Psilocybin or Nicotine Patch for Smoking Cessation: A Pilot Randomized Clinical Trial.

Importance: Annual tobacco-related death estimates are 480 000 in the US and 8 million worldwide, surpassing mortality for other abused substances. Most smoking cessation interventions result in modest long-term success. Objective: To compare prolonged smoking abstinence rates in smokers receiving psilocybin plus cognitive behavioral therapy (CBT) with those receiving the nicotine patch plus CBT. Design, Setting, and Participants: In this pilot randomized clinical trial, participants and investigators were unblinded to treatment condition, including an optional crossover after completion of the primary end point. Data were collected from psychiatrically healthy adult smokers from January 20, 2015, to May 8, 2023, at the Johns Hopkins Bayview Medical Center, an academic medical center and teaching hospital in Baltimore, Maryland. Intervention: The trial randomized cigarette smokers to receive either 1 high dose (30 mg/70 kg) of psilocybin or initiate 8 to 10 weeks of US Food and Drug Administration-approved nicotine patch treatment on the target quit date. Both groups received a 13-week manualized CBT program for smoking cessation. Main Outcomes and Measures: Biochemically verified prolonged smoking abstinence (primary) and 7-day point prevalence abstinence (secondary) at 6 months after the target quit date were compared between groups using intention-to-treat analysis. Results: A total of 82 psychiatrically healthy adult smokers (mean [SD] age, 47.6 [12.0] years; 49 [59.8%] male) participated in the study, with 68 (82.9%) completing the 6-month follow-up. At 6-month follow-up, 17 participants receiving psilocybin (40.5%) exhibited biochemically verified prolonged abstinence compared with 4 participants using the nicotine patch (10.0%) (odds ratio, 6.12; 95% CI, 1.99-23.26; P = .003), and 22 participants receiving psilocybin (52.4%) exhibited biochemically verified 7-day point prevalence abstinence compared with 10 participants using the nicotine patch (25.0%) (odds ratio, 3.30; 95% CI, 1.32-8.70; P = .01). No serious adverse events were attributed to psilocybin or nicotine patch. Conclusions and Relevance: In this pilot randomized clinical trial, 1 dose of psilocybin with manualized CBT significantly increased long-term abstinence compared with nicotine patch treatment with CBT. Psilocybin abstinence rates were higher than typical treatments, suggesting promise for tobacco smoking cessation. Trial Registration: ClinicalTrials.gov Identifier: NCT01943994.