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The popularity of electronic cigarettes (E-cigs) and “vapes” has grown dramatically, spawning a new industry of electronic nicotine delivery systems (ENDS). With the increasing use of E-cigs not only for smoking cessation, but also as a primary nicotine source, it is important for mental health professionals to be prepared to discuss use of these devices with patients. In this article, we will describe:
- the composition of E-cigs and their current use
- evidence for their use for smoking cessation
- adverse health effects
- recommendations of major regulatory agencies.
Finally, we will provide recommendations for E-cig use in clinical populations.
What is an electronic nicotine delivery system?
ENDS produce an aerosol with or without nicotine that is inhaled and is thought to mimic the use of combustible cigarettes. ENDS evolved from basic E-cigs into a less “cigarette-like” and more customizable product (Figure 1). ENDS include a range of designs and go by various names, including “personal vaporizers,” “e-cigars,” and “e-hookahs” (in this article, we will use the term “ENDS” to refer to these devices).
The general design of ENDS is a plastic tubing system that contains a mouthpiece, battery, electronic heating element (“vaporizer”), and a cartridge with liquid solvent with or without nicotine or flavoring (Figure 2). One draw on the mouthpiece or press of a button activates the device, heats the solution, and delivers a vapor in a similar manner to taking a puff of a cigarette. Although studies have shown that ENDS result in significant increases in plasma nicotine concentrations in 5 minutes,1 the plasma nicotine levels obtained with the first-generation “cigarette-like” ENDS are much lower than those caused by inhaling tobacco smoke.2 Over time nicotine delivery capability has improved as ENDS have evolved such that the rate of nicotine delivery and peak concentration obtained with newer models more closely mirror tobacco cigarettes.3 Whether the rapid delivery of larger amounts of nicotine helps or hinders one’s efforts to break nicotine addiction remains to be determined because of the reinforcing properties of the drug.
The liquid in the E-cig cartridge typically contains not only nicotine but a number of chemical compounds with potentially deleterious or unknown health risks. The 3 main ingredients include:
- a solvent of glycerin and/or propylene glycol
- nicotine in various concentrations
- flavorings.
The glycerin or propylene glycol forms the basis for the aerosol. Nicotine concentrations vary from 0 (denicotinized) to 35 mcg per puff.4 A study reported 7,700 unique flavors available for vaping liquid.5 The liquid also contains impurities, such as anabasine, which has effects on the α-7 nicotinic acetylcholine receptor and its principal use is as an insecticide and β-nicotyrine, which inhibits cytochrome P450 2A.
Epidemiology and end-user perspectives
In 2014, 12.4% of U.S. adults classified themselves as “ever users” of ENDS (used at least once) and 3.7% of adults classified themselves as current users, according to the National Health Interview Study.6 Importantly, among E-cig users who had not used combustible cigarettes, young adults (age 18 to 24) were more likely to have tried ENDS than older adults. ENDS are becoming more popular across the globe. A study in the European Union found that ever users of ENDS most commonly were current cigarette smokers (31%) followed by former (10.8%) and never smokers (2.3%).7
ENDS use is relevant for mental health professionals because of the high rate of comorbid tobacco use disorder in individuals with psychiatric conditions. For example, 2 U.S. population surveys8,9 revealed those with mental health conditions were 1.5 to 2 times more likely to have tried ENDS and 2 to 3 times more likely to be current users. Those with psychiatric illness reported similar reasons for ENDS use as other individuals, including “just because,” use as a smoking cessation aid, ease of use, and perceived safety vs combustible cigarettes.
A recent review that included 9 studies focusing on ENDS use in those with mental illness reported mixed findings on the utility of these devices to reduce or stop use of combustible cigarettes.10 Additionally, it is important to monitor the use of cigarettes and ENDS in patients with psychiatric illness because the byproducts of tobacco smoke can affect the metabolism of some psychotropic medications.11 Although reduced use of combustible cigarettes could lead to lower dosing of some psychotropics, an unreported decrease in combustible cigarette use could lead to supratherapeutic drug levels. There are no data on the effect of ENDS on the metabolism of psychotropics.
ENDS are increasingly popular among adolescents. In 2015, there were an estimated 4.6 million current tobacco users among middle/high school youths in the United States and 3 million current ENDS users, according to the National Youth Tobacco Surveys.12 The shift from combustible cigarettes to ENDS is notable, with an increase in the percentage of current E-cig users and a decrease in the percentage of exclusive combustible cigarette users. In addition, there has been no change in the prevalence of lifetime tobacco users.12 This is a global issue, as reports of ever use of ENDS by adolescents range from 6.5% to 31% in the United States, 14.6% in Canada, and 4.7% to 38.5% in Europe.13 Based on these trends, the U.S. Surgeon General released a statement warning against the use of ENDS in youth because of the lack of safety data and strong association with use of tobacco products.14
There are a number of possible reasons for the increasing popularity of ENDS, including the product’s novelty, lack of regulations regarding their sale, availability of flavorings, and the perception that ENDS are safe alternatives to cigarettes. E-cig–using youths have described ENDS as “not at all harmful” and “not at all addictive” and believe that ENDS with flavoring are less harmful than those without.15 Although studies in adults show some users reporting that ENDS are less satisfying, they are seen as useful in decreasing craving and a safer alternative to cigarettes.16,17
Are ENDS effective for smoking cessation?
The evidence for ENDS as aids to smoking cessation remains murky (Table 118-22). There is a paucity of randomized controlled clinical trials (RCTs) investigating ENDS for smoking cessation or reduction, and it is difficult to quantify the amount of nicotine used in ENDS because of the variety of delivery systems and cartridges. In a recent Cochrane review, those using ENDS to quit smoking were more likely to be abstinent from combustible cigarettes at 6 months vs those using nicotine-free ENDS (relative risk = 2.29; 95% CI, 1.05 to 4.96), but there was no significant difference in quit rates compared with nicotine patches.23 However, the confidence in this finding was rated as low because of the limited number of RCTs. Of note, the authors found 15 ongoing RCTs at the time of publication that might be eligible for later evaluation.
Non-RCTs reveal mixed data. Positive results include 1 study with an odds ratio of 6.07 to quit for intensive ENDS users vs non-users,24 and another with dual users of combustible and electronic cigarettes having a 46% quit rate at 1 year.25 Additionally, in a pilot study providing ENDS to 14 patients with schizophrenia who had no previous desire to quit smoking, authors noted a reduction in the number of cigarettes smoked per day by 50% in one-half of participants and abstinence in 14% of participants at 52 weeks.26 Studies with neutral or negative results include those showing ENDS users to be current combustible tobacco smokers, and use of ENDS not predicting smoking cessation.4,27 Data also are mixed regarding the use of ENDS as a harm reduction strategy. One study found that ENDS decreased cigarette consumption, but did not increase the likelihood of quitting,28 while another reported that daily use of ENDS increased the odds of reducing smoking by as much as 2.5 times compared with non-use of such aids.29 In a 24-month prospective cohort study following tobacco users, there was no difference in the number of cigarettes smoked per day in those who started the trial as users of combustible cigarettes alone vs combustible cigarettes plus ENDS users.30 Interestingly, those who started the study as combustible cigarette users and switched to ENDS and those who had continued dual use throughout the 24 months smoked fewer combustible cigarettes per day than those who never tried ENDS or quit during the study period.
