Tobacco/Nicotine Use Disorder (TUD)
Tobacco use is one of the world’s biggest causes of preventable death, and quitting is famously hard. The most striking psychedelic result here is from psilocybin: a small Johns Hopkins pilot reported that most heavy smokers were still abstinent six months after a couple of supervised doses paired with quit-smoking therapy. In 2026 a controlled trial finally tested it head to head against the nicotine patch and psilocybin won, though the real-world abstinence figure was far lower than the famous pilot, and the trial could not be properly blinded. The signal is real and encouraging, but the evidence is still small and early.
How are psychedelics being studied for tobacco use disorder? Tobacco use disorder is a common and harmful addiction, and even effective treatments leave many people relapsing. The most notable psychedelic research is a small pilot study in which psilocybin, paired with cognitive behavioural therapy, was associated with high quit rates in people trying to stop smoking, prompting larger follow-up trials. The idea is that a supported session may help break entrenched habits, with the surrounding therapy central to the result. The early findings are striking but come from small samples, and larger controlled trials are needed to confirm them. Blossom tracks the trials and papers behind tobacco research so you can follow the evidence.
Data updated
Key Insights
- 1
Tobacco use disorder is a thin but striking area for psychedelics. The lead compound is psilocybin, not ayahuasca or ibogaine: a famous Johns Hopkins pilot found 80% of smokers (12 of 15) biologically confirmed abstinent at six months after psilocybin plus quit-smoking therapy.
- 2
Those gains looked unusually durable for smoking cessation: in the same small group, 67% were still abstinent at one year and 60% at long-term follow-up (around 30 months).
- 3
In March 2026 the long-awaited controlled trial reported: in 82 smokers, psilocybin plus therapy beat the nicotine patch plus therapy on prolonged abstinence, 40.5% versus 10% (odds ratio 6.12). A real win, but the 40.5% is far below the pilot’s 80%.
- 4
The big caveat is blinding: that 2026 trial was openly unblinded, single-site, and used self-selected, psychiatrically healthy volunteers wrapped in an intensive 13-week therapy programme, so how much is the drug versus expectancy and therapy is unresolved.
- 5
Ketamine’s own small tobacco trial was essentially negative, and the ayahuasca and ibogaine evidence for tobacco is observational survey data only, so psilocybin is the only compound here with real cessation trials behind it.
By the numbers
- 5
- Trials tracked
- 64
- Papers tracked
- 257
- Trial participants
as of June 2026
as of June 2026
as of June 2026
What is Tobacco/Nicotine Use Disorder (TUD)?
Tobacco (or nicotine) use disorder is the medical term for addiction to tobacco, the compulsive use of cigarettes or other tobacco products despite the harm it causes, driven by nicotine acting on the brain’s reward system. It is one of the largest preventable causes of death in the world: the World Health Organization estimates that around 1.25 billion people use tobacco and that it kills over 8 million people a year[1].
Most smokers who try to quit relapse, even with the best current tools, which is why new approaches attract attention. Standard treatments such as nicotine replacement and the medicines varenicline and bupropion roughly double a person’s chance of quitting, but most attempts still fail. That persistent gap is what makes a single supervised session with a long after-effect an interesting idea, and it is where psilocybin in particular has been tested.
This page is scoped to tobacco and nicotine specifically and sits within Blossom’s broader Substance Use Disorders hub, which covers the shared mechanisms and the evidence across alcohol, opioids and other substances. One correction worth stating up front: the lead compound for tobacco is psilocybin, which has actual cessation trials, not ayahuasca or ibogaine, whose tobacco evidence is only observational.
Current Treatments
Standard care for tobacco use disorder combines behavioural support (counselling, quit lines, structured programmes) with medication: nicotine replacement therapy (patches, gum, lozenges), and the prescription drugs varenicline and bupropion, which reduce craving and withdrawal. These work, and they are the right first step, but their effects are modest. Even with the best combinations, the majority of quit attempts end in relapse within a year, and many smokers cycle through multiple attempts.
The psychedelic approach is different in shape: not a daily medicine but one or a few supervised dosing sessions inside a course of quit-smoking therapy, aiming to make a single attempt far more likely to stick. None of the compounds on this page is approved for tobacco use disorder anywhere; psilocybin is investigational, studied in clinical trials. What is notable about tobacco is that, for such a small evidence base, it now includes one of the more encouraging controlled results in addiction psychiatry.
