and administration at George Washington University, Washington. He has no disclosures.

In 1967, when the United Nations Convention on Drugs classified psychedelics as schedule I substances, it effectively ended research into these agents as potential therapeutics for psychiatric disorders.

eskymaks/iStock/Getty Images

Psychedelics induce altered states of perception. They bind to the 5-hydroxytryptamine 2A (5-HT2A) receptor and include psilocybin, which is derived from “magic mushrooms”; N,N-dimethyltryptamine (DMT), a component of ayahuasca and mescaline (peyote cactus); and the synthesized compound D-lysergic acid diethylamide (LSD). Other agents, such as ketamine and 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy, are sometimes considered psychedelics as well.

Before they were classified as schedule I agents, psychedelics had been shown to be particularly beneficial for patients with treatment-resistant conditions, including depression and posttraumatic stress disorder (PTSD), especially when administered in a supportive, therapeutic setting.

Now, after a hiatus of almost 50 years, there is renewed global interest in the scientific investigation of psychedelics. The attention was spurred in part by several exploratory studies of DMT in humans conducted in the 1990s by Rick Strassman, MD, and colleagues at the University of New Mexico, Albuquerque.

Around the same time, Franz X. Vollenweider, MD, and colleagues at the University of Zürich began researching psilocybin and its effects on human behavior. However, it was a 2006 study of psilocybin by a team of researchers at Johns Hopkins University, Baltimore, that is widely cited as a catalyst for the current renaissance in psychedelic research.

To provide a broad-based, international perspective on these agents, including their current legal status and indications, treatment regimens, safety, efficacy, and future considerations, this news organization interviewed nine expert researchers from around the globe.
 

Global legal status

In most, if not all, countries, it is still illegal to prescribe psychedelics in other than a research setting.

In the United States, classic psychedelics remain schedule I substances and therefore are unavailable for clinical use. They can be used in research, but only with approval from the Food and Drug Administration under licensure from the Drug Enforcement Administration.

France lists all synthetic hallucinogens and hallucinogenic mushrooms as narcotic. As a result, possession, use, transportation, and collection are subject to criminal sanctions.

In France, NMDA antagonists such as ketamine and nitrous oxide are regarded as psychedelic molecules and can be used off label for various conditions or as part of research protocols authorized by the French public health code.

Although psychedelics are illegal under Mexican law, they are commonly used in indigenous communities as part of traditional rituals.

“The line between traditional consumption and psychedelic tourism is very thin,” José J. Mendoza Velásquez, MD, professor in the department of mental health, National Autonomous University of Mexico, Mexico City, said in an interview.

Psychedelics also are illegal in the United Kingdom, although government agencies have recently allowed research groups to investigate them. Psychedelics cannot be prescribed in Germany, Spain, or Italy. However, investigators in these countries can request permission from regulatory agencies to conduct research.

Brazil allows psychedelic substances to be researched, particularly ayahuasca, which has long traditional and religious roots in the country.

However, as in other countries, none of the classic psychedelics is regulated for therapeutic use in Brazil. It is widely expected that the Brazilian government will approve MDMA sometime in 2024 for use in the treatment of PTSD.
 

Potential indications

Psychedelics are currently under investigation as potential treatments for major depression, treatment-resistant depression, PTSD, pain management, and anorexia, among other conditions.

In France, Florian Ferreri, MD, PhD, at Hospital Saint-Antoine, Paris, is researching ketamine for treatment of patients with suicidal crisis/ideation and treatment-resistant depression.

In the United Kingdom, David Nutt, FMedSci, Edmond J. Safra Professor of Neuropsychopharmacology at Imperial College London, and his team have conducted studies of the use of psychedelics in conjunction with psychological support for patients with treatment-resistant depression, and they are currently exploring their use in the treatment of anorexia and various pain syndromes.

In Germany, Gerhard Gründer, MD, professor of psychiatry at the Central Institute of Mental Health, in Mannheim, noted that a study of psilocybin for treatment-resistant depression will launch sometime in 2021. In Italy, current research is focusing on MDMA and ketamine in the laboratory environment and in animal models for treating depression and drug abuse.

Researcher Helen Dolengevich-Segal, MD, a psychiatrist at Hospital Universitario del Henares, Madrid, noted that although research on esketamine for the treatment of severe depressive disorder with suicidal thoughts is underway, there is very limited published research from that country into the use of classic psychedelics for various psychiatric disorders, given their current illegal status.

Mexico’s Dr. Velásquez noted that although he is prohibited from prescribing psychedelics, he does have patients who take the drugs to augment medical treatment. For instance, he said, his patients frequently use psilocybin to help with severe depression, pain, and insomnia.
 

Environment is key

Most researchers agree that for psychedelics to be safe and effective, patient education and administration in a controlled environment by experienced clinicians are key to successful treatment.

