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

BACKGROUND. Annual tobacco-related deaths are estimated at 480,000 in the US and 8 million worldwide, dwarfing mortality for all other drugs of abuse. Most smoking cessation interventions result in modest long-term success rates. A pilot study in 15 treatment-resistant smokers found psilocybin with cognitive behavioral therapy resulted in 80% point-prevalence abstinence rates at 6 months.
METHODS. This comparative efficacy study randomized 82 cigarette smokers to receive either 30 mg/70 kg psilocybin (n=42) or FDA-approved nicotine patch treatment (n=40). Both groups received a 13-week manualized cognitive behavioral therapy (CBT) program for smoking cessation. Introspective psilocybin sessions occurred on the target-quit-date. Biochemically verified prolonged smoking abstinence (primary) and point-prevalence abstinence (secondary) at 6 months were compared between groups using intent-to-treat analysis.
RESULTS. Participants on average were 48 years old, smoked 16 cigarettes daily, and had 8 previous unsuccessful quit attempts. The sample was 40% female and 89% White. Demographics did not differ significantly between groups. At 6-month follow-up, prolonged abstinence rates were 40.5% for psilocybin vs 10% for nicotine patch (odds ratio [OR], 6.1 [95% CI, 2.0 - 23.3], p = .003), and point-prevalence abstinence rates were 52.4% for psilocybin vs 25.0% for nicotine patch (OR=3.3 [95% CI, 1.3 – 8.7], p = .013). No serious adverse events were attributed to psilocybin or nicotine patch.
CONCLUSIONS. One psilocybin session, compared to nicotine patch treatment, with manualized CBT, significantly and substantially increased long-term tobacco abstinence. Abstinence rates were considerably higher than typical smoking cessation treatments, indicating robust promise of psilocybin for tobacco smoking cessation.
TRIAL REGISTRATION. ClinicalTrials.gov Identifier: NCT01943994