Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction, Matthew W. Johnson et al., 2014

Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction

Matthew W Johnson, Albert Garcia-Romeu, Mary P Cosimano and Roland R Griffiths

Journal of Psychopharmacology, 2014, Vol. 28(11) 983–992

© The Author(s) 2014
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DOI: 10.1177/0269881114548296


Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an openlabel pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction.

Keywords : Hallucinogen, tobacco, smoking cessation, nicotine, addiction, psilocybin, psychedelic


A promising research area from the 1950s through 1970s involved the therapeutic use of 5-HT2AR agonist hallucinogens in the treatment of drug dependence, including alcohol and opioid dependence (Chwelos et al., 1959; Hollister et al., 1969; Ludwig et al., 1969; Savage and McCabe, 1973; Smart et al., 1966). Some studies did not include the rigor and controls expected of modern clinical research, thus obscuring efficacy. However, a recent meta-analysis of randomized controlled trials found that LSD-facilitated treatment of alcoholism approximately doubled the success rates of control conditions at the first follow-up (Krebs and Johansen, 2012). Despite suggestive findings, this line of investigation was abandoned due to controversy surrounding the recreational use of hallucinogens and regulatory restrictions impeding subsequent research with 5-HT2AR agonists (Mangini, 1998; Nutt et al., 2013).

Recently, the 5-HT2AR agonist psilocybin was found to occasion mystical-type experiences with enduring personal meaning and spiritual significance in the majority of healthy volunteers (Griffiths et al., 2006). Moreover, at 14-month follow-up, 61% of volunteers associated these experiences with moderate to extreme positive behavior change (Griffiths et al., 2008). In another study, a moderate dose of psilocybin was found to significantly decrease anxiety and depression in patients with advanced stage cancer (Grob et al., 2011). Results from these studies are atypical for pharmacotherapies in that positive effects were observed well beyond the time-course of acute drug effects. Although participants were not drug dependent, these results suggest the feasibility of a psilocybin-facilitated intervention for addiction treatment, consistent with findings that increased levels of spirituality are associated with improved outcomes in drug dependence recovery (Cole et al., 2006; Galanter, 2006; Piderman et al., 2007;
Piedmont, 2004).

Smoking-related mortalities in the USA are currently estimated at 480,000 annually (US Department of Health and Human Services, 2014), and 5 million annually worldwide (World Health Organization, 2011), highlighting the urgent need for novel treatments. Furthermore, most behavioral interventions and pharmacotherapies for smoking cessation exhibit only modest success rates at 6 months (typically <35%; Cahill et al., 2014; Mottillo et al., 2009). The present study was conducted as an open-label pilot study to determine the safety and feasibility (i.e. potential efficacy) of psilocybin-facilitated smoking cessation treatment. Although there is experimental evidence suggesting safety and efficacy of classic hallucinogens in the treatment of addiction, this is largely in relation to the use of LSD for treating alcoholism (Krebs and Johansen, 2012; Mangini, 1998). There has heretofore been no research on use of classic hallucinogens in the treatment of tobacco addiction. Therefore, this pilot study was conducted without a control condition as a first step to evaluate both the safety of the approach, and whether efficacy rates would be promising enough to warrant the investment of resources necessary for a randomized trial.