Pilot study of the 5-HT_2AR agonist psilocybin in the treatment of tobacco addiction

TLDR

Early evidence suggests hallucinogens may treat substance use disorders, but rigorous follow‑up studies are lacking. The study aimed to evaluate the safety and feasibility of psilocybin as an adjunct to smoking cessation and to establish a framework for future research on hallucinogen‑facilitated addiction treatment. An open‑label pilot enrolled 15 nicotine‑dependent smokers who received 20 mg/70 kg or 30 mg/70 kg psilocybin within a 15‑week structured cessation protocol. Six months after treatment, 80 % of participants achieved seven‑day point‑prevalence abstinence, a rate that exceeds typical cessation outcomes (<35 %) and indicates psilocybin may be a promising adjunct.

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 &lt;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.