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

Abstract

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 open-label 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; addiction; nicotine; psilocybin; psychedelic; smoking cessation; tobacco.

Figure 1

Smoking cessation measures. Median (interquartile range) of urinary cotinine (A) and breath CO (B) at all time points are shown. Prep Mtg=Preparation Meeting. TQD=Target Quit Date. Threshold values for determining non-smoking status are indicated at dotted line (<200ng/mL cotinine; ≤6ppm breath CO). Mean (SEM) of Questionnaire on Smoking Urges (QSU) scores (C), Wisconsin Smoking Withdrawal Scale (WSWS) scores (D), Smoking Abstinence Self-Efficacy (SASE) temptation (E) and confidence (F) scores at Prep Mtg 1, at 1, 3, 4, 5, 6, 7, 9, and 10 weeks post-TQD, and at 6-month follow-up are shown. C, The QSU contains 32 items (e.g., “Smoking would make me feel happier now”), rated on a 7-point scale ranging from strongly disagree, to strongly agree (Range=32–224). D, The WSWS contains 28 items (e.g., “I have been tense or anxious”) rated on a 5-point scale ranging from strongly disagree, to strongly agree (Range=28–140). E, The SASE assesses temptation to smoke and confidence in smoking abstinence (F) in 20 hypothetical situations (e.g., “At a bar or cocktail lounge having a drink”) rated on a 5-point scale ranging from not at all, to extremely (Range=20–100).

Figure 2

Smoking self-report data. Mean (SEM) of Timeline Follow-back data at intake and 6-month follow-up for the entire study sample, N=15 (A), and for participants who tested positive for smoking at 6-month follow-up, n=3 (B). 6mo=6-month follow-up. Results shown are for 2-tailed paired T-tests comparing average daily smoking.