Health effects
To better understand the adverse health effects of ENDS, one must consider potential short- and long-term consequences (Table 2). In the short-term, ENDS have been found to increase markers of inflammation and oxidative stress acutely as evidenced by in vivo laboratory studies.31,32 ENDS also have been linked to upper respiratory irritation, in part, because of the transformation of glycerin in the nicotine cartridge to acrolein upon combustion.33 Even 5 minutes of ad lib E-cig use has been found to significantly increase airflow resistance during pulmonary function tests34—changes that have been shown to precede more persistent alterations in peak expiratory flow, such as those seen in chronic obstructive pulmonary disease. The more common patient-reported side effects include:
- daytime cough (27%)
- phlegm production (25%)
- headache (21%)
- dry mouth/throat (20%)
- vertigo, headache, or nausea (9%).35,36
A RCT investigating efficacy of E-cigs vs nicotine patches vs denicotinized E-cigs found no difference among the groups in the number of reported adverse events.18 Interestingly, another RCT found a decrease in adverse events, such as dry cough, mouth irritation, throat irritation, shortness of breath, and headache, compared with baseline in combustible cigarette smokers who used regular or denicotinized E-cigs.19
Although no studies have directly investigated long-term health consequences of ENDS because of their relative novelty, one can extrapolate potential harmful long-term effects based on knowledge of the products’ chemical constituents. For example, propylene glycol can degrade into propylene oxide, a class 2B carcinogen.37 Other potential carcinogens in the aerosol include formaldehyde and acetaldehyde. On a broader scale, many of the particulates have been shown to cause systemic inflammation, which is thought to increase cardiovascular and respiratory disease and death.38 Flavorings in ENDS include a variety of components including, but not limited to, aldehydes, which are irritants, and other additives that have been associated with respiratory disease.39
Second-hand exposure. There are no long-term studies of second-hand vapor exposure, but similar to long-term health on primary users, one can glean some observations from the literature. It is promising that compared with cigarettes, ENDS lack sidestream smoke and the vapor has not been found to contain carbon monoxide.40 Some research has demonstrated that the size and spray of fine particles in the aerosol is as large or larger than combustible cigarettes.41 Formaldehyde, acetaldehyde, isoprene, and acetic acid have been found in ENDS vapor.40 Interestingly, a simulated café study found elevated nicotine, glycerine, hydrocarbon, and other materials classified as carcinogens in the air.42
Although it is popularly thought that ENDS are less toxic than tobacco cigarettes, there is not enough evidence to estimate precisely as to how much less toxic or the consequences of use. ENDS are increasingly popular and are being used by never smokers who should be educated on the potential harm that ENDS pose.
Recommendations from agencies and medical organizations
The World Health Organization (WHO) recommended prohibiting the use of ENDS in indoor spaces to minimize potential health risks to users and non-users. The WHO also aims to prevent dissemination of unproven health claims, including claims that ENDS are effective—or not—or that the devices are innocuous.36 In the United States, the FDA has stated that ENDS are not recommended for safe quitting (2009). In August 2016, the FDA introduced regulations banning the sale of ENDS to individuals age <18 and required manufacturers to submit documents detailing all ingredients for review and possible approval.
The American Lung Association has stated its concerns about the use of ENDS but has not made any direct recommendations. The American Heart Association reports a potential negative public health impact and provides clinical guideline recommendations.43 Prominent psychiatric organizations such as the American Psychiatric Association, American Academy of Addiction Psychiatry (AAAP), the Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute of Drug Abuse do not have official statements supporting or rejecting the use of ENDS. However, they do note the potential harm and lack of substantial evidence for efficacy of ENDS as a smoking cessation tool, and the AAAP and SAMHSA state that they will work with regulatory agencies to reduce the use of toxic products with addictive potential including ENDS.44-46
Clinical recommendations
We do not recommend ENDS as a first-line treatment for smoking cessation because there is no evidence they are superior to the FDA-approved nicotine replacement therapies (NRTs), the paucity of research into the potential short- and long-term health risks of ENDS, and the fact that these products are not regulated for use as smoking cessation aids. It is, however, advisable to discuss ENDS use with patients by:
- asking if they are using the products
- assessing whether the user also is a smoker
- advising the patient to quit.
It also is important to assess the patient’s knowledge and attitudes regarding ENDS use and provide education about the products. Some patients firmly believe that ENDS are the lesser of 2 evils, and they are decreasing the harms of smoking by using these devices. While the debate over a potential harm reduction strategy unfolds,47 we think that because of the state of the evidence it is prudent to adopt a more precautionary stance and recommend that patients work toward abstinence from nicotine in any form.
For dual tobacco/ENDS users and for patients using ENDS who want to quit smoking, we recommend treatment with an approved pharmacotherapy (ie, NRTs, bupropion, and varenicline) combined with counseling. A 2013 Cochrane Review found that all pharamacotherapy options are more effective than placebo, and combination NRT and varenicline are superior to single NRT or bupropion (Box).23,48
1. Hajek P, Goniewicz ML, Phillips A, et al. Nicotine intake from electronic cigarettes on initial use and after 4 weeks of regular use. Nicotine Tob Res. 2015;17(2):175-179.
2. Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Saf. 2014;5(2):67-86.
3. St Helen G, Havel C, Dempsey DA, et al. Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes. Addiction. 2016;111(3):535-544.
4. Grana R, Benowitz N, Glantz SA. E-cigarettes: a scientific review. Circulation. 2014;129(19):1972-1986.
5. Zhu SH, Sun JY, Bonnevie E, et al. Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation. Tob Control. 2014;23(suppl 3):iii3-iii9. doi: 10.1136/tobaccocontrol-2014-051670.
6. Schoenborn CA, Gindi RM. Electronic cigarette use among adults: United States, 2014. NCHS Data Brief. 2015;(217):1-8.
7. Farsalinos KE, Poulas K, Voudris V, et al. Electronic cigarette use in the European Union: analysis of a representative sample of 27 460 Europeans from 28 countries. Addiction. 2016;111(11):2032-2040.
8. Cummins SE, Zhu SH, Tedeschi GJ, et al. Use of e-cigarettes by individuals with mental health conditions. Tob Control. 2015;23(suppl 3):iii48-iii53. doi: 10.1136/tobaccocontrol-2013-051511.
9. Spears CA, Jones DM, Weaver SR, et al. Use of electronic nicotine delivery systems among adults with mental health conditions, 2015. Int J Environ Res Public Heal. 2017;14(1):10.
10. Hefner K, Valentine G, Sofuoglu M. Electronic cigarettes and mental illness: reviewing the evidence for help and harm among those with psychiatric and substance use disorders [published online February 2, 2017]. Am J Addict. doi: 10.1111/ajad.12504.
11. Anthenelli R. How—and why—to help psychiatric patients stop smoking. Current Psychiatry. 2005;4(1):77-87.
12. Singh T, Arrazola RA, Corey CG, et al. Tobacco use among middle and high school students—United States, 2011-2015. MMWR Morb Mortal Wkly Rep. 2016;65(14):361-367.
13. Greenhill R, Dawkins L, Notley C, et al. Adolescent awareness and use of electronic cigarettes: a review of emerging trends and findings. J Adolesc Heal. 2016;59(6):612-619.
14. U.S. Department of Health and Human Services. E-cigarette use among youth and young adults: a report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2016.
15. Cooper M, Harrell MB, Pérez A, et al. Flavorings and perceived harm and addictiveness of e-cigarettes among youth. Tob Regul Sci. 2016;2(3):278-289.
