A single dose of psilocybin is more effective than nicotine patches for quitting smoking, study suggests

A new study, published in JAMA Network Open, reports the outcome of a clinical trial out of Johns Hopkins University assessing the effectiveness of psilocybin as a treatment for smokers attempting to quit. The trial compared the effectiveness of one dose of the “magic mushroom” drug to months of the common nicotine patch, combined with cognitive behavioral therapy in both groups. The results might push psilocybin into the limelight as a more effective addiction treatment.

The need for more effective smoking cessation treatments

Smoking is a major cause of poor health, leading to around 480,000 deaths annually in the US and 8 million worldwide. Many smokers have a desire to quit, but lack an effective treatment to get them through the difficult process. While existing therapies, like nicotine replacement, varenicline, bupropion, and counseling can help temporarily, they often fail within 6 months.

Some previous studies have shown promise for the use of psilocybin for smoking cessation, with high abstinence rates at 6, 12, and even 30 months. The action of the drug is different than other addiction treatments. Instead of targeting nicotine receptors, the researchers believe psilocybin works by shifting the way the user thinks, allowing them to get out of unhealthy patterns more easily.

“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,” the study authors write.

Psilocybin vs. the nicotine patch

The team conducted the pilot randomized clinical trial at Johns Hopkins Bayview Medical Center from 2015 to 2023. With the goal of assessing smoking cessation at six months, the team enrolled 82 adult smokers who had previously attempted to quit smoking. The participants were randomly put into either the nicotine patch group or the psilocybin group. The psilocybin group were given a single high dose of psilocybin (while monitored) or 8-10 weeks of nicotine patches, both with 13 weeks of cognitive behavioral therapy (CBT).

At 6 months, 38 psilocybin participants remained in the study and 32 nicotine patch participants remained. The participants were interviewed and tested for signs of smoking. Results showed that 40.5% (17) of psilocybin recipients had prolonged abstinence, while only 10% (4) of nicotine patch participants abstained from smoking by this time. At this time, 22 (52.4%) psilocybin participants were biochemically verified to have abstained from smoking for the previous seven days, compared with 10 participants (25.0%) of those that had used the nicotine patch. No serious adverse events occurred, although mild hypertension, headaches, and nausea were reported.

The study authors write, “A single psilocybin dose combined with manualized CBT yielded significantly greater smoking abstinence than the nicotine patch paired with the same CBT. At 6 months, the psilocybin group had more than 6 times greater odds of showing prolonged abstinence (primary outcome) and more than 3 times greater odds of showing 7-day point prevalence abstinence (secondary outcome). Participants in the psilocybin group smoked a mean of approximately 50% fewer cigarettes per day (CPD) between the target quit date and 6-month follow-up.”

What comes next for psilocybin

While the team is optimistic about the results of the study, they do note some limitations. This was a nonblinded study, mostly due to the effects of psilocybin being obvious for participants. The study was small and the sample lacked ethnoracial diversity and was highly educated. A larger, more diverse sample is a goal for future related studies. The researchers also note that a high proportion of participants had prior psychedelic experience, which may limit generalizability.

Despite limitations, the study suggests psilocybin may be a useful tool for addiction cessation. The researchers say that the treatment should move forward in the FDA process toward potential approval.

“Nevertheless, findings support accelerating development of psychedelic therapies for substance use disorders, including tobacco. Key questions, such as optimizing treatment parameters, cost-effectiveness, and scalability, remain to be examined,” the study authors conclude.

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