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.

In the evidence

This study is part of the evidence base for 4 syntheses in the library. Here is how each one recorded it.

• State of the evidence: Psilocybin for addiction ↑Supports

  Twelve of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up, a rate the authors note exceeds typical cessation therapies, though the open-label design precludes definitive efficacy conclusions.

  Synthesized October 22, 2026

• State of the evidence: Addiction ↑Supports

  Twelve of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up after psilocybin within a structured smoking cessation protocol, a rate the authors note exceeds typical behavioral or pharmacological quit rates.

  Synthesized October 25, 2026

• State of the evidence: Psilocybin ↑Supports

  80% of participants showed seven-day point prevalence abstinence at 6-month follow-up after psilocybin-assisted smoking cessation treatment.

  Synthesized October 25, 2026

• State of the evidence: Serotonin ↑Supports

  12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up after psilocybin-assisted smoking cessation treatment.

  Synthesized October 19, 2026

Comparable studies

Other non-randomized and open-label trials on psilocybin for addiction, most cited first.