16. Kim H, Davis AH, Dohack JL, et al. E-cigarettes use behavior and experience of adults: qualitative research findings to inform e-cigarette use measure development. Nicotine Tob Res. 2017;19(2):190-196.
17. Czoli CD, Fong GT, Mays D, et al. How do consumers perceive differences in risk across nicotine products? A review of relative risk perceptions across smokeless tobacco, e-cigarettes, nicotine replacement therapy and combustible cigarettes. Tob Control. 2017;26(e1):e49-e58.
18. Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013;382(9905):1629-1637.
19. Caponnetto P, Campagna D, Cibella F, et al. EffiCiency and safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One. 2013;8(6):e66317. doi: 10.1371/journal.pone.0066317.
20. Adriaens K, Van Gucht D, Declerck P, et al. Effectiveness of the electronic cigarette: an eight-week Flemish study with six-month follow-up on smoking reduction, craving and experienced benefits and complaints. Int J Environ Res Public Health. 2014;11(11):11220-11248.
21. Tseng TY, Ostroff JS, Campo A, et al. A randomized trial comparing the effect of nicotine versus placebo electronic cigarettes on smoking reduction among young adult smokers. Nicotine Tob Res. 2016;18(10):1937-1943.
22. Meier E, Wahlquist AE, Heckman BW, et al. A pilot randomized crossover trial of electronic cigarette sampling among smokers. Nicotine Tob Res. 2017;19(2):176-182.
23. Hartmann-Boyce J, McRobbie H, Bullen C, et al. Electronic cigarettes for smoking cessation [published online September 14, 2016]. Cochrane Database Syst Rev. 2016;9:CD010216.
24. Biener L, Hargraves JL. A longitudinal study of electronic cigarette use among a population-based sample of adult smokers: association with smoking cessation and motivation to quit. Nicotine Tob Res. 2014;17(2):127-133.
25. Etter JF, Bullen C. A longitudinal study of electronic cigarette users. Addict Behav. 2014;39(2):491-494.
26. Caponnetto P, Auditore R, Russo C, et al. Impact of an electronic cigarette on smoking reduction and cessation in schizophrenic smokers: a prospective 12-month pilot study. Int J Environ Res Public Health. 2013;10(2):446-461.
27. Popova L, Ling PM. Alternative tobacco product use and smoking cessation: a national study. Am J Public Health. 2013;103(5):923-930.
28. Adkison SE, O’Connor RJ, Bansal-Travers M, et al. Electronic nicotine delivery systems: International Tobacco Control Four-Country Survey. Am J Prev Med. 2013;44(3):207-215.
29. Brose LS, Hitchman SC, Brown J, et al. Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up. Addiction. 2015;110(7):1160-1168.
30. Manzoli L, Flacco ME, Ferrante M, et al; ISLESE Working Group. Cohort study of electronic cigarette use: effectiveness and safety at 24 months [published online June 6, 2016]. Tob Control. doi: 10.1136/tobaccocontrol-2015-052822.
31. Lerner CA, Sundar IK, Yao H, et al. Vapors produced by electronic cigarettes and E-juices with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and in mouse lung. PLoS One. 2015;10(2):e0116732. doi: 10.1371/journal.pone.0116732.
32. Sussan TE, Gajghate S, Thimmulappa RK, et al. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model. PLoS One. 2015;10(2):e0116861. doi: 10.1371/journal.pone.0116861.
33. US Environmental Protection Agency. Acrolein. https://www.epa.gov/sites/production/files/2016-08/documents/acrolein.pdf. Updated September 2009. Accessed April 7, 2017.
34. Vardavas CI, Anagnostopoulos N, Kougias M, et al. Short-term pulmonary effects of using an electronic cigarette: impact on respiratory flow resistance, impedance, and exhaled nitric oxide. Chest. 2012;141(6):1400-1406.
35. Etter JF. Electronic cigarettes: a survey of users. BMC Public Health. 2010;10:231.
36. Goniewicz ML, Lingas EO, Hajek P. Patterns of electronic cigarette use and user beliefs about their safety and benefits: an internet survey. Drug Alcohol Rev. 2013;32(2):133-140.
37. Laino T, Tuma C, Moor P, et al. Mechanisms of propylene glycol and triacetin pyrolysis. J Phys Chem A. 2012;116(18):4602-4609.
38. Brook RD, Rajagopalan S, Pope CA 3rd, et al; American Heart Association Council on Epidemiology and Prevention; Council on the Kidney in Cardiovascular Disease; Council on Nutrition, Physical Activity and Metabolism. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation. 2010;121(21):2331-2378.
39. Barrington-Trimis JL, Samet JM, McConnell R. Flavorings in electronic cigarettes: an unrecognized respiratory health hazard? JAMA. 2014;312(23):2493-2494.
40. Schripp T, Markewitz D, Uhde E, et al. Does e-cigarette consumption cause passive vaping? Indoor Air. 2013;23(1):25-31.
41. Fuoco FC, Buonanno G, Stabile L, et al. Influential parameters on particle concentration and size distribution in the mainstream of e-cigarettes. Environ Pollut. 2014;184:523-529.
42. Schober W, Szendrei K, Matzen W, et al. Use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers. Int J Hyg Environ Health. 2014;217(6):628-637.
43. Bhatnagar A, Whitsel L, Ribisl K, et al; American Heart Association Advocacy Coordinating Committee; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Quality of Care and Outcomes Research. Electronic cigarettes: a policy statement from the American Heart Association. Circulation. 2014;130(16):1418-1436.
44. E-cigarettes pose risks. SAMHSA News. https://www.samhsa.gov/samhsaNewsLetter/Volume_22_Number_3/e_cigarettes. Published 2014. Accessed April 7, 2017.
45. National Institute on Drug Abuse. Electronic cigarettes (e-cigarettes). https://www.drugabuse.gov/publications/drugfacts/electronic-cigarettes-e-cigarettes. Revised May 2016. Accessed April 7, 2017.
46. American Academy of Addiction Psychiatry. Nicotine dependence. East Providence, RI: American Academy of Addition Psychiatry; 2015.
47. Green SH, Bayer R, Fairchild AL. Evidence, policy, and e-cigarettes — will England reframe the debate. N Engl J Med. 2016;374(14):1301-1303.
48. Cahill K, Stevens S, Lancaster T. Pharmacological treatments for smoking cessation. JAMA. 2014;311(2):193-194.
The popularity of electronic cigarettes (E-cigs) and “vapes” has grown dramatically, spawning a new industry of electronic nicotine delivery systems (ENDS). With the increasing use of E-cigs not only for smoking cessation, but also as a primary nicotine source, it is important for mental health professionals to be prepared to discuss use of these devices with patients. In this article, we will describe:
- the composition of E-cigs and their current use
- evidence for their use for smoking cessation
- adverse health effects
- recommendations of major regulatory agencies.
Finally, we will provide recommendations for E-cig use in clinical populations.
What is an electronic nicotine delivery system?
ENDS produce an aerosol with or without nicotine that is inhaled and is thought to mimic the use of combustible cigarettes. ENDS evolved from basic E-cigs into a less “cigarette-like” and more customizable product (Figure 1). ENDS include a range of designs and go by various names, including “personal vaporizers,” “e-cigars,” and “e-hookahs” (in this article, we will use the term “ENDS” to refer to these devices).