This report summarises what Blossom’s database shows about psychedelic and dissociative compounds for tobacco use disorder, and what it does not show. The short version: this is a small evidence base with one genuinely interesting thread. Psilocybin, not ayahuasca or ibogaine, is the lead, on the strength of a famous Johns Hopkins pilot and, newly in 2026, the first controlled trial showing it beating the nicotine patch. The result is real and encouraging, but it rests on tiny, single-site, hard-to-blind studies, and the controlled abstinence figure is far below the headline pilot number.
A note before the evidence
This page is a research summary, not medical advice, and nothing here is a treatment recommendation. Psilocybin is not approved for smoking cessation anywhere; it is investigational and studied only in clinical trials with screening and psychological support. If you want to stop smoking, effective, approved help, including nicotine replacement, varenicline or bupropion and behavioural support, is available now and is the right place to start. Decisions about quitting belong with you and a clinician, not with an unregulated psychedelic.
This page sits within Blossom’s Substance Use Disorders hub and is scoped to tobacco specifically. A word on the numbers: Blossom tracks 64 papers and 5 trials tagged to this topic, and those counts appear on the page. The tag is leaky, pulling in general-addiction reviews, alcohol and opioid studies, population surveys and preclinical pharmacology, so the genuinely tobacco-specific clinical core is very small, on the order of five human studies, most of them a single Johns Hopkins lineage. Read the counts as breadth of coverage, not as the depth of the tobacco evidence.
Psilocybin: a striking pilot, and now a controlled test
The reason tobacco is interesting at all is one line of work. A Johns Hopkins open-label pilot gave 15 long-term heavy smokers two to three supervised psilocybin doses inside a 15-week cognitive behavioural programme, and 80% (12 of 15) were biologically confirmed abstinent at six months[1], a figure far above the under-35% typically seen with standard treatments. A long-term follow-up found 67% abstinent at one year and 60% at roughly 30 months[2], and a mediation analysis found that those who quit had stronger mystical-type experiences, independent of the raw intensity of the drug effect[3].
For years the obvious objection was that this was an uncontrolled, open-label pilot of fifteen self-selected people. In March 2026 the controlled test arrived. A pilot randomised trial (n=82) compared a single high psilocybin dose plus therapy against nicotine patch plus the same therapy, and found psilocybin clearly superior on biochemically verified prolonged abstinence at six months: 40.5% versus 10%, an odds ratio of 6.12[4]. That is a real, controlled win over an active standard treatment, which very few things in addiction psychiatry achieve.
Two things keep it honest. First, the 40.5% is roughly half the pilot’s 80%, a textbook illustration of how an open-label headline shrinks under control conditions. Second, the trial was openly unblinded, with an optional crossover, at a single centre, in psychiatrically healthy volunteers, wrapped in an intensive thirteen-week therapy programme. So the result genuinely strengthens the case, and it does not settle it: the central question of how much is the drug, how much is expectancy, and how much is the therapy remains open.
Ketamine and esketamine: little so far
Ketamine has been tried and has mostly disappointed for tobacco. A small double-blind, midazolam-controlled crossover pilot (n=18) in smokers who were not trying to quit found only a non-significant reduction in cigarettes (p=0.10) and no effect on craving or withdrawal[5]. The one positive signal in the ketamine family comes from a very different population: an esketamine trial in 236 people with both lung cancer and major depression found higher confirmed abstinence than placebo[6], but there the smoking benefit is bound up with treating depression and does not generalise to ordinary smokers. For general tobacco use disorder, ketamine has not shown a clear effect.
Ayahuasca and ibogaine: observational only
Ayahuasca and ibogaine are frequently mentioned for tobacco, and this is where the existing framing has been most misleading. There are no tobacco-cessation trials for either. The ayahuasca evidence is survey data: an online survey associating stronger mystical experiences with quitting[7] and a comparison finding lower tobacco and alcohol use disorder among members of an ayahuasca-using religious group[8]. Both are retrospective, self-selected and unverified, useful for generating hypotheses, not for showing effect. Ibogaine has no tobacco-cessation data at all and appears here only in preclinical and cardiac-safety work.
