Psilocybin in combination with cognitive behavioural therapy may improve smoking abstinence compared to nicotine patches

1. In this randomized controlled trial, psilocybin combined with cognitive behavioural therapy (CBT) is associated with significantly higher smoking abstinence at 6 months compared to the use of a nicotine patch.

2. A single high dose of psilocybin, when paired with structured CBT, outperformed a standard FDA-approved cessation treatment. 

Evidence Rating Level: 1 (Excellent) 

Study Rundown: Smoking remains a leading cause of premature mortality worldwide, contributing to an estimated 8 million deaths annually. Although most smokers express a desire to quit, existing treatments often fail within 6 months. Some serotonin 2A receptor-agonist psychedelics have shown early promise in addiction treatment, prompting investigation into their use alongside cognitive behavioural therapy (CBT) for smoking cessation.

In this study of 82 participants, individuals received up to three psilocybin doses (20-30 mg/70 kg), with minimal adverse effects, or standard nicotine patch therapy, with smoking status assessed through exhaled carbon monoxide, urinary cotinine, and self-report. Adverse effects were similarly self-reported. Prolonged smoking abstinence at six months was the primary study outcome measured, defined by low carbon monoxide and cotinine levels. Some limitations include the nonblinded design, which may have influenced expectations, and limited demographic diversity.

Overall, the psilocybin group exhibited greater abstinence from cigarette use compared to the nicotine patch treatment at 6 months, with minimal reported adverse effects, indicating promise for psilocybin treatment for cigarette cessation. These findings suggest that psilocybin‑assisted therapy may help individuals achieve more durable behaviour change than standard cessation approaches.

Click here to read the study in JAMA Network Open

Relevant Reading: 5-HT2A Agonist Psilocybin in the Treatment of Tobacco Use Disorder

In-Depth [randomized controlled trial]: Eligible participants were daily smokers aged between 21 and 80 with prior failed quit attempts and a desire to stop smoking, while individuals with pregnancy, significant medical issues, cardiovascular risks, or personal or family histories of major psychiatric disorders were excluded. Participants reported a median of 6 previous quit attempts, with a mean of 15.7 cigarettes smoked per day. While no major study-related adverse effects were observed, 85.4% of participants reported some adverse effects, with higher prevalence in the psilocybin groups (87.5 vs 27.5%), including transient increases in blood pressure and heart rate, as well as headaches. After 6 months, 40.5% of the psilocybin group showed verified prolonged abstinence, compared to 10.0% in the nicotine patch group (OR, 6.12; 95% CI, 1.99-23.26; P = .003), with higher 7 day abstinence as well (OR, 3.30; 95% CI, 1.32-8.70; P = .01). Lower daily cigarette consumption was also observed in the psilocybin group (incidence rate ratio, 0.04; 95% CI, 0.004-0.27; P = .002). These results indicate that psilocybin-assisted therapy, even with a single high dose, may offer a substantially more effective approach to smoking cessation than standard nicotine replacement when combined with CBT.

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