Pilot Trial Finds Psilocybin Superior to Nicotine Patch for Smoking Cessation

Tobacco use remains a leading cause of premature death. There is preliminary evidence for classic serotonin 2A receptor agonist psychedelics (e.g., psilocybin) for treatment of tobacco use disorder. A pilot, unblinded, randomized clinical trial was conducted among adults (N=82) with daily smoking (>5 cigarettes per day) with at least one prior unsuccessful smoking cessation attempt. Researchers compared the efficacy of nicotine replacement therapy (NRT) with a single high-dose psilocybin session (30mg/70kg) in combination with a 13-week manualized cognitive behavioral therapy (CBT) program for smoking cessation. The primary outcome was smoking abstinence at six-month follow-up, measured via biomarkers and self-report.

• The mean age of the cohort was 48 years; 60 percent were male, 89 percent were White, and 65 percent had lifetime psychedelic use. Participants smoked a mean of 16 cigarettes per day and had a median of six prior quit attempts.
• At week three, participants were randomized 1:1 to either NRT or psilocybin. Participants (n=42) randomized to psilocybin received psychedelic preparation at study visits three and four with the facilitated individual psilocybin dosing session during visit five (week of quit date). Participants (n=40) randomized to NRT received an 8- to 10-week patch regimen during visit five.
• Overall, 68 participants (83 percent) completed all treatments and the six-month follow-up (35 in the psilocybin group, 33 in the NRT group). At six months, 17 participants in the psilocybin treatment group and 4 in the NRT group had biochemically verified smoking cessation. The psilocybin group had 6.12 greater odds of prolonged cigarette abstinence compared with the NRT group.
• There were no reported serious adverse events.

Comments: This pilot study found that select patients receiving psilocybin had higher rates of abstinence from combustible cigarettes at six months than those receiving NRT. Generalizability of results are limited given that participants lacked ethnic/racial diversity, were highly educated, and had greater-than-average prior experiences with psychedelics.

Ximena A. Levander, MD

Reference: Johnson MW, Naudé GP, Hendricks PS, Garcia-Romeu A. Psilocybin or nicotine patch for smoking cessation: a pilot randomized clinical trial. JAMA Netw Open. 2026;9(3):e260972.