It is worth stating plainly because it corrects a common inversion: for tobacco, psilocybin is the lead with real trials, and ayahuasca and ibogaine sit well below it on observational evidence. A wider correlational picture is mixed rather than uniformly positive, with a large national survey linking some psychedelics to lower nicotine dependence but LSD to higher[9], which is a reminder that population associations are not treatment effects.
How might it work?
The proposed mechanisms are plausible and still hypotheses. Psilocybin acts on the brain’s 5-HT2A serotonin receptors and appears to open a window of heightened neuroplasticity that, paired with quit-smoking therapy, may help break the automatic link between cue, craving and cigarette. The most consistent tobacco-specific finding is psychological rather than purely pharmacological: across the pilot and the surveys, the depth and meaning of the experience, the mystical-type shift in priorities and self-efficacy, predicts who quits, more than the raw intensity of the drug. That is why the therapy around the dose is treated as part of the treatment, and it is also why blinding is so hard, since a profound subjective experience is exactly what the participant notices.
Reading this honestly
So where does tobacco use disorder sit? On a very small base, it is one of the more encouraging stories in psychedelic medicine, and the only addiction indication besides alcohol with a controlled win to point to. Psilocybin produced a remarkable open-label result and then, unusually, beat an active standard treatment in a randomised trial. But the whole edifice rests on one academic centre, a few dozen patients, an unblinded design and a controlled abstinence rate well below the famous headline. The honest reading refuses both the breathless version, that psilocybin cures smoking, and the dismissive one, that a striking and now partly replicated result is nothing. For the many smokers failed by current treatments, a promising, real, but still unproven option is a reason for measured hope and for the larger trials that would turn a single centre’s encouraging numbers into something the field can rely on.
Psychedelic Effect Matrix
Compound efficacy and evidence levels for Tobacco/Nicotine Use Disorder (TUD).
| Compound | Magnitude | Evidence | Consistency |
|---|---|---|---|
| Psilocybin The clear lead. A Johns Hopkins open-label pilot (n=15) reported 80% abstinence at six months, durable to 60% long-term, and a 2026 pilot RCT (n=82) beat the nicotine patch (40.5% vs 10%, OR 6.12). But the RCT was unblinded and single-site, the controlled figure is far below the pilot, and there is no large blinded trial. | Large | Moderate | Moderate |
| Ketamine A small double-blind crossover pilot (n=18) in smokers not trying to quit was essentially negative: only a non-significant fall in cigarettes (p=0.10) and no effect on craving or withdrawal. A separate esketamine RCT helped smokers with lung cancer and depression, but that is a narrow comorbid population. | Small | Low | Low |
| Ayahuasca No clinical trials in tobacco. The evidence is observational only: online surveys and a religious-cohort comparison associate ayahuasca use with reduced smoking. Hypothesis-generating, recall-biased and self-selected, and well below psilocybin. (Ibogaine has no tobacco-cessation data at all.) | Small | Very Low | Low |
Psilocybin and Tobacco/Nicotine Use Disorder (TUD)
Psilocybin is the flagship, and effectively the only compound with real tobacco-cessation trials. The famous result is a Johns Hopkins open-label pilot (n=15) in which 80% of long-term heavy smokers were biologically confirmed abstinent at six months[1] after a couple of supervised psilocybin doses inside a 15-week cognitive behavioural programme. A long-term follow-up found 67% still abstinent at one year and 60% at around 30 months[2], and abstinence tracked the intensity of the mystical-type experience rather than the raw drug effect[3].
The crucial 2026 update is the first controlled test. A pilot randomised trial (n=82) compared psilocybin plus therapy against the nicotine patch plus therapy and found psilocybin clearly better, 40.5% prolonged abstinence versus 10% (odds ratio 6.12)[4]. That is a genuine, encouraging controlled win. It is also a reality check: the 40.5% is roughly half the pilot’s 80%, the trial was openly unblinded with an optional crossover, and it remains a single-site study of self-selected, psychiatrically healthy volunteers. Real signal, still small and early.
Ketamine and Tobacco/Nicotine Use Disorder (TUD)
Ketamine has been tried for tobacco, with underwhelming results so far. A small double-blind, midazolam-controlled crossover pilot (n=18) in smokers who were not trying to quit found only a non-significant reduction in cigarettes smoked (p=0.10) and no effect on craving or withdrawal[1], although about half of participants said it felt subjectively easier to abstain.