Roland R. Griffiths, PhD, director of the Center for Psychedelic and Consciousness Research at Johns Hopkins, said that ongoing U.S. psilocybin research – primarily in major depressive disorder and psychological distress associated with life-threatening illness, drug addiction, anorexia nervosa, obsessive-compulsive disorder, and headache – generally includes one or two treatment sessions, each of which lasts 6-8 hours.

Such sessions typically involve oral administration of a moderately high dose of a psychedelic under what he characterizes as “psychologically supported conditions.”

For Dr. Griffiths, there are serious potential risks associated with the use of psilocybin and other psychedelics outside such environments.

“When taken in uncontrolled conditions, classic psychedelics can produce confusion and disorientation resulting in behavior dangerous to the participant and others, including life-threatening risk,” he said.

Dr. Gründer agreed.

“At the moment, I cannot imagine that you would go to the pharmacy with a prescription for psilocybin and get yourself a pill and then take it in a quiet little room,” he said. Dr. Dolengevich-Segal and Dr. Velásquez echoed these sentiments, noting the optimal location for administration is one that is quiet and secure and where patients feel safe.

Luís Fernando Tófoli, MD, PhD, professor of medical psychology and psychiatry at the University of Campinas, and Eduardo Schenberg, PhD, founder and CEO of Instituto Phaneros in São Paulo, Brazil, said more research is needed to determine the optimal therapeutic environment for individual agents.

“Most studies have a low number of participants (around 20 or 30), especially in neuroimaging, with high unblinding rates,” Dr. Schenberg said. “Therefore, novel methodological approaches are also necessary, as these substances do not easily fit into the traditional pharmacology epistemic model.”
 

Risks, abuse potential

The abuse potential of psychedelics is an ongoing concern for the public, researchers, and regulators, but the consensus among nearly all of these experts is that when administered by medical professionals in controlled settings, these drugs are associated with extremely low risk.

It is recreational use that presents an abuse concern, said Dr. Ferreri, but with the low doses used in psychiatry, the risk is “very limited or even nonexistent.”

Dr. Nutt said the abuse potential of psychedelics is so low that they can be used to treat addiction.

“Functionally, psychedelics are antiaddictive,” Dr. Nutt said. “The fact is, if you take them repeatedly, you develop tolerance, and the effect disappears. You can’t overcome it. But everyone believes they’re addictive because they’re scheduled drugs.”

Dr. Velásquez is something of an outlier. He believes the abuse potential with psychedelics is poorly understood and that some patients may develop tolerance, which is a potential gateway to dependence.

“Such is the case with LSD,” he said, “where this substance also favors tolerance to other psychedelic drugs such as psilocybin.”

Dosing also seems to play a key role in mitigating potential abuse, said Luca Pani, MD, professor of pharmacology and psychiatry at the University of Modena, Italy. Dr. Pani explained that with low doses and microdoses of psychedelics, the potential for abuse is eliminated.

Dr. Nutt, Dr. Pani, and Dr. Ferreri also noted the importance of medical supervision. For instance, said Dr. Ferreri, when administering ketamine, his team closely monitors both mental and physical parameters – heart rate and blood pressure, in particular – because the drug can have hypertensive effects.

Dr. Schenberg noted that ibogaine, a naturally occurring psychedelic frequently used by traditional communities in Africa in rituals and for healing purposes, could cause potentially fatal arrhythmias, so it’s critical that the treatment is administered in a hospital setting that has a cardiac unit.

Dr. Pani said there is a need for more research, especially regarding the molecular mechanisms behind the behavioral effects of low-dose psychedelic therapy and the potential risks of multiple treatments with the drugs.

“Although extensive toxicology has been conducted on a single active dose of psilocybin, which has been proven to be safe, further research is required to understand better the possible health risks, especially in relation to cardiac and lung tissue,” he said.
 

Psychologically challenging

The experts note that given the relative lack of experience with psychedelic therapy, preparing patients for potential adverse effects is paramount. This is particularly relevant in the research setting and highlights the need for adequate patient screening and aftercare.

Dr. Gründer and Dr. Dolengevich-Segal emphasized the importance of having qualified personnel available in the event that patients experience adverse psychological events during treatment.

For Dr. Gründer, the potential for psilocybin to cause patients to lose control, experience psychotic symptoms, or become paranoid warrants considerable preparation by treating physicians.

Patients occasionally experience fear and anxiety during treatment, though it’s usually short-lived, said Dr. Griffiths. Nevertheless, these experiences may open the door to greater insight. “A number of people report that these psychologically challenging states are a valuable part of the overall experience,” he said.

The situation is similar in Spain, where Dr. Dolengevich-Segal noted that typical treatment regimens have a strong focus on the patient’s experience as a therapeutic tool. As in the United Kingdom and the United States, her team guides patients to what they call a “peak experience,” which allows them to gain a better understanding of the trauma underlying their mental health problems.

Dr. Nutt said that in the United Kingdom, they haven’t seen adverse reactions in patients receiving psychedelic therapy, although sedatives such as benzodiazepines could be used to manage them. He added that at his center, two therapists are present at every treatment session, and all personnel are “trained medics or psychologists.”
 

