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

## TL;DR

A pilot study found that psilocybin treatment with cognitive behavioral therapy led to significantly higher smoking cessation rates than nicotine patches with the same therapy.

## Contribution

This is the first pilot trial comparing psilocybin with nicotine patches for smoking cessation in a controlled setting.

## Key findings

- Psilocybin users had 6.12 times higher odds of prolonged abstinence at 6 months compared to nicotine patch users.
- No serious adverse events were attributed to psilocybin treatment.
- Psilocybin abstinence rates exceeded typical smoking cessation treatments.

## Abstract

What tobacco smoking cessation rates does psilocybin, an experimental treatment, yield compared with nicotine patch, an established treatment, with individuals in both groups receiving standardized cognitive behavioral therapy?

In this pilot randomized clinical trial, 42 participants randomized to receive psilocybin had more than 6 times greater odds of prolonged smoking abstinence 6 months after treatment than 40 participants who received the nicotine patch.

These results suggest that psilocybin holds potential in the treatment of tobacco use disorder and, along with other psychedelics, should be investigated further for tobacco and other substance use disorders.

This pilot randomized clinical trial compares prolonged smoking abstinence rates in smokers receiving psilocybin with those receiving the nicotine patch with both groups receiving manualized smoking cessation cognitive behavioral therapy.

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.

To compare prolonged smoking abstinence rates in smokers receiving psilocybin plus cognitive behavioral therapy (CBT) with those receiving the nicotine patch plus CBT.

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.

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.

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.

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.

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.

ClinicalTrials.gov Identifier: NCT01943994