The one positive ketamine-family signal comes from a different setting: an esketamine trial in 236 patients who had both lung cancer and major depression reported higher confirmed abstinence than placebo[2]. But that is a narrow comorbid population where the smoking effect is entangled with treating depression, and it does not show that ketamine helps otherwise-healthy smokers quit. For general tobacco use disorder, ketamine has not yet demonstrated a clear benefit.
Ayahuasca and Tobacco/Nicotine Use Disorder (TUD)
Ayahuasca is often mentioned for tobacco, but its evidence is observational, not clinical. An online survey found that people who used ayahuasca and had a stronger mystical experience were more likely to report quitting smoking[1], and a study of members of an ayahuasca-using religious group found lower rates of tobacco and alcohol use disorder than national norms[2].
These are retrospective, self-selected surveys with no control group, no biological verification and obvious recall bias, so they can suggest a hypothesis but cannot show that ayahuasca helps people quit. Ibogaine, sometimes grouped with it, has no tobacco-cessation data at all. The honest placement is that ayahuasca and ibogaine sit well below psilocybin here, which is the opposite of how this topic is often presented.
Clinical Outlook
The near-term question is whether the 2026 controlled result holds up in a larger, better-designed trial. The pilot randomised trial was explicitly a pilot, unblinded and single-site[1], so the obvious next step is a multi-site trial with a more convincing comparison condition and a serious attempt to address blinding, which is the central unsolved problem for this whole field. Several psilocybin tobacco trials are under way, and the funding and academic interest are real.
The realistic outlook is cautious optimism on a small base. Tobacco is a slightly unusual case: the absolute number of studies is tiny, but the ones that exist are unusually positive, including a controlled win over an active standard treatment. If that result replicates at scale, psilocybin-assisted smoking cessation could become a genuine option for the many smokers who fail conventional methods. If it does not, tobacco will join the list of indications where a striking early signal shrank under proper scrutiny. Either way, the honest current status is promising and unproven.
Industrial Landscape
Tobacco research in this space is overwhelmingly academic, and concentrated in one place: the Johns Hopkins group ran the original pilot, the mediation analysis, the long-term follow-up and the 2026 randomised trial[1]. That single-centre lineage is a strength for depth and consistency, but a weakness for independence: almost all of the tobacco evidence comes from one team, and replication by other groups is exactly what the field now needs.
There is relatively little commercial activity dedicated specifically to tobacco, compared with depression or even alcohol. Smoking cessation is a large public-health problem but a difficult commercial market, with cheap generic competitors and modest reimbursement, so the running is made by university researchers and public or philanthropic funders rather than by a developer racing to a label. For an honest broker, that academic character keeps the work measured, but the reliance on a single centre means the encouraging numbers should be held loosely until others reproduce them.
Quick Indicators
Related Topics
Organisations
Search →National Institute on Drug Abuse (NIDA)
U.S. federal institute setting addiction-research priorities and portfolios, including psychedelic-related investigations.
Ketamine Research Institute
The Ketamine Research Institute is a US-based clinical research organization developing precision medicine approaches to ketamine infusion therapy, studying optimized dosing protocols to treat depression and offering clinician training in evidence-based ketamine practice.
New York University
The Center for Psychedelic Medicine at NYU Langone Health is directed by Dr. Michael Bogenschutz and performs health-focused research across the translational spectrum, from basic science to large-phase clinical trials. The center has three transdisciplinary areas of focus: psychiatry, medicine, and preclinical research. Currently, the team is actively investigating clinical applications for various psychedelic compounds, leading robust studies on psilocybin-assisted therapy for alcohol use disorder, major depression, and advanced cancer-related psychiatric distress.
Johns Hopkins University
The Centre for Psychedelic and Consciousness Research focuses on how psychedelics affect behavior, cognition, brain function, and biological health markers. They have been at the forefront of demonstrating the safety and efficacy of psychedelics for mental disorders, expanding their focus into psilocybin research across multiple mental health conditions, including smoking cessation, major depressive disorder, and cancer-related anxiety.
Beckley Med Foundation
Fundación Beckley Med is a Barcelona-based psychedelic research and education organisation, partnered with the UK's Beckley Foundation, that funds and disseminates psychedelic-assisted therapy studies and provides professional training through institutional affiliations with MAPS, Grof Legacy, and CIIS. It collaborated with CITA Clinic to deliver experimental ketamine treatment to patients with treatment-resistant depression in Spain.
