A single dose of the psychedelic compound psilocybin combined with behavioral counseling led to significantly higher quit rates among smokers than a standard nicotine patch combined with the same counseling. The results suggest that psychedelic treatments may offer a highly effective new approach for people struggling to overcome tobacco addiction. The results of this study were recently published in the journal JAMA network open.
Smoking is the leading cause of preventable death worldwide, killing an estimated 8 million people each year. Most smokers want to quit, but breaking the biological and psychological grip of addiction is notoriously difficult. Currently available smoking cessation aids, such as nicotine replacement patches and prescription medications, are not very effective and often do not help individuals maintain abstinence over the long term.
The lack of highly effective and long-lasting treatments has led researchers to explore entirely new pharmacological strategies. Over the past decade, increasing evidence has suggested that psychedelics may help reset established behavioral patterns 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. These differ from traditional addiction drugs because they do not directly alter the brain’s nicotine reward pathways or alleviate physical withdrawal symptoms.
Rather, the therapeutic effects of psychedelics are thought to result from psychological changes, such as increased psychological flexibility and altered sense of self. Early observational studies and small medical trials have reported that people who use psychedelics are often more successful in quitting smoking. A previous small pilot study conducted by researchers at Johns Hopkins University School of Medicine found higher quit rates after psilocybin treatment, but the study did not include a control group for direct comparison.
Researchers Matthew W. Johnson, Gideon P. Naudé, Peter S. Hendricks, and Albert Garcia-Lomu set out to test the effectiveness of psilocybin against widely used standard treatments. Johnson and Garcia Lomu led the investigation at Johns Hopkins Bayview Medical Center in Baltimore. The research team designed a clinical trial to compare a single high dose of psilocybin with a standard course of nicotine patches, ensuring that participants in both groups received the same structured psychological support. They aimed to see if psychedelic interventions were more effective than established medical treatments.
The study involved 82 adults who smoked daily and who had failed to quit at least once in the past. These participants smoked a baseline average of nearly 16 cigarettes per day and reported a median of 6 previous attempts to quit the habit. Many had smoked for years before participating in the study, demonstrating the stubborn nature of nicotine addiction.
Individuals were tested to ensure they were physically and psychiatrically healthy, with the exception of those at risk for severe mental health conditions or cardiovascular disease. Researchers randomly assigned 42 participants to receive psilocybin and 40 participants to receive a standard nicotine patch. Both treatment groups participated in a 13-week program of cognitive behavioral therapy specifically designed for smoking cessation.
Structured counseling was based on techniques previously validated in addiction research. It led participants to weigh their immediate urge to smoke against their long-term personal values. Facilitators worked with individuals to plan daily triggers and practice alternative coping mechanisms.
Participants attended four preparatory counseling sessions before reaching their target quit date during week 5 of the program. On the target quit date, the psilocybin group received a single weight-adjusted medical dose of the psychedelic compound. These participants typically spent the day wearing eyeshades and lying on a couch listening to a carefully selected music program overseen by two trained facilitators.
The next day, facilitators met with participants to discuss their psychedelic experiences and see how insights from the sessions could be used to support their goal of quitting smoking. Meanwhile, participants in the control group began taking nicotine patches for 8 to 10 weeks after their target quit date. Patch dosage was adjusted based on the number of cigarettes each person typically smokes per day.
Both groups continued regular counseling sessions with a facilitator over the next 2 months to monitor progress. All participants also received a short phone call or text message each day during the week immediately following their target quit date. This additional layer of communication was designed to encourage them through the most difficult days of early withdrawal.
The researchers used multiple methods to measure smoking cessation to ensure accuracy. They relied on participant self-report combined with biochemical validation. At regular follow-up visits, the team tested breath for carbon monoxide, a marker of recent smoking.
They also tested the urine for cotinine, a chemical byproduct of nicotine breakdown. Exhaled carbon monoxide levels provide a reliable snapshot of smoking over the past 24 hours. Cotinine provides a clue to tobacco use over the past week or so. Using these biological signals prevents researchers from relying entirely on potentially inaccurate studies.
When the researchers evaluated participants six months after their quit goal date, the group treated with psilocybin had significantly higher quit rates. Approximately 40 percent of the psilocybin group achieved biochemically validated long-term smoking cessation. This long-term abstinence measure required participants to remain completely abstinent from 2 weeks after their target quit date.
In contrast, only 10% of participants in the nicotine patch group maintained the same long-term abstinence. Statistical analysis showed that people receiving psychedelic treatment were more than six times more likely to successfully quit smoking than those using the patch.
The researchers also measured a secondary outcome known as point prevalence abstinence. This checks whether the patient has avoided smoking in the 7 days immediately preceding the re-examination. About 52 percent of the psilocybin group met this criterion at six months, compared with 25 percent of the nicotine patch group. People in the psilocybin group also smoked about half as many cigarettes a day after their target quit date as those who used nicotine patches.
The safety profile of the psychedelic treatment was consistent with established guidelines for human psychedelic drug research. The most common physical complaints on the day of psilocybin administration were expected and manageable problems, such as headaches and temporary increases in blood pressure. No serious medical emergencies attributable to psychedelics or nicotine patches occurred during the study period.
Psychedelic therapy typically requires only one or two drug administration sessions, isolating potential side effects in a tightly controlled clinical environment. Standard drugs for smoking cessation must be taken daily for several weeks or months. This extended schedule creates a continued risk of delayed side effects and makes it difficult for individuals to adhere to the plan.
Although the results strongly support the potential of psychedelic therapy, the researchers noted that the pilot study had some limitations. The trial was not blinded, meaning both participants and facilitators knew which treatment was being given. Because psychedelic experiences are so salient, creating convincing placebo or blind control conditions remains a major methodological challenge. This transparency means that patient expectations may have influenced success rates.
There was also no broad demographic diversity in the sample of participants. This group is predominantly white and highly educated, which may influence how well the results generalize to the broader population of smokers. Additionally, approximately 65 percent of participants had a lifetime history of psychedelic drug use. Mathematical models suggested that this history did not change treatment outcomes, but showed that people who were more familiar with psychedelics may have been more likely to volunteer for trials.
Another factor is the difference in contact time between the two groups. Participants in the psychedelic group spent more total time interacting with research staff, as the psilocybin session lasted throughout the day and required a follow-up integration session the next morning. This extra consideration and therapeutic support may have contributed to the higher success rate.
Future double-blind studies with larger and more diverse groups of people will help clarify these variables. The researchers plan to investigate whether the intensive psychological support provided along with psilocybin can be streamlined to make the treatment more accessible and affordable. They also plan to take a closer look at the neurological mechanisms at play in hopes of explaining exactly how psychedelic drugs alter addictive behavior.
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.
