A single psilocybin dose beat the nicotine patch for quitting in a small trial

A pilot randomized trial published this month in JAMA Network Open compared a single high dose of psilocybin against the standard nicotine patch for smoking cessation, both paired with cognitive behavioral therapy, in adult smokers treated at Johns Hopkins Bayview Medical Center [s1]. It's a small trial with an unusually long data-collection window, and its result adds to a body of earlier, less rigorously controlled psilocybin-for-smoking research from the same research group.

The design

Eighty-two psychiatrically healthy adult smokers were randomized to receive either one high dose of psilocybin (30 mg per 70 kg body weight) or an eight-to-ten-week course of FDA-approved nicotine patches, both initiated on a target quit date and both accompanied by a 13-week manualized cognitive behavioral therapy program [s1]. Participants and researchers knew which treatment each person received — the trial was not blinded — and participants had the option to cross over to the other treatment after the primary endpoint [s1]. Data collection ran from January 2015 to May 2023 [s1], a span reflecting the trial's long recruitment and follow-up period rather than a delay in publication of completed results. The mean participant age was 47.6 years, and 59.8% were male [s1]. Sixty-eight of the 82 participants, or 82.9%, completed the six-month follow-up [s1].

What it found

At six months, biochemically verified prolonged abstinence — confirmed with a test rather than taken on self-report alone — was achieved by 40.5% of the psilocybin group (17 of the group) compared with 10.0% of the nicotine-patch group (4 of the group), an odds ratio of 6.12 (95% CI 1.99–23.26, p = .003) [s1]. A secondary measure, seven-day point-prevalence abstinence, showed a similar pattern: 52.4% on psilocybin versus 25.0% on the patch, odds ratio 3.30 (95% CI 1.32–8.70, p = .01) [s1]. No serious adverse events were attributed to either psilocybin or the nicotine patch [s1].

How this compares with typical quit rates

The paper's authors note that psilocybin's abstinence rate in this trial exceeds what's typically seen with standard smoking-cessation treatments [s1] — the paper cites no specific comparator figure for context beyond the trial's own nicotine-patch arm, which itself performed roughly in line with expectations for patch therapy generally. The 10% abstinence rate on the patch arm and 40.5% on psilocybin represent a fourfold difference; the odds ratio of 6.12 reflects how that gap translates statistically, though its wide confidence interval (essentially 2-fold to 23-fold) reflects how few events — 17 and 4 people — the estimate rests on.

The limits

This is a pilot trial of 82 people at a single center, unblinded, meaning participants and researchers alike knew which treatment was assigned — a real limitation for measuring a self-reported behavior like smoking, even with biochemical verification of abstinence. Psychiatrically healthy adults were specifically recruited, which means the trial says nothing about psilocybin's use in smokers with co-occurring psychiatric conditions, where psychedelic administration carries specific safety considerations. The Johns Hopkins group has published smaller, open-label psilocybin smoking-cessation data before this trial; this randomized, patch-controlled comparison is the more rigorous test of the same hypothesis, but it remains a single trial from one research group and one site.

What to watch

Whether the effect replicates in a larger, multi-site trial, and how it might perform against varenicline or combination nicotine replacement therapy, which are more effective standard treatments than the patch alone. Psilocybin is not approved for smoking cessation or any other indication in the United States; this article describes investigational drug trial results and is not medical advice.

Sources

1. Psilocybin or Nicotine Patch for Smoking Cessation: A Pilot Randomized Clinical Trial — JAMA Network Open, 10 March 2026