Medical University of Gdansk
The Medical University of Gdańsk is Poland's leading academic medical institution, with its Department of Psychiatry running one of the country's most active research programs on ketamine and esketamine for treatment-resistant depression and bipolar disorder.
University of Alabama at Birmingham
Major research university and academic medical center in Birmingham, Alabama. A key site in the first federally funded psilocybin trial in 50 years — a NIH/NIDA-funded multisite study on psilocybin for smoking cessation led by Dr. Peter Hendricks, alongside Johns Hopkins and NYU.
Wake Forest University Health Sciences
Wake Forest University School of Medicine and its clinical affiliate Atrium Health Wake Forest Baptist form a comprehensive academic health sciences enterprise in Winston-Salem, North Carolina. The institution conducts extensive clinical and translational research in psychiatry, neuroscience, addiction medicine, and novel therapeutic approaches, including studies on psychedelic-assisted treatment.
People
Search →Henrik Jungaberle
Dr. sc. hum., CEO and founder of the MIND Foundation; Head of Development at OVID Clinic Berlin
He is a prominent European psychedelic research and implementation figure contributing to psilocybin clinical trials, harm reduction, and healthcare integration work.
Juliana Rocha
Doutoranda em Ciências Médicas / Saúde Mental at the Ribeirão Preto Medical School, University of São Paulo
She is a recurring coauthor on clinical psychedelic studies, especially ayahuasca trials on social anxiety, emotion recognition, personality, and social cognition, helping expand the human evidence base for psychedelic-assisted psychiatric research.
Mathieu Seynaeve
Senior Medical Director and Head of Psychotherapy at Beckley Psytech
He is a clinical development leader behind multiple human studies of 5-MeO-DMT and psilocybin, including trials in alcohol use disorder, treatment-resistant depression, and headache disorders.
Philippe Lucas
Director, Research and Safe Access at MAPS
He is a prominent Canadian psychedelic and cannabis researcher whose work has helped establish early evidence on ayahuasca-assisted therapy, psychedelic survey research, and harm-reduction policy.
Neşe Devenot
Senior Lecturer in the University Writing Program at Johns Hopkins University
Neşe Devenot is a notable critic and scholar of psychedelic medicine whose work examines ethics, public discourse, and the social meanings of psychedelic-assisted therapy.
Adam Winstock
Professor of Addiction Medicine; Consultant Psychiatrist and Founder/Director of Global Drug Survey
A leading figure in global survey-based research on psychedelics, club drugs, and substance use patterns, with widely cited work informing harm reduction and public health.
Thomas Swift
Assistant Professor in Chemistry at the University of Bradford
He is a coauthor on several qualitative psychedelic-therapy papers that help characterize patient experience, insight, and therapeutic mechanisms in psilocybin and MDMA-assisted treatment.
Ignacio Carrera
Assistant Professor in Organic Chemistry at the Universidad de la República (Facultad de Química)
He is a Uruguayan chemist central to interdisciplinary psychedelic research in Uruguay, with publications on ayahuasca chemistry and ibogaine’s neuropharmacology.
Michael Mithoefer
Senior Medical Director for Medical Affairs at MAPS PBC
Conducted the first FDA-approved clinical trial of MDMA-assisted therapy for PTSD.
Michael Bogenschutz
Professor of Psychiatry
A leading clinician-researcher who has advanced the clinical development of psilocybin-assisted psychotherapy for alcohol use disorder and contributed foundational psychotherapeutic models and clinical trial methodology in modern psychedelic medicine.
Peter Hendricks
Professor of Health Behaviour and Psychedelic Research
Noted for rigorous population‑level epidemiological analyses elucidating associations between classic psychedelic use and mental and physical health outcomes, and for advancing research on microdosing and adverse psychological responses.
Luiz Tófoli
Professor in the Department of Psychiatry, Faculty of Medical Sciences, UNICAMP
Notable for empirical and methodological contributions to the study of ayahuasca, ibogaine and early-stage psychedelic-assisted therapies in Brazil, including survey research on adverse effects and pilot clinical work with MDMA-assisted psychotherapy.
Connected Evidence
The latest clinical data and verified academic findings associated with Tobacco/Nicotine Use Disorder (TUD).