Psilocybin for Smoking Cessation: What the Research Actually Shows

Psilocybin for smoking cessation is the sleeper story of psychedelic addiction research. A single small pilot at Johns Hopkins, published in 2014, reported abstinence rates more than double what the best FDA-approved cessation drug delivers. A decade later, the National Institute on Drug Abuse is funding the multi-site trial that will decide whether the finding holds.

This guide reports what the evidence actually says. It does not tell you that psilocybin is a proven cure. The pilot was tiny. The long-term follow-up is real but modest. And the practical path to access is currently limited to clinical trial enrollment. Read this the way we would: as a signal that is unusually strong, in a field that has been starved of new tools for a long time.

The 2014 Johns Hopkins pilot

The pilot study of psilocybin for tobacco addiction was led by Matthew Johnson at Johns Hopkins and published in the Journal of Psychopharmacology in 2014. The full title is "Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction."¹

Fifteen adult smokers enrolled. They had smoked for an average of 31 years and had made multiple prior quit attempts. Each participant went through a 15-week cognitive-behavioral therapy protocol adapted from the Mayo Clinic Nicotine Dependence Center program. Two or three moderate-to-high-dose psilocybin sessions were embedded at scheduled quit dates. The doses were 20 mg/70 kg for the first session and 30 mg/70 kg for the second and optional third.

The headline result was biologically-verified 7-day point-prevalence abstinence. At 6 months, 80% of participants (12 of 15) were confirmed abstinent by exhaled carbon monoxide and urine cotinine measurement. Not self-report. Biomarker.

A follow-up paper in 2017 in the American Journal of Drug and Alcohol Abuse tracked the same cohort at 12 and 30 months. Sixty-seven percent were still abstinent at 12 months and 60% at 30 months.² For comparison, the FDA-approved drug varenicline benchmarks about 35% biologically-verified abstinence at 6 months in Cochrane meta-analyses.³

Why the effect matters — and why we need bigger trials

The Johns Hopkins pilot is the strongest single result in the psychedelic addiction literature outside of ibogaine for opioid use disorder. But it is one small, open-label study.

Fifteen participants is not enough to rule out selection effects. An open-label design — where participants and researchers know what they are receiving — cannot separate the pharmacological effect of psilocybin from expectancy, therapist attention, and the intensity of a 15-week CBT protocol. All of those matter for smoking cessation on their own.

The paper did report one internally consistent signal. Participants who scored higher on the Mystical Experience Questionnaire during their psilocybin sessions were more likely to be abstinent at follow-up. That correlation shows up in psilocybin trials for depression and alcohol use disorder too. It is suggestive of a mechanism, but a correlation inside a 15-person study is not confirmation. The confirmatory RCT is what will decide this.

The ongoing NIDA-funded confirmatory RCT

The randomized controlled trial testing psilocybin for smoking cessation is a multi-site study running at Johns Hopkins, the University of Alabama Birmingham, and NYU. It is funded by a National Institute on Drug Abuse R01 grant awarded to Matthew Johnson's group.

The NIDA grant is historically notable in its own right. It was widely reported as the first grant from any NIH institute for a psychedelic treatment trial after a gap of roughly 50 years, since the early-1970s shutdown of federal psychedelic research. The timing tells you how the science establishment now reads this indication.

The trial compares psilocybin plus CBT against a nicotine replacement therapy comparator plus CBT. Primary outcomes include biologically-verified 7-day point-prevalence abstinence at 12 months. The trial is registered on ClinicalTrials.gov; check the registry for the current NCT number and site status before you commit to travel. Our clinical trial finder is set up to surface this specific trial.

How the therapy is actually delivered

Psilocybin smoking-cessation therapy is not "take psilocybin and quit smoking." The pilot protocol was 15 weeks long, and the drug sessions were a small part of the total contact time.

Participants started with several weeks of manualized cognitive behavioral therapy. The protocol was based on the Mayo Clinic Nicotine Dependence Center program, adapted to include psilocybin. CBT covered identifying triggers, coping strategies, and building a quit plan.

The target quit date was scheduled to coincide with the first psilocybin session. Sessions lasted six to seven hours in a supervised setting with two therapists present. A second session followed about two weeks later at a higher dose. An optional third session followed at eight weeks.

Between and after sessions, participants met with therapists for preparation and integration work. Integration in this context focused on the material that came up during sessions and how it connected to the participant's relationship with smoking.

Why psilocybin may help people quit smoking

Psilocybin is a 5-HT2A serotonin receptor agonist. Its acute subjective effects are driven by that receptor. But the interesting question for smoking cessation is not what psilocybin does in the six hours of a session — it is what changes in the months that follow.

