A single dose of psilocybin outperforms nicotine patches for quitting smoking

A single dose of the psychedelic compound psilocybin, when paired with behavioral counseling, helped smokers quit at substantially higher rates than a standard nicotine patch paired with the same counseling. The results suggest that psychedelic treatments might offer a highly effective new approach for people struggling to overcome tobacco addiction. The findings were recently published in the journal JAMA Network Open.

Tobacco smoking is a leading cause of preventable death worldwide, responsible for an estimated eight million deaths each year. Most people who smoke want to quit, but breaking the biological and psychological grip of addiction is notoriously difficult. Currently available cessation aids, such as nicotine replacement patches and prescription medications, provide modest benefits but often fail to help individuals maintain abstinence over the long term.

The lack of highly effective, long-lasting treatments has prompted researchers to explore entirely new pharmacological strategies. Over the past decade, a growing body of evidence has hinted that psychedelic drugs might help reset established patterns of behavior in mental health conditions, including substance use disorders. Classic psychedelics like psilocybin, the active ingredient in “magic mushrooms,” interact with specific serotonin receptors in the brain. They differ from conventional addiction medications because they do not directly alter the brain’s nicotine reward pathways or dampen physical withdrawal symptoms.

Instead, the therapeutic effects of psychedelics are thought to arise from psychological changes, such as increased psychological flexibility and a shifted sense of self. Early observational studies and small medical trials have reported that people using psychedelics often successfully quit smoking. A small, prior pilot study conducted by researchers at the Johns Hopkins University School of Medicine found high rates of smoking cessation after psilocybin treatment, but that study did not include a control group for direct comparison.

Researchers Matthew W. Johnson, Gideon P. Naudé, Peter S. Hendricks, and Albert Garcia-Romeu sought to test the efficacy of psilocybin against a widely used standard of care. Johnson and Garcia-Romeu led the investigation at the Johns Hopkins Bayview Medical Center in Baltimore. The team designed a clinical trial to compare a single high dose of psilocybin to a standard course of nicotine patches, ensuring participants in both groups received the same structured psychological support. They aimed to see if the psychedelic intervention could outperform an established medical therapy.

The trial enrolled 82 adult daily smokers who had experienced at least one previous unsuccessful attempt to quit. These participants smoked a baseline average of nearly sixteen cigarettes per day and reported a median of six previous attempts to break their habit. Many had smoked for years before entering the study, illustrating the stubborn nature of their nicotine dependence.

The individuals were screened to ensure they were physically and psychiatrically healthy, excluding those with severe mental health conditions or cardiovascular risks. The researchers randomly assigned 42 participants to receive psilocybin and 40 participants to receive standard nicotine patches. Both treatment groups participated in a thirteen-week program of cognitive behavioral therapy designed specifically for smoking cessation.

The structured counseling was based on techniques previously verified in addiction research. It guided participants to weigh the immediate urges to smoke against their long-term personal values. Facilitators worked with the individuals to map out daily triggers and practice alternative coping mechanisms.

Participants attended four preparatory counseling sessions before reaching their target quit date in the fifth week of the program. On the target quit date, the psilocybin group received a single medical dose of the psychedelic compound, adjusted for their body weight. These participants typically spent the day lying on a couch wearing eye shades and listening to a curated music program, supervised by two trained facilitators.

The facilitators met with the participants the following day to discuss the psychedelic experience and to see how they might use insights from the session to support their goal of quitting smoking. Meanwhile, participants in the control group began an eight to ten-week regimen of nicotine patches on their target quit date. The patch dosing was scaled based on how many cigarettes each person typically smoked per day.

Both groups continued to meet with facilitators for counseling sessions periodically over the next two months to review their progress. All participants also received brief daily phone calls or text messages during the week immediately following their target quit date. This extra layer of communication was designed to encourage them through the most difficult days of early withdrawal.

The researchers measured smoking abstinence using multiple methods to ensure accuracy. They relied on participant self-reports combined with biochemical verification. At regular follow-up visits, the team tested their exhaled breath for carbon monoxide, a marker of recent smoking.

They also tested their urine for cotinine, a chemical byproduct of nicotine breakdown. Carbon monoxide levels in the breath provide a reliable snapshot of smoking over the previous twenty-four hours. Cotinine offers a window into tobacco use over the roughly preceding week. Using these biological signals prevents researchers from relying entirely on potentially inaccurate surveys.

When the researchers evaluated the participants six months after the target quit date, the group treated with psilocybin showed markedly higher quit rates. About 40 percent of the individuals in the psilocybin group achieved prolonged, biochemically verified smoking abstinence. This prolonged abstinence metric required participants to remain entirely smoke-free starting two weeks after their target quit date.

In contrast, only 10 percent of the participants in the nicotine patch group maintained the same prolonged abstinence. Statistical analyses indicated that the individuals receiving the psychedelic treatment had odds of successfully quitting that were more than six times greater than those using the patch.

The researchers also measured a secondary outcome known as point prevalence abstinence, which checks if a person has avoided smoking for the seven days immediately preceding a follow-up visit. About 52 percent of the psilocybin group met this standard at the six-month mark, compared to 25 percent of the nicotine patch group. Those in the psilocybin group also smoked about half as many daily cigarettes as those using the nicotine patch in the period following the target quit date.

The safety profile of the psychedelic treatment aligned with established guidelines for human hallucinogen research. The most common physical complaints on the day of the psilocybin dose were anticipated and manageable issues like headaches and transient increases in blood pressure. No serious medical emergencies were attributed to the psychedelic or the nicotine patch during the course of the trial.

Psychedelic therapies typically require only one or two drug administration sessions, which isolates potential side effects to a tightly controlled clinical environment. Standard medications for smoking cessation must be taken daily over weeks or months. That extended schedule introduces the ongoing risk of delayed adverse effects and makes it harder for individuals to stick to the regimen.

While the outcomes strongly support the potential of psychedelic therapy, the researchers noted several limitations in the pilot study. The trial was unblinded, meaning both the participants and the facilitators knew which treatment was being administered. Because psychedelic experiences are intensely noticeable, creating a convincing placebo or blinded control condition remains a major methodological challenge. This transparency means patient expectations might have influenced the success rates.

The sample of participants also lacked broad demographic diversity. The group was predominantly white and highly educated, which could affect how well the results generalize to the broader population of smokers. Additionally, about 65 percent of the participants had a prior lifetime history of using psychedelic drugs. Although the mathematical models suggested this history did not alter the treatment outcomes, it indicates that individuals comfortable with psychedelics might have been more inclined to volunteer for the trial.

Another factor is the difference in contact time between the two groups. Because the psilocybin session lasted all day and required a follow-up integration session the next morning, participants in the psychedelic group spent more total time interacting with the research staff. It is possible that this extra attention and therapeutic support contributed to their higher success rates.

Future double-blind studies involving larger and more diverse groups of people will help clarify these variables. Investigators intend to explore whether the intense psychological support provided alongside the psilocybin can be streamlined to make the treatment more accessible and affordable. They will also look closer at the neurological mechanisms at play, hoping to explain exactly how psychedelics alter addictive behaviors.

The study, “Psilocybin or Nicotine Patch for Smoking Cessation: A Pilot Randomized Clinical Trial,” was authored by Matthew W. Johnson, Gideon P. Naudé, Peter S. Hendricks, and Albert Garcia-Romeu.