Patient education

Preparing and educating patients about the therapy are critical, said Dr. Gründer, especially given the intense response psychedelic treatment often invokes.

Echoing Dr. Gründer, Dr. Tófoli said explaining the nature of psychedelic treatment to potential patients helps ease anxiety.

Dr. Griffiths noted that in the United States, study participants are not only educated about the potential effects of psychedelic agents but also undergo several hours of psychological preparation in advance of their first treatment session and are provided with psychological support after treatment.

There is also a strong emphasis on patient preparation and education in the United Kingdom, where patients meet with therapists before and after treatment. During these posttreatment debriefings, clinicians use the patients’ experience with psychedelics to help them gain insight into the underlying cause of their depression.

Dr. Schenberg noted that at his institution in São Paulo, there are online courses to teach clinicians about psychedelic therapy for psychiatric disorders. Next year, he added, a new training program in MDMA-assisted psychotherapy will begin.
 

Working out treatment protocols

Treatment protocols for psychedelics vary by agent and indication from country to country. For instance, Dr. Pani noted that current psychedelic research in Italy predominantly focuses more on microdosing, which involves administering 1% of the pharmacologically active dose to a maximum of 100 mcg, in contrast to low dosing or full dosing.

Therapeutic regimens in Brazil, said Dr. Schenberg, also differ by agent but share common elements. For instance, psychedelics are always administered in a research setting, and sessions include concomitant psychotherapy.

In Germany, investigators are working to determine optimal treatment regimen for psilocybin for resistant depression in a randomized three-arm study planned for 2021.

For Mexico’s Dr. Velásquez, treatment regimens are complex and varied. Either way, he said, patients always require long-term follow-up.

With ketamine therapy, Dr. Ferreri said his team administers the drug in 45- to 60-minute intravenous infusion sessions in a hospital room without light or sound stimulation. Regardless of the drug’s immediate effect, he said, the protocol is repeated within a 6-month period.

The question of the duration of treatment effect is important. Dr. Griffiths said research suggests that the positive effects of psilocybin are long lasting and that most individuals report positive changes in mood, attitude, and behavior that endure for months or even years after the session.

“Our research has shown that the benefits of these experiences can last as long as 14 months, often longer, and that many participants characterize their psilocybin experience as among the most profound and personally meaningful experiences of their lives,” said Dr. Griffiths.

Dr. Nutt agreed, noting that a single intense “trip” can improve mood for weeks, months, or even years. Nevertheless, he said, in his experience, approximately three-quarters of patients treated with psychedelics for major depression relapse within 3-9 months.

“Most get better,” he said, “but the majority of depression comes back over a period of months.”

Given the current illegal status of the drugs, he said it’s nearly impossible to provide patients with regular, subsequent treatment with psychedelics over time.

“My suspicion is that you might well have to dose four or five times over a couple of years to get people to escape from very severe depression,” said Dr. Nutt. “The longer they’ve been depressed, the harder it is for them to make a full recovery, because it’s more entrenched in the brain.”

All experts agree that exciting times are ahead for psychedelics as therapeutics for a wide range of psychiatric disorders.

“We can look forward to continued growth and expansion of this research,” said Dr. Griffiths, “including the refinement of protocols for a variety of therapeutic indications and to the development of a variety of new classic psychedelic compounds.”

A version of this article first appeared on Medscape.com.

In 1967, when the United Nations Convention on Drugs classified psychedelics as schedule I substances, it effectively ended research into these agents as potential therapeutics for psychiatric disorders.

eskymaks/iStock/Getty Images

Psychedelics induce altered states of perception. They bind to the 5-hydroxytryptamine 2A (5-HT2A) receptor and include psilocybin, which is derived from “magic mushrooms”; N,N-dimethyltryptamine (DMT), a component of ayahuasca and mescaline (peyote cactus); and the synthesized compound D-lysergic acid diethylamide (LSD). Other agents, such as ketamine and 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy, are sometimes considered psychedelics as well.

Before they were classified as schedule I agents, psychedelics had been shown to be particularly beneficial for patients with treatment-resistant conditions, including depression and posttraumatic stress disorder (PTSD), especially when administered in a supportive, therapeutic setting.

Now, after a hiatus of almost 50 years, there is renewed global interest in the scientific investigation of psychedelics. The attention was spurred in part by several exploratory studies of DMT in humans conducted in the 1990s by Rick Strassman, MD, and colleagues at the University of New Mexico, Albuquerque.

Around the same time, Franz X. Vollenweider, MD, and colleagues at the University of Zürich began researching psilocybin and its effects on human behavior. However, it was a 2006 study of psilocybin by a team of researchers at Johns Hopkins University, Baltimore, that is widely cited as a catalyst for the current renaissance in psychedelic research.

To provide a broad-based, international perspective on these agents, including their current legal status and indications, treatment regimens, safety, efficacy, and future considerations, this news organization interviewed nine expert researchers from around the globe.
 