One important pharmacological fact: psilocybin does not touch the nicotinic acetylcholine receptors that mediate nicotine addiction and withdrawal. Varenicline is a partial agonist at those receptors. Nicotine replacement therapy delivers nicotine itself. Psilocybin has no direct pharmacological effect on the nicotine withdrawal machinery. The effect is downstream.

The mechanism appears to work through changed motivation and self-concept. Participants who reported a full mystical experience during their sessions were more likely to succeed at abstinence. That pattern is consistent with a model where psilocybin temporarily disrupts entrenched patterns of self-identification ("I am a smoker") long enough for a new frame to take hold and then be reinforced by CBT.

This matters for expectations. Psilocybin will not make the first few days of quitting easier at the physiological level. Cravings and withdrawal are still real. What psilocybin appears to change is whether you interpret those cravings as a reason to give up.

Psilocybin vs. varenicline vs. nicotine replacement therapy vs. behavioral counseling

Psilocybin-assisted therapy is not the only option for smoking cessation, and the FDA-approved options work for many people. Here is how the four main paths compare on the evidence available today.

When to choose psilocybin. If you have tried varenicline or nicotine replacement without success, and you can travel to one of the trial sites, enrolling in the NIDA-funded RCT is the current evidence-based route. If you have not tried FDA-approved options yet, doing so first is reasonable — they work for a meaningful minority of smokers and are far more accessible. Psilocybin is not a replacement for those tools; it is a candidate for a specific subset of people who have not responded to them.

How to access psilocybin for smoking cessation today

The only legal, evidence-based path to psilocybin-assisted smoking-cessation therapy in the United States today is enrolling in a clinical trial. Nothing else on the current legal landscape qualifies.

Clinical trial enrollment is the practical option. The NIDA-funded multi-site RCT is recruiting at Johns Hopkins, University of Alabama Birmingham, and NYU. Use our clinical trial finder to check current recruitment status and eligibility criteria. Participants receive the therapy at no cost. Travel to a site is the main practical hurdle.

Oregon and Colorado adult-use service centers cannot treat smoking cessation. Oregon's Measure 109 and Colorado's Proposition 122 created adult-use psilocybin services, not a medical framework. Facilitators are not licensed to treat nicotine dependence as a medical condition. A service-center psilocybin session is not the Hopkins CBT + psilocybin protocol. If you go to one hoping to quit smoking, you are not receiving the intervention that produced the 80% result.

International psilocybin retreats do not currently offer smoking-cessation protocols matching the Hopkins model. Most retreats — including well-regarded ones — are structured around general wellness or personal-growth outcomes, not manualized addiction treatment. Our best psilocybin retreat centers review covers what these programs are actually set up to do.

Safety and screening

Psilocybin has a relatively benign safety profile compared with most drugs used for addiction treatment. It is not cardiotoxic in the way ibogaine is. It does not cause physical dependence. Its main acute risks are psychological.

Clinical trials screen out participants at elevated risk. Typical exclusion criteria include severe cardiovascular disease, personal or first-degree family history of psychotic disorders, bipolar I disorder, pregnancy, and active suicidality. Most trials also exclude participants on serotonergic medications that would require a washout.

During the session itself, blood pressure and heart rate rise moderately. Acute anxiety or transient dysphoria are common and are managed by the two therapists present. Serious adverse events have been rare in the smoking-cessation and adjacent trials.

Psilocybin's own dependence potential is low. It does not produce the compulsive-use pattern that defines addictive drugs. That profile is part of why it is being tested for addiction treatment in the first place — the tool does not carry the risk it is being used to treat.

Bottom line

Psilocybin-assisted therapy for smoking cessation has produced the most striking single result in modern addiction research: 80% biologically-verified abstinence at 6 months in the Johns Hopkins pilot, sustained at 60% out to 30 months. Varenicline benchmarks around 35%.

The pilot is 15 people and open-label. The NIDA-funded RCT at Johns Hopkins, University of Alabama Birmingham, and NYU is the test that will decide whether this holds up at scale. Until it reads out, this is signal — strong signal, but not confirmation.

If you smoke and want to quit today, the practical evidence-based path is: try FDA-approved options with your physician first, and if you have not responded to them, look at the ongoing psilocybin trial. Our clinical trial finder is set up for exactly this. For the broader picture on psilocybin for addiction, see our psilocybin for alcohol use disorder guide (same research group, similar protocol) and our psychedelic therapy for addiction hub.

For the legal-context piece — what is and is not permitted in Oregon, Colorado, and other jurisdictions — our legal psilocybin booking checklist is the fastest way to pressure-test whether a program you are considering is actually operating within a legal framework.