The general design of ENDS is a plastic tubing system that contains a mouthpiece, battery, electronic heating element (“vaporizer”), and a cartridge with liquid solvent with or without nicotine or flavoring (Figure 2). One draw on the mouthpiece or press of a button activates the device, heats the solution, and delivers a vapor in a similar manner to taking a puff of a cigarette. Although studies have shown that ENDS result in significant increases in plasma nicotine concentrations in 5 minutes,1 the plasma nicotine levels obtained with the first-generation “cigarette-like” ENDS are much lower than those caused by inhaling tobacco smoke.2 Over time nicotine delivery capability has improved as ENDS have evolved such that the rate of nicotine delivery and peak concentration obtained with newer models more closely mirror tobacco cigarettes.3 Whether the rapid delivery of larger amounts of nicotine helps or hinders one’s efforts to break nicotine addiction remains to be determined because of the reinforcing properties of the drug.
The liquid in the E-cig cartridge typically contains not only nicotine but a number of chemical compounds with potentially deleterious or unknown health risks. The 3 main ingredients include:
- a solvent of glycerin and/or propylene glycol
- nicotine in various concentrations
- flavorings.
The glycerin or propylene glycol forms the basis for the aerosol. Nicotine concentrations vary from 0 (denicotinized) to 35 mcg per puff.4 A study reported 7,700 unique flavors available for vaping liquid.5 The liquid also contains impurities, such as anabasine, which has effects on the α-7 nicotinic acetylcholine receptor and its principal use is as an insecticide and β-nicotyrine, which inhibits cytochrome P450 2A.
Epidemiology and end-user perspectives
In 2014, 12.4% of U.S. adults classified themselves as “ever users” of ENDS (used at least once) and 3.7% of adults classified themselves as current users, according to the National Health Interview Study.6 Importantly, among E-cig users who had not used combustible cigarettes, young adults (age 18 to 24) were more likely to have tried ENDS than older adults. ENDS are becoming more popular across the globe. A study in the European Union found that ever users of ENDS most commonly were current cigarette smokers (31%) followed by former (10.8%) and never smokers (2.3%).7
ENDS use is relevant for mental health professionals because of the high rate of comorbid tobacco use disorder in individuals with psychiatric conditions. For example, 2 U.S. population surveys8,9 revealed those with mental health conditions were 1.5 to 2 times more likely to have tried ENDS and 2 to 3 times more likely to be current users. Those with psychiatric illness reported similar reasons for ENDS use as other individuals, including “just because,” use as a smoking cessation aid, ease of use, and perceived safety vs combustible cigarettes.
A recent review that included 9 studies focusing on ENDS use in those with mental illness reported mixed findings on the utility of these devices to reduce or stop use of combustible cigarettes.10 Additionally, it is important to monitor the use of cigarettes and ENDS in patients with psychiatric illness because the byproducts of tobacco smoke can affect the metabolism of some psychotropic medications.11 Although reduced use of combustible cigarettes could lead to lower dosing of some psychotropics, an unreported decrease in combustible cigarette use could lead to supratherapeutic drug levels. There are no data on the effect of ENDS on the metabolism of psychotropics.
ENDS are increasingly popular among adolescents. In 2015, there were an estimated 4.6 million current tobacco users among middle/high school youths in the United States and 3 million current ENDS users, according to the National Youth Tobacco Surveys.12 The shift from combustible cigarettes to ENDS is notable, with an increase in the percentage of current E-cig users and a decrease in the percentage of exclusive combustible cigarette users. In addition, there has been no change in the prevalence of lifetime tobacco users.12 This is a global issue, as reports of ever use of ENDS by adolescents range from 6.5% to 31% in the United States, 14.6% in Canada, and 4.7% to 38.5% in Europe.13 Based on these trends, the U.S. Surgeon General released a statement warning against the use of ENDS in youth because of the lack of safety data and strong association with use of tobacco products.14
There are a number of possible reasons for the increasing popularity of ENDS, including the product’s novelty, lack of regulations regarding their sale, availability of flavorings, and the perception that ENDS are safe alternatives to cigarettes. E-cig–using youths have described ENDS as “not at all harmful” and “not at all addictive” and believe that ENDS with flavoring are less harmful than those without.15 Although studies in adults show some users reporting that ENDS are less satisfying, they are seen as useful in decreasing craving and a safer alternative to cigarettes.16,17
Are ENDS effective for smoking cessation?
The evidence for ENDS as aids to smoking cessation remains murky (Table 118-22). There is a paucity of randomized controlled clinical trials (RCTs) investigating ENDS for smoking cessation or reduction, and it is difficult to quantify the amount of nicotine used in ENDS because of the variety of delivery systems and cartridges. In a recent Cochrane review, those using ENDS to quit smoking were more likely to be abstinent from combustible cigarettes at 6 months vs those using nicotine-free ENDS (relative risk = 2.29; 95% CI, 1.05 to 4.96), but there was no significant difference in quit rates compared with nicotine patches.23 However, the confidence in this finding was rated as low because of the limited number of RCTs. Of note, the authors found 15 ongoing RCTs at the time of publication that might be eligible for later evaluation.
Non-RCTs reveal mixed data. Positive results include 1 study with an odds ratio of 6.07 to quit for intensive ENDS users vs non-users,24 and another with dual users of combustible and electronic cigarettes having a 46% quit rate at 1 year.25 Additionally, in a pilot study providing ENDS to 14 patients with schizophrenia who had no previous desire to quit smoking, authors noted a reduction in the number of cigarettes smoked per day by 50% in one-half of participants and abstinence in 14% of participants at 52 weeks.26 Studies with neutral or negative results include those showing ENDS users to be current combustible tobacco smokers, and use of ENDS not predicting smoking cessation.4,27 Data also are mixed regarding the use of ENDS as a harm reduction strategy. One study found that ENDS decreased cigarette consumption, but did not increase the likelihood of quitting,28 while another reported that daily use of ENDS increased the odds of reducing smoking by as much as 2.5 times compared with non-use of such aids.29 In a 24-month prospective cohort study following tobacco users, there was no difference in the number of cigarettes smoked per day in those who started the trial as users of combustible cigarettes alone vs combustible cigarettes plus ENDS users.30 Interestingly, those who started the study as combustible cigarette users and switched to ENDS and those who had continued dual use throughout the 24 months smoked fewer combustible cigarettes per day than those who never tried ENDS or quit during the study period.