Global legal status

In most, if not all, countries, it is still illegal to prescribe psychedelics in other than a research setting.

In the United States, classic psychedelics remain schedule I substances and therefore are unavailable for clinical use. They can be used in research, but only with approval from the Food and Drug Administration under licensure from the Drug Enforcement Administration.

France lists all synthetic hallucinogens and hallucinogenic mushrooms as narcotic. As a result, possession, use, transportation, and collection are subject to criminal sanctions.

In France, NMDA antagonists such as ketamine and nitrous oxide are regarded as psychedelic molecules and can be used off label for various conditions or as part of research protocols authorized by the French public health code.

Although psychedelics are illegal under Mexican law, they are commonly used in indigenous communities as part of traditional rituals.

“The line between traditional consumption and psychedelic tourism is very thin,” José J. Mendoza Velásquez, MD, professor in the department of mental health, National Autonomous University of Mexico, Mexico City, said in an interview.

Psychedelics also are illegal in the United Kingdom, although government agencies have recently allowed research groups to investigate them. Psychedelics cannot be prescribed in Germany, Spain, or Italy. However, investigators in these countries can request permission from regulatory agencies to conduct research.

Brazil allows psychedelic substances to be researched, particularly ayahuasca, which has long traditional and religious roots in the country.

However, as in other countries, none of the classic psychedelics is regulated for therapeutic use in Brazil. It is widely expected that the Brazilian government will approve MDMA sometime in 2024 for use in the treatment of PTSD.
 

Potential indications

Psychedelics are currently under investigation as potential treatments for major depression, treatment-resistant depression, PTSD, pain management, and anorexia, among other conditions.

In France, Florian Ferreri, MD, PhD, at Hospital Saint-Antoine, Paris, is researching ketamine for treatment of patients with suicidal crisis/ideation and treatment-resistant depression.

In the United Kingdom, David Nutt, FMedSci, Edmond J. Safra Professor of Neuropsychopharmacology at Imperial College London, and his team have conducted studies of the use of psychedelics in conjunction with psychological support for patients with treatment-resistant depression, and they are currently exploring their use in the treatment of anorexia and various pain syndromes.

In Germany, Gerhard Gründer, MD, professor of psychiatry at the Central Institute of Mental Health, in Mannheim, noted that a study of psilocybin for treatment-resistant depression will launch sometime in 2021. In Italy, current research is focusing on MDMA and ketamine in the laboratory environment and in animal models for treating depression and drug abuse.

Researcher Helen Dolengevich-Segal, MD, a psychiatrist at Hospital Universitario del Henares, Madrid, noted that although research on esketamine for the treatment of severe depressive disorder with suicidal thoughts is underway, there is very limited published research from that country into the use of classic psychedelics for various psychiatric disorders, given their current illegal status.

Mexico’s Dr. Velásquez noted that although he is prohibited from prescribing psychedelics, he does have patients who take the drugs to augment medical treatment. For instance, he said, his patients frequently use psilocybin to help with severe depression, pain, and insomnia.
 

Environment is key

Most researchers agree that for psychedelics to be safe and effective, patient education and administration in a controlled environment by experienced clinicians are key to successful treatment.

Roland R. Griffiths, PhD, director of the Center for Psychedelic and Consciousness Research at Johns Hopkins, said that ongoing U.S. psilocybin research – primarily in major depressive disorder and psychological distress associated with life-threatening illness, drug addiction, anorexia nervosa, obsessive-compulsive disorder, and headache – generally includes one or two treatment sessions, each of which lasts 6-8 hours.

Such sessions typically involve oral administration of a moderately high dose of a psychedelic under what he characterizes as “psychologically supported conditions.”

For Dr. Griffiths, there are serious potential risks associated with the use of psilocybin and other psychedelics outside such environments.

“When taken in uncontrolled conditions, classic psychedelics can produce confusion and disorientation resulting in behavior dangerous to the participant and others, including life-threatening risk,” he said.

Dr. Gründer agreed.

“At the moment, I cannot imagine that you would go to the pharmacy with a prescription for psilocybin and get yourself a pill and then take it in a quiet little room,” he said. Dr. Dolengevich-Segal and Dr. Velásquez echoed these sentiments, noting the optimal location for administration is one that is quiet and secure and where patients feel safe.

Luís Fernando Tófoli, MD, PhD, professor of medical psychology and psychiatry at the University of Campinas, and Eduardo Schenberg, PhD, founder and CEO of Instituto Phaneros in São Paulo, Brazil, said more research is needed to determine the optimal therapeutic environment for individual agents.

“Most studies have a low number of participants (around 20 or 30), especially in neuroimaging, with high unblinding rates,” Dr. Schenberg said. “Therefore, novel methodological approaches are also necessary, as these substances do not easily fit into the traditional pharmacology epistemic model.”
 

Risks, abuse potential

The abuse potential of psychedelics is an ongoing concern for the public, researchers, and regulators, but the consensus among nearly all of these experts is that when administered by medical professionals in controlled settings, these drugs are associated with extremely low risk.

