Psilocybin superior to nicotine patch for helping smokers quit

A single dose of psilocybin, when combined with cognitive behavioural therapy (CBT), may significantly increase the rate of long-term abstinence compared with nicotine patch treatment, according to the results of a randomized clinical trial.

At the 6-month follow-up, the primary outcome of prolonged abstinence, defined as no smoking following an initial 14-day grace period after the target quit date, was achieved by 40.5 percent of participants who received psilocybin vs 10 percent of those who used the nicotine patch. [JAMA Netw Open 2026;9:e260972]

Similarly, more participants in the psylocibin vs nicotine patch group had biochemically verified 7-day point prevalence abstinence, defined as no self-reported smoking (not even a puff) in the 7 days preceding a visit (52.4 percent vs 25 percent).

Compared with nicotine patch, psilocybin was associated with sixfold greater odds of achieving prolonged abstinence (odds ratio [OR], 6.12, 95 percent CI, 1.99–23.26; p=0.003) and more than threefold greater odds of 7-day point prevalence abstinence (OR, 3.30, 95 percent CI, 1.32–8.70; p=0.01).

“Psilocybin appeared safe using established guidelines, with no serious adverse events (AEs),” noted first study author Dr Matthew Johnson from Johns Hopkins University School of Medicine, Baltimore, Maryland, US, and colleagues. [J Psychopharmacol 2008;22:603-620]

“Psychedelic therapy requires few administrations, largely limiting AEs to supervised sessions. In contrast, typical smoking cessation medications are used daily for multiple weeks, resulting in potential for delayed AEs and adherence issues,” Johnson and colleagues pointed out. [SAGE Open Med 2018;6:2050312118777953; Curr Drug Saf 2016;11:78-85]

A greater number of AEs occurred on the target quit date in the psilocybin vs the nicotine patch group (87.5 percent vs 27.5 percent). These AEs were clinically nonsignificant, well-managed, and largely expected psilocybin effects, such as transient blood pressure elevation, headache, and nausea, according to the authors.

“The results of this study add to the increasing evidence that psychedelic treatment may have general antiaddiction efficacy across various addictive drugs,” said Johnson and colleagues.

“Psilocybin’s lack of direct interaction with nicotinic acetylcholine receptors (or receptors mediating the effects of other addictive drugs) highlights psychedelic therapy as a unique approach wherein the pharmacotherapy does not directly alter drug reinforcement or withdrawal but may instead act via higher-order psychological systems, such as changes in self-concept and enhanced psychological flexibility,” they added. [J Psychopharmacol 2018;32:756-769; Psychopharmacology 2020;237:1161-1169; Sci Rep 2024;14:8833]

Nevertheless, Johnson and colleagues acknowledged that their study could not inform the contribution or necessity of psychotherapy, given that both treatment groups received CBT. “It is feasible that psilocybin would be efficacious with less intensive therapeutic support, improving scalability and accessibility,” they said, underscoring the need for further studies to investigate this.

The study included 82 psychiatrically healthy adult smokers (mean age 47.6 years, 59.8 percent male). These participants were randomly assigned to receive one high dose (30 mg/70 kg) of psilocybin or initiate 8–10 weeks of US FDA–approved nicotine patch treatment on the target quit date. Both groups underwent a 13-week manualized CBT program for smoking cessation.

At baseline, participants smoked a mean of 15.7 cigarettes per day and reported a median of six previous quit attempts. Sixty-eight participants (82.9 percent) completed the 6-month follow-up, including 35 in the psilocybin group and 33 in the nicotine patch group.