Health effects
To better understand the adverse health effects of ENDS, one must consider potential short- and long-term consequences (Table 2). In the short-term, ENDS have been found to increase markers of inflammation and oxidative stress acutely as evidenced by in vivo laboratory studies.31,32 ENDS also have been linked to upper respiratory irritation, in part, because of the transformation of glycerin in the nicotine cartridge to acrolein upon combustion.33 Even 5 minutes of ad lib E-cig use has been found to significantly increase airflow resistance during pulmonary function tests34—changes that have been shown to precede more persistent alterations in peak expiratory flow, such as those seen in chronic obstructive pulmonary disease. The more common patient-reported side effects include:
- daytime cough (27%)
- phlegm production (25%)
- headache (21%)
- dry mouth/throat (20%)
- vertigo, headache, or nausea (9%).35,36
A RCT investigating efficacy of E-cigs vs nicotine patches vs denicotinized E-cigs found no difference among the groups in the number of reported adverse events.18 Interestingly, another RCT found a decrease in adverse events, such as dry cough, mouth irritation, throat irritation, shortness of breath, and headache, compared with baseline in combustible cigarette smokers who used regular or denicotinized E-cigs.19
Although no studies have directly investigated long-term health consequences of ENDS because of their relative novelty, one can extrapolate potential harmful long-term effects based on knowledge of the products’ chemical constituents. For example, propylene glycol can degrade into propylene oxide, a class 2B carcinogen.37 Other potential carcinogens in the aerosol include formaldehyde and acetaldehyde. On a broader scale, many of the particulates have been shown to cause systemic inflammation, which is thought to increase cardiovascular and respiratory disease and death.38 Flavorings in ENDS include a variety of components including, but not limited to, aldehydes, which are irritants, and other additives that have been associated with respiratory disease.39
Second-hand exposure. There are no long-term studies of second-hand vapor exposure, but similar to long-term health on primary users, one can glean some observations from the literature. It is promising that compared with cigarettes, ENDS lack sidestream smoke and the vapor has not been found to contain carbon monoxide.40 Some research has demonstrated that the size and spray of fine particles in the aerosol is as large or larger than combustible cigarettes.41 Formaldehyde, acetaldehyde, isoprene, and acetic acid have been found in ENDS vapor.40 Interestingly, a simulated café study found elevated nicotine, glycerine, hydrocarbon, and other materials classified as carcinogens in the air.42
Although it is popularly thought that ENDS are less toxic than tobacco cigarettes, there is not enough evidence to estimate precisely as to how much less toxic or the consequences of use. ENDS are increasingly popular and are being used by never smokers who should be educated on the potential harm that ENDS pose.
Recommendations from agencies and medical organizations
The World Health Organization (WHO) recommended prohibiting the use of ENDS in indoor spaces to minimize potential health risks to users and non-users. The WHO also aims to prevent dissemination of unproven health claims, including claims that ENDS are effective—or not—or that the devices are innocuous.36 In the United States, the FDA has stated that ENDS are not recommended for safe quitting (2009). In August 2016, the FDA introduced regulations banning the sale of ENDS to individuals age <18 and required manufacturers to submit documents detailing all ingredients for review and possible approval.
The American Lung Association has stated its concerns about the use of ENDS but has not made any direct recommendations. The American Heart Association reports a potential negative public health impact and provides clinical guideline recommendations.43 Prominent psychiatric organizations such as the American Psychiatric Association, American Academy of Addiction Psychiatry (AAAP), the Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute of Drug Abuse do not have official statements supporting or rejecting the use of ENDS. However, they do note the potential harm and lack of substantial evidence for efficacy of ENDS as a smoking cessation tool, and the AAAP and SAMHSA state that they will work with regulatory agencies to reduce the use of toxic products with addictive potential including ENDS.44-46
Clinical recommendations
We do not recommend ENDS as a first-line treatment for smoking cessation because there is no evidence they are superior to the FDA-approved nicotine replacement therapies (NRTs), the paucity of research into the potential short- and long-term health risks of ENDS, and the fact that these products are not regulated for use as smoking cessation aids. It is, however, advisable to discuss ENDS use with patients by:
- asking if they are using the products
- assessing whether the user also is a smoker
- advising the patient to quit.
It also is important to assess the patient’s knowledge and attitudes regarding ENDS use and provide education about the products. Some patients firmly believe that ENDS are the lesser of 2 evils, and they are decreasing the harms of smoking by using these devices. While the debate over a potential harm reduction strategy unfolds,47 we think that because of the state of the evidence it is prudent to adopt a more precautionary stance and recommend that patients work toward abstinence from nicotine in any form.
For dual tobacco/ENDS users and for patients using ENDS who want to quit smoking, we recommend treatment with an approved pharmacotherapy (ie, NRTs, bupropion, and varenicline) combined with counseling. A 2013 Cochrane Review found that all pharamacotherapy options are more effective than placebo, and combination NRT and varenicline are superior to single NRT or bupropion (Box).23,48
The popularity of electronic cigarettes (E-cigs) and “vapes” has grown dramatically, spawning a new industry of electronic nicotine delivery systems (ENDS). With the increasing use of E-cigs not only for smoking cessation, but also as a primary nicotine source, it is important for mental health professionals to be prepared to discuss use of these devices with patients. In this article, we will describe:
- the composition of E-cigs and their current use
- evidence for their use for smoking cessation
- adverse health effects
- recommendations of major regulatory agencies.
Finally, we will provide recommendations for E-cig use in clinical populations.
What is an electronic nicotine delivery system?
ENDS produce an aerosol with or without nicotine that is inhaled and is thought to mimic the use of combustible cigarettes. ENDS evolved from basic E-cigs into a less “cigarette-like” and more customizable product (Figure 1). ENDS include a range of designs and go by various names, including “personal vaporizers,” “e-cigars,” and “e-hookahs” (in this article, we will use the term “ENDS” to refer to these devices).
The general design of ENDS is a plastic tubing system that contains a mouthpiece, battery, electronic heating element (“vaporizer”), and a cartridge with liquid solvent with or without nicotine or flavoring (Figure 2). One draw on the mouthpiece or press of a button activates the device, heats the solution, and delivers a vapor in a similar manner to taking a puff of a cigarette. Although studies have shown that ENDS result in significant increases in plasma nicotine concentrations in 5 minutes,1 the plasma nicotine levels obtained with the first-generation “cigarette-like” ENDS are much lower than those caused by inhaling tobacco smoke.2 Over time nicotine delivery capability has improved as ENDS have evolved such that the rate of nicotine delivery and peak concentration obtained with newer models more closely mirror tobacco cigarettes.3 Whether the rapid delivery of larger amounts of nicotine helps or hinders one’s efforts to break nicotine addiction remains to be determined because of the reinforcing properties of the drug.
The liquid in the E-cig cartridge typically contains not only nicotine but a number of chemical compounds with potentially deleterious or unknown health risks. The 3 main ingredients include:
- a solvent of glycerin and/or propylene glycol
- nicotine in various concentrations
- flavorings.
The glycerin or propylene glycol forms the basis for the aerosol. Nicotine concentrations vary from 0 (denicotinized) to 35 mcg per puff.4 A study reported 7,700 unique flavors available for vaping liquid.5 The liquid also contains impurities, such as anabasine, which has effects on the α-7 nicotinic acetylcholine receptor and its principal use is as an insecticide and β-nicotyrine, which inhibits cytochrome P450 2A.
Epidemiology and end-user perspectives
In 2014, 12.4% of U.S. adults classified themselves as “ever users” of ENDS (used at least once) and 3.7% of adults classified themselves as current users, according to the National Health Interview Study.6 Importantly, among E-cig users who had not used combustible cigarettes, young adults (age 18 to 24) were more likely to have tried ENDS than older adults. ENDS are becoming more popular across the globe. A study in the European Union found that ever users of ENDS most commonly were current cigarette smokers (31%) followed by former (10.8%) and never smokers (2.3%).7
ENDS use is relevant for mental health professionals because of the high rate of comorbid tobacco use disorder in individuals with psychiatric conditions. For example, 2 U.S. population surveys8,9 revealed those with mental health conditions were 1.5 to 2 times more likely to have tried ENDS and 2 to 3 times more likely to be current users. Those with psychiatric illness reported similar reasons for ENDS use as other individuals, including “just because,” use as a smoking cessation aid, ease of use, and perceived safety vs combustible cigarettes.