It is recreational use that presents an abuse concern, said Dr. Ferreri, but with the low doses used in psychiatry, the risk is “very limited or even nonexistent.”

Dr. Nutt said the abuse potential of psychedelics is so low that they can be used to treat addiction.

“Functionally, psychedelics are antiaddictive,” Dr. Nutt said. “The fact is, if you take them repeatedly, you develop tolerance, and the effect disappears. You can’t overcome it. But everyone believes they’re addictive because they’re scheduled drugs.”

Dr. Velásquez is something of an outlier. He believes the abuse potential with psychedelics is poorly understood and that some patients may develop tolerance, which is a potential gateway to dependence.

“Such is the case with LSD,” he said, “where this substance also favors tolerance to other psychedelic drugs such as psilocybin.”

Dosing also seems to play a key role in mitigating potential abuse, said Luca Pani, MD, professor of pharmacology and psychiatry at the University of Modena, Italy. Dr. Pani explained that with low doses and microdoses of psychedelics, the potential for abuse is eliminated.

Dr. Nutt, Dr. Pani, and Dr. Ferreri also noted the importance of medical supervision. For instance, said Dr. Ferreri, when administering ketamine, his team closely monitors both mental and physical parameters – heart rate and blood pressure, in particular – because the drug can have hypertensive effects.

Dr. Schenberg noted that ibogaine, a naturally occurring psychedelic frequently used by traditional communities in Africa in rituals and for healing purposes, could cause potentially fatal arrhythmias, so it’s critical that the treatment is administered in a hospital setting that has a cardiac unit.

Dr. Pani said there is a need for more research, especially regarding the molecular mechanisms behind the behavioral effects of low-dose psychedelic therapy and the potential risks of multiple treatments with the drugs.

“Although extensive toxicology has been conducted on a single active dose of psilocybin, which has been proven to be safe, further research is required to understand better the possible health risks, especially in relation to cardiac and lung tissue,” he said.
 

Psychologically challenging

The experts note that given the relative lack of experience with psychedelic therapy, preparing patients for potential adverse effects is paramount. This is particularly relevant in the research setting and highlights the need for adequate patient screening and aftercare.

Dr. Gründer and Dr. Dolengevich-Segal emphasized the importance of having qualified personnel available in the event that patients experience adverse psychological events during treatment.

For Dr. Gründer, the potential for psilocybin to cause patients to lose control, experience psychotic symptoms, or become paranoid warrants considerable preparation by treating physicians.

Patients occasionally experience fear and anxiety during treatment, though it’s usually short-lived, said Dr. Griffiths. Nevertheless, these experiences may open the door to greater insight. “A number of people report that these psychologically challenging states are a valuable part of the overall experience,” he said.

The situation is similar in Spain, where Dr. Dolengevich-Segal noted that typical treatment regimens have a strong focus on the patient’s experience as a therapeutic tool. As in the United Kingdom and the United States, her team guides patients to what they call a “peak experience,” which allows them to gain a better understanding of the trauma underlying their mental health problems.

Dr. Nutt said that in the United Kingdom, they haven’t seen adverse reactions in patients receiving psychedelic therapy, although sedatives such as benzodiazepines could be used to manage them. He added that at his center, two therapists are present at every treatment session, and all personnel are “trained medics or psychologists.”
 

Patient education

Preparing and educating patients about the therapy are critical, said Dr. Gründer, especially given the intense response psychedelic treatment often invokes.

Echoing Dr. Gründer, Dr. Tófoli said explaining the nature of psychedelic treatment to potential patients helps ease anxiety.

Dr. Griffiths noted that in the United States, study participants are not only educated about the potential effects of psychedelic agents but also undergo several hours of psychological preparation in advance of their first treatment session and are provided with psychological support after treatment.

There is also a strong emphasis on patient preparation and education in the United Kingdom, where patients meet with therapists before and after treatment. During these posttreatment debriefings, clinicians use the patients’ experience with psychedelics to help them gain insight into the underlying cause of their depression.

Dr. Schenberg noted that at his institution in São Paulo, there are online courses to teach clinicians about psychedelic therapy for psychiatric disorders. Next year, he added, a new training program in MDMA-assisted psychotherapy will begin.
 

Working out treatment protocols

Treatment protocols for psychedelics vary by agent and indication from country to country. For instance, Dr. Pani noted that current psychedelic research in Italy predominantly focuses more on microdosing, which involves administering 1% of the pharmacologically active dose to a maximum of 100 mcg, in contrast to low dosing or full dosing.

Therapeutic regimens in Brazil, said Dr. Schenberg, also differ by agent but share common elements. For instance, psychedelics are always administered in a research setting, and sessions include concomitant psychotherapy.

In Germany, investigators are working to determine optimal treatment regimen for psilocybin for resistant depression in a randomized three-arm study planned for 2021.

For Mexico’s Dr. Velásquez, treatment regimens are complex and varied. Either way, he said, patients always require long-term follow-up.

