A single dose of psilocybin combined with cognitive behavioral therapy (CBT) helped smokers quit at significantly higher rates than nicotine patches plus CBT in a pilot randomized clinical trial.

Results of a pilot randomized clinical trial show that among adult smokers who failed multiple attempts to quit smoking, those treated with psilocybin had more than six times greater odds of prolonged abstinence 6 months after treatment than control individuals who received nicotine patch therapy.

These preliminary 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,” investigators led by Matthew Johnson, PhD, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, wrote.

The study was published online on March 10 in JAMA Network Open.

A Better Way to Kick the Habit?

Tobacco smoking remains one of the leading causes of preventable death worldwide and is responsible for an estimated 8 million deaths annually, including about 480,000 in the US. Most existing smoking cessation interventions yield only modest long-term success rates.

Classic serotonin 2A receptor agonist psychedelics like psilocybin have shown early promise for treating psychiatric conditions including various addiction types.

This led Johnson and colleagues to compare the effectiveness of psilocybin with an established smoking cessation treatment, the nicotine patch, when both were paired with structured CBT.

They recruited 82 psychiatrically healthy adults (mean age, 47 years; 60% men) who smoked an average of about 16 cigarettes per day and had multiple prior unsuccessful attempts at quitting.

Forty-two were randomly allocated to a single high dose of psilocybin (30 mg/70 kg) and 40 to initiate 8-10 weeks of nicotine patch therapy. The psilocybin group received psychoeducation about the psychedelic head of time. Both groups participated in a 13-week manualized CBT program for smoking cessation.

A total of 68 participants (83%) completed the 6-month follow-up — 35 in the psilocybin group and 33 in the nicotine patch group.

Six months after the target quit date, 17 (40.5%) participants in the psilocybin group achieved biochemically verified prolonged abstinence from smoking compared with four (10%) participants in the nicotine patch group (odds ratio [OR], 6.12; P = .003).

In addition, 22 (52.4%) participants who received psilocybin were confirmed to have not smoked in the previous 7 days at the 6-month follow-up compared with 10 (25%) participants using the nicotine patch (OR, 3.30; P = .01).

Exploratory analysis of cigarette use between the quit date and 6-month follow-up indicated significantly lower smoking rates in the psilocybin group, with model-predicted daily cigarette consumption of about 1.7 cigarettes vs 3.6 cigarettes in the nicotine patch group.

Accelerate Development

Psilocybin appeared safe using established guidelines, with no serious adverse events. As expected, common short-term effects during psilocybin administration included headache, nausea, and temporary increases in blood pressure.

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

They noted that the trial was not blinded, which could influence outcomes through “expectancy” effects. Also, the sample was relatively small, lacked racial-ethnic diversity, and participants were generally highly educated and motivated to quit smoking, which may limit generalizability to the broader population.

In addition, nearly two third of the participants had previously used psychedelics, raising the possibility of recruitment bias. The fact that both treatment groups received CBT makes it tough to determine how much of the effect was due specifically to psilocybin rather than the therapy itself, they noted.

Despite these limitations, the findings support “accelerating development of psychedelic therapies for substance use disorders, including tobacco,” the researchers wrote.

“Key questions, such as optimizing treatment parameters, cost-effectiveness, and scalability, remain to be examined,” they added.

Support for this study was provided by the Heffter Research Institute, Beckley Foundation, and William Harrison. Johnson reported receiving grants from the National Institutes of Health, Heffter Research Institute, and Mydecine Innovations Group and personal fees from Ajna Labs, MindMed, Beckley Psytech, Clairon Clinics, Otsuka Pharmaceutical Development & Commercialization, Reunion Neurosciences, and Negev Capital outside the submitted work.