A recent review that included 9 studies focusing on ENDS use in those with mental illness reported mixed findings on the utility of these devices to reduce or stop use of combustible cigarettes.10 Additionally, it is important to monitor the use of cigarettes and ENDS in patients with psychiatric illness because the byproducts of tobacco smoke can affect the metabolism of some psychotropic medications.11 Although reduced use of combustible cigarettes could lead to lower dosing of some psychotropics, an unreported decrease in combustible cigarette use could lead to supratherapeutic drug levels. There are no data on the effect of ENDS on the metabolism of psychotropics.
ENDS are increasingly popular among adolescents. In 2015, there were an estimated 4.6 million current tobacco users among middle/high school youths in the United States and 3 million current ENDS users, according to the National Youth Tobacco Surveys.12 The shift from combustible cigarettes to ENDS is notable, with an increase in the percentage of current E-cig users and a decrease in the percentage of exclusive combustible cigarette users. In addition, there has been no change in the prevalence of lifetime tobacco users.12 This is a global issue, as reports of ever use of ENDS by adolescents range from 6.5% to 31% in the United States, 14.6% in Canada, and 4.7% to 38.5% in Europe.13 Based on these trends, the U.S. Surgeon General released a statement warning against the use of ENDS in youth because of the lack of safety data and strong association with use of tobacco products.14
There are a number of possible reasons for the increasing popularity of ENDS, including the product’s novelty, lack of regulations regarding their sale, availability of flavorings, and the perception that ENDS are safe alternatives to cigarettes. E-cig–using youths have described ENDS as “not at all harmful” and “not at all addictive” and believe that ENDS with flavoring are less harmful than those without.15 Although studies in adults show some users reporting that ENDS are less satisfying, they are seen as useful in decreasing craving and a safer alternative to cigarettes.16,17
Are ENDS effective for smoking cessation?
The evidence for ENDS as aids to smoking cessation remains murky (Table 118-22). There is a paucity of randomized controlled clinical trials (RCTs) investigating ENDS for smoking cessation or reduction, and it is difficult to quantify the amount of nicotine used in ENDS because of the variety of delivery systems and cartridges. In a recent Cochrane review, those using ENDS to quit smoking were more likely to be abstinent from combustible cigarettes at 6 months vs those using nicotine-free ENDS (relative risk = 2.29; 95% CI, 1.05 to 4.96), but there was no significant difference in quit rates compared with nicotine patches.23 However, the confidence in this finding was rated as low because of the limited number of RCTs. Of note, the authors found 15 ongoing RCTs at the time of publication that might be eligible for later evaluation.
Non-RCTs reveal mixed data. Positive results include 1 study with an odds ratio of 6.07 to quit for intensive ENDS users vs non-users,24 and another with dual users of combustible and electronic cigarettes having a 46% quit rate at 1 year.25 Additionally, in a pilot study providing ENDS to 14 patients with schizophrenia who had no previous desire to quit smoking, authors noted a reduction in the number of cigarettes smoked per day by 50% in one-half of participants and abstinence in 14% of participants at 52 weeks.26 Studies with neutral or negative results include those showing ENDS users to be current combustible tobacco smokers, and use of ENDS not predicting smoking cessation.4,27 Data also are mixed regarding the use of ENDS as a harm reduction strategy. One study found that ENDS decreased cigarette consumption, but did not increase the likelihood of quitting,28 while another reported that daily use of ENDS increased the odds of reducing smoking by as much as 2.5 times compared with non-use of such aids.29 In a 24-month prospective cohort study following tobacco users, there was no difference in the number of cigarettes smoked per day in those who started the trial as users of combustible cigarettes alone vs combustible cigarettes plus ENDS users.30 Interestingly, those who started the study as combustible cigarette users and switched to ENDS and those who had continued dual use throughout the 24 months smoked fewer combustible cigarettes per day than those who never tried ENDS or quit during the study period.
Health effects
To better understand the adverse health effects of ENDS, one must consider potential short- and long-term consequences (Table 2). In the short-term, ENDS have been found to increase markers of inflammation and oxidative stress acutely as evidenced by in vivo laboratory studies.31,32 ENDS also have been linked to upper respiratory irritation, in part, because of the transformation of glycerin in the nicotine cartridge to acrolein upon combustion.33 Even 5 minutes of ad lib E-cig use has been found to significantly increase airflow resistance during pulmonary function tests34—changes that have been shown to precede more persistent alterations in peak expiratory flow, such as those seen in chronic obstructive pulmonary disease. The more common patient-reported side effects include:
- daytime cough (27%)
- phlegm production (25%)
- headache (21%)
- dry mouth/throat (20%)
- vertigo, headache, or nausea (9%).35,36
A RCT investigating efficacy of E-cigs vs nicotine patches vs denicotinized E-cigs found no difference among the groups in the number of reported adverse events.18 Interestingly, another RCT found a decrease in adverse events, such as dry cough, mouth irritation, throat irritation, shortness of breath, and headache, compared with baseline in combustible cigarette smokers who used regular or denicotinized E-cigs.19
Although no studies have directly investigated long-term health consequences of ENDS because of their relative novelty, one can extrapolate potential harmful long-term effects based on knowledge of the products’ chemical constituents. For example, propylene glycol can degrade into propylene oxide, a class 2B carcinogen.37 Other potential carcinogens in the aerosol include formaldehyde and acetaldehyde. On a broader scale, many of the particulates have been shown to cause systemic inflammation, which is thought to increase cardiovascular and respiratory disease and death.38 Flavorings in ENDS include a variety of components including, but not limited to, aldehydes, which are irritants, and other additives that have been associated with respiratory disease.39
Second-hand exposure. There are no long-term studies of second-hand vapor exposure, but similar to long-term health on primary users, one can glean some observations from the literature. It is promising that compared with cigarettes, ENDS lack sidestream smoke and the vapor has not been found to contain carbon monoxide.40 Some research has demonstrated that the size and spray of fine particles in the aerosol is as large or larger than combustible cigarettes.41 Formaldehyde, acetaldehyde, isoprene, and acetic acid have been found in ENDS vapor.40 Interestingly, a simulated café study found elevated nicotine, glycerine, hydrocarbon, and other materials classified as carcinogens in the air.42
Although it is popularly thought that ENDS are less toxic than tobacco cigarettes, there is not enough evidence to estimate precisely as to how much less toxic or the consequences of use. ENDS are increasingly popular and are being used by never smokers who should be educated on the potential harm that ENDS pose.
Recommendations from agencies and medical organizations
The World Health Organization (WHO) recommended prohibiting the use of ENDS in indoor spaces to minimize potential health risks to users and non-users. The WHO also aims to prevent dissemination of unproven health claims, including claims that ENDS are effective—or not—or that the devices are innocuous.36 In the United States, the FDA has stated that ENDS are not recommended for safe quitting (2009). In August 2016, the FDA introduced regulations banning the sale of ENDS to individuals age <18 and required manufacturers to submit documents detailing all ingredients for review and possible approval.