With ketamine therapy, Dr. Ferreri said his team administers the drug in 45- to 60-minute intravenous infusion sessions in a hospital room without light or sound stimulation. Regardless of the drug’s immediate effect, he said, the protocol is repeated within a 6-month period.

The question of the duration of treatment effect is important. Dr. Griffiths said research suggests that the positive effects of psilocybin are long lasting and that most individuals report positive changes in mood, attitude, and behavior that endure for months or even years after the session.

“Our research has shown that the benefits of these experiences can last as long as 14 months, often longer, and that many participants characterize their psilocybin experience as among the most profound and personally meaningful experiences of their lives,” said Dr. Griffiths.

Dr. Nutt agreed, noting that a single intense “trip” can improve mood for weeks, months, or even years. Nevertheless, he said, in his experience, approximately three-quarters of patients treated with psychedelics for major depression relapse within 3-9 months.

“Most get better,” he said, “but the majority of depression comes back over a period of months.”

Given the current illegal status of the drugs, he said it’s nearly impossible to provide patients with regular, subsequent treatment with psychedelics over time.

“My suspicion is that you might well have to dose four or five times over a couple of years to get people to escape from very severe depression,” said Dr. Nutt. “The longer they’ve been depressed, the harder it is for them to make a full recovery, because it’s more entrenched in the brain.”

All experts agree that exciting times are ahead for psychedelics as therapeutics for a wide range of psychiatric disorders.

“We can look forward to continued growth and expansion of this research,” said Dr. Griffiths, “including the refinement of protocols for a variety of therapeutic indications and to the development of a variety of new classic psychedelic compounds.”

A version of this article first appeared on Medscape.com.

In 1967, when the United Nations Convention on Drugs classified psychedelics as schedule I substances, it effectively ended research into these agents as potential therapeutics for psychiatric disorders.

eskymaks/iStock/Getty Images

Psychedelics induce altered states of perception. They bind to the 5-hydroxytryptamine 2A (5-HT2A) receptor and include psilocybin, which is derived from “magic mushrooms”; N,N-dimethyltryptamine (DMT), a component of ayahuasca and mescaline (peyote cactus); and the synthesized compound D-lysergic acid diethylamide (LSD). Other agents, such as ketamine and 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy, are sometimes considered psychedelics as well.

Before they were classified as schedule I agents, psychedelics had been shown to be particularly beneficial for patients with treatment-resistant conditions, including depression and posttraumatic stress disorder (PTSD), especially when administered in a supportive, therapeutic setting.

Now, after a hiatus of almost 50 years, there is renewed global interest in the scientific investigation of psychedelics. The attention was spurred in part by several exploratory studies of DMT in humans conducted in the 1990s by Rick Strassman, MD, and colleagues at the University of New Mexico, Albuquerque.

Around the same time, Franz X. Vollenweider, MD, and colleagues at the University of Zürich began researching psilocybin and its effects on human behavior. However, it was a 2006 study of psilocybin by a team of researchers at Johns Hopkins University, Baltimore, that is widely cited as a catalyst for the current renaissance in psychedelic research.

To provide a broad-based, international perspective on these agents, including their current legal status and indications, treatment regimens, safety, efficacy, and future considerations, this news organization interviewed nine expert researchers from around the globe.
 

Global legal status

In most, if not all, countries, it is still illegal to prescribe psychedelics in other than a research setting.

In the United States, classic psychedelics remain schedule I substances and therefore are unavailable for clinical use. They can be used in research, but only with approval from the Food and Drug Administration under licensure from the Drug Enforcement Administration.

France lists all synthetic hallucinogens and hallucinogenic mushrooms as narcotic. As a result, possession, use, transportation, and collection are subject to criminal sanctions.

In France, NMDA antagonists such as ketamine and nitrous oxide are regarded as psychedelic molecules and can be used off label for various conditions or as part of research protocols authorized by the French public health code.

Although psychedelics are illegal under Mexican law, they are commonly used in indigenous communities as part of traditional rituals.

“The line between traditional consumption and psychedelic tourism is very thin,” José J. Mendoza Velásquez, MD, professor in the department of mental health, National Autonomous University of Mexico, Mexico City, said in an interview.

Psychedelics also are illegal in the United Kingdom, although government agencies have recently allowed research groups to investigate them. Psychedelics cannot be prescribed in Germany, Spain, or Italy. However, investigators in these countries can request permission from regulatory agencies to conduct research.

Brazil allows psychedelic substances to be researched, particularly ayahuasca, which has long traditional and religious roots in the country.

However, as in other countries, none of the classic psychedelics is regulated for therapeutic use in Brazil. It is widely expected that the Brazilian government will approve MDMA sometime in 2024 for use in the treatment of PTSD.
 

Potential indications

Psychedelics are currently under investigation as potential treatments for major depression, treatment-resistant depression, PTSD, pain management, and anorexia, among other conditions.

In France, Florian Ferreri, MD, PhD, at Hospital Saint-Antoine, Paris, is researching ketamine for treatment of patients with suicidal crisis/ideation and treatment-resistant depression.

In the United Kingdom, David Nutt, FMedSci, Edmond J. Safra Professor of Neuropsychopharmacology at Imperial College London, and his team have conducted studies of the use of psychedelics in conjunction with psychological support for patients with treatment-resistant depression, and they are currently exploring their use in the treatment of anorexia and various pain syndromes.

In Germany, Gerhard Gründer, MD, professor of psychiatry at the Central Institute of Mental Health, in Mannheim, noted that a study of psilocybin for treatment-resistant depression will launch sometime in 2021. In Italy, current research is focusing on MDMA and ketamine in the laboratory environment and in animal models for treating depression and drug abuse.

Researcher Helen Dolengevich-Segal, MD, a psychiatrist at Hospital Universitario del Henares, Madrid, noted that although research on esketamine for the treatment of severe depressive disorder with suicidal thoughts is underway, there is very limited published research from that country into the use of classic psychedelics for various psychiatric disorders, given their current illegal status.

Mexico’s Dr. Velásquez noted that although he is prohibited from prescribing psychedelics, he does have patients who take the drugs to augment medical treatment. For instance, he said, his patients frequently use psilocybin to help with severe depression, pain, and insomnia.
 

Environment is key

Most researchers agree that for psychedelics to be safe and effective, patient education and administration in a controlled environment by experienced clinicians are key to successful treatment.

Roland R. Griffiths, PhD, director of the Center for Psychedelic and Consciousness Research at Johns Hopkins, said that ongoing U.S. psilocybin research – primarily in major depressive disorder and psychological distress associated with life-threatening illness, drug addiction, anorexia nervosa, obsessive-compulsive disorder, and headache – generally includes one or two treatment sessions, each of which lasts 6-8 hours.

Such sessions typically involve oral administration of a moderately high dose of a psychedelic under what he characterizes as “psychologically supported conditions.”

For Dr. Griffiths, there are serious potential risks associated with the use of psilocybin and other psychedelics outside such environments.

“When taken in uncontrolled conditions, classic psychedelics can produce confusion and disorientation resulting in behavior dangerous to the participant and others, including life-threatening risk,” he said.

Dr. Gründer agreed.

“At the moment, I cannot imagine that you would go to the pharmacy with a prescription for psilocybin and get yourself a pill and then take it in a quiet little room,” he said. Dr. Dolengevich-Segal and Dr. Velásquez echoed these sentiments, noting the optimal location for administration is one that is quiet and secure and where patients feel safe.

Luís Fernando Tófoli, MD, PhD, professor of medical psychology and psychiatry at the University of Campinas, and Eduardo Schenberg, PhD, founder and CEO of Instituto Phaneros in São Paulo, Brazil, said more research is needed to determine the optimal therapeutic environment for individual agents.

“Most studies have a low number of participants (around 20 or 30), especially in neuroimaging, with high unblinding rates,” Dr. Schenberg said. “Therefore, novel methodological approaches are also necessary, as these substances do not easily fit into the traditional pharmacology epistemic model.”
 

Risks, abuse potential

The abuse potential of psychedelics is an ongoing concern for the public, researchers, and regulators, but the consensus among nearly all of these experts is that when administered by medical professionals in controlled settings, these drugs are associated with extremely low risk.

It is recreational use that presents an abuse concern, said Dr. Ferreri, but with the low doses used in psychiatry, the risk is “very limited or even nonexistent.”

Dr. Nutt said the abuse potential of psychedelics is so low that they can be used to treat addiction.

“Functionally, psychedelics are antiaddictive,” Dr. Nutt said. “The fact is, if you take them repeatedly, you develop tolerance, and the effect disappears. You can’t overcome it. But everyone believes they’re addictive because they’re scheduled drugs.”

Dr. Velásquez is something of an outlier. He believes the abuse potential with psychedelics is poorly understood and that some patients may develop tolerance, which is a potential gateway to dependence.

“Such is the case with LSD,” he said, “where this substance also favors tolerance to other psychedelic drugs such as psilocybin.”

Dosing also seems to play a key role in mitigating potential abuse, said Luca Pani, MD, professor of pharmacology and psychiatry at the University of Modena, Italy. Dr. Pani explained that with low doses and microdoses of psychedelics, the potential for abuse is eliminated.

Dr. Nutt, Dr. Pani, and Dr. Ferreri also noted the importance of medical supervision. For instance, said Dr. Ferreri, when administering ketamine, his team closely monitors both mental and physical parameters – heart rate and blood pressure, in particular – because the drug can have hypertensive effects.

Dr. Schenberg noted that ibogaine, a naturally occurring psychedelic frequently used by traditional communities in Africa in rituals and for healing purposes, could cause potentially fatal arrhythmias, so it’s critical that the treatment is administered in a hospital setting that has a cardiac unit.