The American Lung Association has stated its concerns about the use of ENDS but has not made any direct recommendations. The American Heart Association reports a potential negative public health impact and provides clinical guideline recommendations.43 Prominent psychiatric organizations such as the American Psychiatric Association, American Academy of Addiction Psychiatry (AAAP), the Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute of Drug Abuse do not have official statements supporting or rejecting the use of ENDS. However, they do note the potential harm and lack of substantial evidence for efficacy of ENDS as a smoking cessation tool, and the AAAP and SAMHSA state that they will work with regulatory agencies to reduce the use of toxic products with addictive potential including ENDS.44-46
Clinical recommendations
We do not recommend ENDS as a first-line treatment for smoking cessation because there is no evidence they are superior to the FDA-approved nicotine replacement therapies (NRTs), the paucity of research into the potential short- and long-term health risks of ENDS, and the fact that these products are not regulated for use as smoking cessation aids. It is, however, advisable to discuss ENDS use with patients by:
- asking if they are using the products
- assessing whether the user also is a smoker
- advising the patient to quit.
It also is important to assess the patient’s knowledge and attitudes regarding ENDS use and provide education about the products. Some patients firmly believe that ENDS are the lesser of 2 evils, and they are decreasing the harms of smoking by using these devices. While the debate over a potential harm reduction strategy unfolds,47 we think that because of the state of the evidence it is prudent to adopt a more precautionary stance and recommend that patients work toward abstinence from nicotine in any form.
For dual tobacco/ENDS users and for patients using ENDS who want to quit smoking, we recommend treatment with an approved pharmacotherapy (ie, NRTs, bupropion, and varenicline) combined with counseling. A 2013 Cochrane Review found that all pharamacotherapy options are more effective than placebo, and combination NRT and varenicline are superior to single NRT or bupropion (Box).23,48
1. Hajek P, Goniewicz ML, Phillips A, et al. Nicotine intake from electronic cigarettes on initial use and after 4 weeks of regular use. Nicotine Tob Res. 2015;17(2):175-179.
2. Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Saf. 2014;5(2):67-86.
3. St Helen G, Havel C, Dempsey DA, et al. Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes. Addiction. 2016;111(3):535-544.
4. Grana R, Benowitz N, Glantz SA. E-cigarettes: a scientific review. Circulation. 2014;129(19):1972-1986.
5. Zhu SH, Sun JY, Bonnevie E, et al. Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation. Tob Control. 2014;23(suppl 3):iii3-iii9. doi: 10.1136/tobaccocontrol-2014-051670.
6. Schoenborn CA, Gindi RM. Electronic cigarette use among adults: United States, 2014. NCHS Data Brief. 2015;(217):1-8.
7. Farsalinos KE, Poulas K, Voudris V, et al. Electronic cigarette use in the European Union: analysis of a representative sample of 27 460 Europeans from 28 countries. Addiction. 2016;111(11):2032-2040.
8. Cummins SE, Zhu SH, Tedeschi GJ, et al. Use of e-cigarettes by individuals with mental health conditions. Tob Control. 2015;23(suppl 3):iii48-iii53. doi: 10.1136/tobaccocontrol-2013-051511.
9. Spears CA, Jones DM, Weaver SR, et al. Use of electronic nicotine delivery systems among adults with mental health conditions, 2015. Int J Environ Res Public Heal. 2017;14(1):10.
10. Hefner K, Valentine G, Sofuoglu M. Electronic cigarettes and mental illness: reviewing the evidence for help and harm among those with psychiatric and substance use disorders [published online February 2, 2017]. Am J Addict. doi: 10.1111/ajad.12504.
11. Anthenelli R. How—and why—to help psychiatric patients stop smoking. Current Psychiatry. 2005;4(1):77-87.
12. Singh T, Arrazola RA, Corey CG, et al. Tobacco use among middle and high school students—United States, 2011-2015. MMWR Morb Mortal Wkly Rep. 2016;65(14):361-367.
13. Greenhill R, Dawkins L, Notley C, et al. Adolescent awareness and use of electronic cigarettes: a review of emerging trends and findings. J Adolesc Heal. 2016;59(6):612-619.
14. U.S. Department of Health and Human Services. E-cigarette use among youth and young adults: a report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2016.
15. Cooper M, Harrell MB, Pérez A, et al. Flavorings and perceived harm and addictiveness of e-cigarettes among youth. Tob Regul Sci. 2016;2(3):278-289.
16. Kim H, Davis AH, Dohack JL, et al. E-cigarettes use behavior and experience of adults: qualitative research findings to inform e-cigarette use measure development. Nicotine Tob Res. 2017;19(2):190-196.
17. Czoli CD, Fong GT, Mays D, et al. How do consumers perceive differences in risk across nicotine products? A review of relative risk perceptions across smokeless tobacco, e-cigarettes, nicotine replacement therapy and combustible cigarettes. Tob Control. 2017;26(e1):e49-e58.
18. Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013;382(9905):1629-1637.
19. Caponnetto P, Campagna D, Cibella F, et al. EffiCiency and safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One. 2013;8(6):e66317. doi: 10.1371/journal.pone.0066317.
20. Adriaens K, Van Gucht D, Declerck P, et al. Effectiveness of the electronic cigarette: an eight-week Flemish study with six-month follow-up on smoking reduction, craving and experienced benefits and complaints. Int J Environ Res Public Health. 2014;11(11):11220-11248.
21. Tseng TY, Ostroff JS, Campo A, et al. A randomized trial comparing the effect of nicotine versus placebo electronic cigarettes on smoking reduction among young adult smokers. Nicotine Tob Res. 2016;18(10):1937-1943.
22. Meier E, Wahlquist AE, Heckman BW, et al. A pilot randomized crossover trial of electronic cigarette sampling among smokers. Nicotine Tob Res. 2017;19(2):176-182.
23. Hartmann-Boyce J, McRobbie H, Bullen C, et al. Electronic cigarettes for smoking cessation [published online September 14, 2016]. Cochrane Database Syst Rev. 2016;9:CD010216.
24. Biener L, Hargraves JL. A longitudinal study of electronic cigarette use among a population-based sample of adult smokers: association with smoking cessation and motivation to quit. Nicotine Tob Res. 2014;17(2):127-133.
25. Etter JF, Bullen C. A longitudinal study of electronic cigarette users. Addict Behav. 2014;39(2):491-494.
26. Caponnetto P, Auditore R, Russo C, et al. Impact of an electronic cigarette on smoking reduction and cessation in schizophrenic smokers: a prospective 12-month pilot study. Int J Environ Res Public Health. 2013;10(2):446-461.
27. Popova L, Ling PM. Alternative tobacco product use and smoking cessation: a national study. Am J Public Health. 2013;103(5):923-930.
28. Adkison SE, O’Connor RJ, Bansal-Travers M, et al. Electronic nicotine delivery systems: International Tobacco Control Four-Country Survey. Am J Prev Med. 2013;44(3):207-215.
29. Brose LS, Hitchman SC, Brown J, et al. Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up. Addiction. 2015;110(7):1160-1168.
30. Manzoli L, Flacco ME, Ferrante M, et al; ISLESE Working Group. Cohort study of electronic cigarette use: effectiveness and safety at 24 months [published online June 6, 2016]. Tob Control. doi: 10.1136/tobaccocontrol-2015-052822.
31. Lerner CA, Sundar IK, Yao H, et al. Vapors produced by electronic cigarettes and E-juices with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and in mouse lung. PLoS One. 2015;10(2):e0116732. doi: 10.1371/journal.pone.0116732.
32. Sussan TE, Gajghate S, Thimmulappa RK, et al. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model. PLoS One. 2015;10(2):e0116861. doi: 10.1371/journal.pone.0116861.
33. US Environmental Protection Agency. Acrolein. https://www.epa.gov/sites/production/files/2016-08/documents/acrolein.pdf. Updated September 2009. Accessed April 7, 2017.
34. Vardavas CI, Anagnostopoulos N, Kougias M, et al. Short-term pulmonary effects of using an electronic cigarette: impact on respiratory flow resistance, impedance, and exhaled nitric oxide. Chest. 2012;141(6):1400-1406.
35. Etter JF. Electronic cigarettes: a survey of users. BMC Public Health. 2010;10:231.
36. Goniewicz ML, Lingas EO, Hajek P. Patterns of electronic cigarette use and user beliefs about their safety and benefits: an internet survey. Drug Alcohol Rev. 2013;32(2):133-140.
37. Laino T, Tuma C, Moor P, et al. Mechanisms of propylene glycol and triacetin pyrolysis. J Phys Chem A. 2012;116(18):4602-4609.
38. Brook RD, Rajagopalan S, Pope CA 3rd, et al; American Heart Association Council on Epidemiology and Prevention; Council on the Kidney in Cardiovascular Disease; Council on Nutrition, Physical Activity and Metabolism. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation. 2010;121(21):2331-2378.
39. Barrington-Trimis JL, Samet JM, McConnell R. Flavorings in electronic cigarettes: an unrecognized respiratory health hazard? JAMA. 2014;312(23):2493-2494.
40. Schripp T, Markewitz D, Uhde E, et al. Does e-cigarette consumption cause passive vaping? Indoor Air. 2013;23(1):25-31.
41. Fuoco FC, Buonanno G, Stabile L, et al. Influential parameters on particle concentration and size distribution in the mainstream of e-cigarettes. Environ Pollut. 2014;184:523-529.
42. Schober W, Szendrei K, Matzen W, et al. Use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers. Int J Hyg Environ Health. 2014;217(6):628-637.
43. Bhatnagar A, Whitsel L, Ribisl K, et al; American Heart Association Advocacy Coordinating Committee; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Quality of Care and Outcomes Research. Electronic cigarettes: a policy statement from the American Heart Association. Circulation. 2014;130(16):1418-1436.
44. E-cigarettes pose risks. SAMHSA News. https://www.samhsa.gov/samhsaNewsLetter/Volume_22_Number_3/e_cigarettes. Published 2014. Accessed April 7, 2017.
45. National Institute on Drug Abuse. Electronic cigarettes (e-cigarettes). https://www.drugabuse.gov/publications/drugfacts/electronic-cigarettes-e-cigarettes. Revised May 2016. Accessed April 7, 2017.
46. American Academy of Addiction Psychiatry. Nicotine dependence. East Providence, RI: American Academy of Addition Psychiatry; 2015.
47. Green SH, Bayer R, Fairchild AL. Evidence, policy, and e-cigarettes — will England reframe the debate. N Engl J Med. 2016;374(14):1301-1303.
48. Cahill K, Stevens S, Lancaster T. Pharmacological treatments for smoking cessation. JAMA. 2014;311(2):193-194.
1. Hajek P, Goniewicz ML, Phillips A, et al. Nicotine intake from electronic cigarettes on initial use and after 4 weeks of regular use. Nicotine Tob Res. 2015;17(2):175-179.
2. Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Saf. 2014;5(2):67-86.
3. St Helen G, Havel C, Dempsey DA, et al. Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes. Addiction. 2016;111(3):535-544.
4. Grana R, Benowitz N, Glantz SA. E-cigarettes: a scientific review. Circulation. 2014;129(19):1972-1986.
5. Zhu SH, Sun JY, Bonnevie E, et al. Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation. Tob Control. 2014;23(suppl 3):iii3-iii9. doi: 10.1136/tobaccocontrol-2014-051670.
6. Schoenborn CA, Gindi RM. Electronic cigarette use among adults: United States, 2014. NCHS Data Brief. 2015;(217):1-8.
7. Farsalinos KE, Poulas K, Voudris V, et al. Electronic cigarette use in the European Union: analysis of a representative sample of 27 460 Europeans from 28 countries. Addiction. 2016;111(11):2032-2040.
8. Cummins SE, Zhu SH, Tedeschi GJ, et al. Use of e-cigarettes by individuals with mental health conditions. Tob Control. 2015;23(suppl 3):iii48-iii53. doi: 10.1136/tobaccocontrol-2013-051511.
9. Spears CA, Jones DM, Weaver SR, et al. Use of electronic nicotine delivery systems among adults with mental health conditions, 2015. Int J Environ Res Public Heal. 2017;14(1):10.
10. Hefner K, Valentine G, Sofuoglu M. Electronic cigarettes and mental illness: reviewing the evidence for help and harm among those with psychiatric and substance use disorders [published online February 2, 2017]. Am J Addict. doi: 10.1111/ajad.12504.
11. Anthenelli R. How—and why—to help psychiatric patients stop smoking. Current Psychiatry. 2005;4(1):77-87.
12. Singh T, Arrazola RA, Corey CG, et al. Tobacco use among middle and high school students—United States, 2011-2015. MMWR Morb Mortal Wkly Rep. 2016;65(14):361-367.
13. Greenhill R, Dawkins L, Notley C, et al. Adolescent awareness and use of electronic cigarettes: a review of emerging trends and findings. J Adolesc Heal. 2016;59(6):612-619.
14. U.S. Department of Health and Human Services. E-cigarette use among youth and young adults: a report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2016.
15. Cooper M, Harrell MB, Pérez A, et al. Flavorings and perceived harm and addictiveness of e-cigarettes among youth. Tob Regul Sci. 2016;2(3):278-289.
16. Kim H, Davis AH, Dohack JL, et al. E-cigarettes use behavior and experience of adults: qualitative research findings to inform e-cigarette use measure development. Nicotine Tob Res. 2017;19(2):190-196.
17. Czoli CD, Fong GT, Mays D, et al. How do consumers perceive differences in risk across nicotine products? A review of relative risk perceptions across smokeless tobacco, e-cigarettes, nicotine replacement therapy and combustible cigarettes. Tob Control. 2017;26(e1):e49-e58.
18. Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013;382(9905):1629-1637.
19. Caponnetto P, Campagna D, Cibella F, et al. EffiCiency and safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One. 2013;8(6):e66317. doi: 10.1371/journal.pone.0066317.
20. Adriaens K, Van Gucht D, Declerck P, et al. Effectiveness of the electronic cigarette: an eight-week Flemish study with six-month follow-up on smoking reduction, craving and experienced benefits and complaints. Int J Environ Res Public Health. 2014;11(11):11220-11248.
21. Tseng TY, Ostroff JS, Campo A, et al. A randomized trial comparing the effect of nicotine versus placebo electronic cigarettes on smoking reduction among young adult smokers. Nicotine Tob Res. 2016;18(10):1937-1943.
22. Meier E, Wahlquist AE, Heckman BW, et al. A pilot randomized crossover trial of electronic cigarette sampling among smokers. Nicotine Tob Res. 2017;19(2):176-182.
23. Hartmann-Boyce J, McRobbie H, Bullen C, et al. Electronic cigarettes for smoking cessation [published online September 14, 2016]. Cochrane Database Syst Rev. 2016;9:CD010216.
24. Biener L, Hargraves JL. A longitudinal study of electronic cigarette use among a population-based sample of adult smokers: association with smoking cessation and motivation to quit. Nicotine Tob Res. 2014;17(2):127-133.
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