Dr. Pani said there is a need for more research, especially regarding the molecular mechanisms behind the behavioral effects of low-dose psychedelic therapy and the potential risks of multiple treatments with the drugs.

“Although extensive toxicology has been conducted on a single active dose of psilocybin, which has been proven to be safe, further research is required to understand better the possible health risks, especially in relation to cardiac and lung tissue,” he said.
 

Psychologically challenging

The experts note that given the relative lack of experience with psychedelic therapy, preparing patients for potential adverse effects is paramount. This is particularly relevant in the research setting and highlights the need for adequate patient screening and aftercare.

Dr. Gründer and Dr. Dolengevich-Segal emphasized the importance of having qualified personnel available in the event that patients experience adverse psychological events during treatment.

For Dr. Gründer, the potential for psilocybin to cause patients to lose control, experience psychotic symptoms, or become paranoid warrants considerable preparation by treating physicians.

Patients occasionally experience fear and anxiety during treatment, though it’s usually short-lived, said Dr. Griffiths. Nevertheless, these experiences may open the door to greater insight. “A number of people report that these psychologically challenging states are a valuable part of the overall experience,” he said.

The situation is similar in Spain, where Dr. Dolengevich-Segal noted that typical treatment regimens have a strong focus on the patient’s experience as a therapeutic tool. As in the United Kingdom and the United States, her team guides patients to what they call a “peak experience,” which allows them to gain a better understanding of the trauma underlying their mental health problems.

Dr. Nutt said that in the United Kingdom, they haven’t seen adverse reactions in patients receiving psychedelic therapy, although sedatives such as benzodiazepines could be used to manage them. He added that at his center, two therapists are present at every treatment session, and all personnel are “trained medics or psychologists.”
 

Patient education

Preparing and educating patients about the therapy are critical, said Dr. Gründer, especially given the intense response psychedelic treatment often invokes.

Echoing Dr. Gründer, Dr. Tófoli said explaining the nature of psychedelic treatment to potential patients helps ease anxiety.

Dr. Griffiths noted that in the United States, study participants are not only educated about the potential effects of psychedelic agents but also undergo several hours of psychological preparation in advance of their first treatment session and are provided with psychological support after treatment.

There is also a strong emphasis on patient preparation and education in the United Kingdom, where patients meet with therapists before and after treatment. During these posttreatment debriefings, clinicians use the patients’ experience with psychedelics to help them gain insight into the underlying cause of their depression.

Dr. Schenberg noted that at his institution in São Paulo, there are online courses to teach clinicians about psychedelic therapy for psychiatric disorders. Next year, he added, a new training program in MDMA-assisted psychotherapy will begin.
 

Working out treatment protocols

Treatment protocols for psychedelics vary by agent and indication from country to country. For instance, Dr. Pani noted that current psychedelic research in Italy predominantly focuses more on microdosing, which involves administering 1% of the pharmacologically active dose to a maximum of 100 mcg, in contrast to low dosing or full dosing.

Therapeutic regimens in Brazil, said Dr. Schenberg, also differ by agent but share common elements. For instance, psychedelics are always administered in a research setting, and sessions include concomitant psychotherapy.

In Germany, investigators are working to determine optimal treatment regimen for psilocybin for resistant depression in a randomized three-arm study planned for 2021.

For Mexico’s Dr. Velásquez, treatment regimens are complex and varied. Either way, he said, patients always require long-term follow-up.

With ketamine therapy, Dr. Ferreri said his team administers the drug in 45- to 60-minute intravenous infusion sessions in a hospital room without light or sound stimulation. Regardless of the drug’s immediate effect, he said, the protocol is repeated within a 6-month period.

The question of the duration of treatment effect is important. Dr. Griffiths said research suggests that the positive effects of psilocybin are long lasting and that most individuals report positive changes in mood, attitude, and behavior that endure for months or even years after the session.

“Our research has shown that the benefits of these experiences can last as long as 14 months, often longer, and that many participants characterize their psilocybin experience as among the most profound and personally meaningful experiences of their lives,” said Dr. Griffiths.

Dr. Nutt agreed, noting that a single intense “trip” can improve mood for weeks, months, or even years. Nevertheless, he said, in his experience, approximately three-quarters of patients treated with psychedelics for major depression relapse within 3-9 months.

“Most get better,” he said, “but the majority of depression comes back over a period of months.”

Given the current illegal status of the drugs, he said it’s nearly impossible to provide patients with regular, subsequent treatment with psychedelics over time.

“My suspicion is that you might well have to dose four or five times over a couple of years to get people to escape from very severe depression,” said Dr. Nutt. “The longer they’ve been depressed, the harder it is for them to make a full recovery, because it’s more entrenched in the brain.”

All experts agree that exciting times are ahead for psychedelics as therapeutics for a wide range of psychiatric disorders.

“We can look forward to continued growth and expansion of this research,” said Dr. Griffiths, “including the refinement of protocols for a variety of therapeutic indications and to the development of a variety of new classic psychedelic compounds.”

A version of this article first appeared on Medscape.com.