This pilot randomised clinical trial (n=82) found that a single dose of psilocybin (30mg/70kg) combined with cognitive behavioural therapy produced significantly higher long-term smoking abstinence rates at 6 months compared to nicotine patches plus CBT (41% vs 10%), with no serious adverse events attributed to either treatment.
Papers cited by this study that are also in Blossom
Johnson, M. W. · Current Topics in Behavioral Neurosciences (2022)
Importance
Annual tobacco-related death estimates are 480 000 in the US and 8 million worldwide, surpassing mortality for other abused substances. Most smoking cessation interventions result in modest long-term success.
Objective
To compare prolonged smoking abstinence rates in smokers receiving psilocybin plus cognitive behavioral therapy (CBT) with those receiving the nicotine patch plus CBT.
Design, Setting, and Participants
In this pilot randomized clinical trial, participants and investigators were unblinded to treatment condition, including an optional crossover after completion of the primary end point. Data were collected from psychiatrically healthy adult smokers from January 20, 2015, to May 8, 2023, at the Johns Hopkins Bayview Medical Center, an academic medical center and teaching hospital in Baltimore, Maryland.
Intervention
The trial randomized cigarette smokers to receive either 1 high dose (30 mg/70 kg) of psilocybin or initiate 8 to 10 weeks of US Food and Drug Administration–approved nicotine patch treatment on the target quit date. Both groups received a 13-week manualized CBT program for smoking cessation.
Main Outcomes and Measures
Biochemically verified prolonged smoking abstinence (primary) and 7-day point prevalence abstinence (secondary) at 6 months after the target quit date were compared between groups using intention-to-treat analysis.
Results
A total of 82 psychiatrically healthy adult smokers (mean [SD] age, 47.6 [12.0] years; 49 [59.8%] male) participated in the study, with 68 (82.9%) completing the 6-month follow-up. At 6-month follow-up, 17 participants receiving psilocybin (40.5%) exhibited biochemically verified prolonged abstinence compared with 4 participants using the nicotine patch (10.0%) (odds ratio, 6.12; 95% CI, 1.99-23.26; P = .003), and 22 participants receiving psilocybin (52.4%) exhibited biochemically verified 7-day point prevalence abstinence compared with 10 participants using the nicotine patch (25.0%) (odds ratio, 3.30; 95% CI, 1.32-8.70; P = .01). No serious adverse events were attributed to psilocybin or nicotine patch.
Conclusions and Relevance
In this pilot randomized clinical trial, 1 dose of psilocybin with manualized CBT significantly increased long-term abstinence compared with nicotine patch treatment with CBT. Psilocybin abstinence rates were higher than typical treatments, suggesting promise for tobacco smoking cessation.
Smoking is a leading cause of premature death worldwide, causing roughly 8 million deaths annually and about 480 000 in the US. Existing cessation treatments (varenicline, bupropion, nicotine replacement therapy, and counselling) outperform placebo but commonly fail within six months, leaving a large unmet need. Classic serotonergic (5-HT2A) psychedelics have shown preliminary therapeutic promise across psychiatric conditions, including addictions. Earlier work, including an open-label pilot by some of the current authors, reported high biologically verified abstinence rates following manualised cognitive behavioural therapy (CBT) combined with up to three psilocybin administrations for tobacco cessation, and epidemiological and naturalistic data have suggested associations between psychedelic use and reduced tobacco use. Johnson and colleagues designed a randomised clinical trial to compare a single dose of psilocybin (30 mg/70 kg) plus manualised CBT with a standard, FDA‑labelled nicotine patch regimen plus the same CBT. Nicotine patch was chosen as the active comparator because of its well-characterised safety and efficacy profile in smoking cessation. The trial aimed to evaluate whether psilocybin-assisted therapy could produce superior biologically verified smoking abstinence at clinically meaningful follow-up intervals, with 6-month prolonged abstinence prespecified as the primary outcome.
This pilot randomised comparative efficacy trial screened 152 individuals and randomised a final analytic sample of 82 participants; 70 were disqualified or declined participation. The study was approved by an institutional review board and followed CONSORT guidance; participants provided written informed consent. Sample size decisions were driven by available funding rather than statistical power calculations, with targets increased over time as funding permitted; a subsample underwent fMRI (results not reported here). Demographic data including self-reported race and ethnicity were collected using US Census categories. The intervention structure comprised four preparatory CBT visits with a target quit date in week 5, when treatment was initiated. Participants randomised to the psilocybin arm received psychoeducation during preparatory visits and a single supervised psilocybin dose of 30 mg/70 kg at the target quit visit, followed by a debrief the next day and ongoing integration/support sessions (weekly through week 7, then biweekly through week 13). During dosing participants reclined, used eyeshades, were encouraged to focus inward and listened to music. Participants randomised to the nicotine patch arm received standardised psychoeducation and began an 8–10 week nicotine patch regimen per FDA labelling (dose adjusted by baseline cigarettes per day), with the same schedule of counselling visits. Two facilitators who were aware of treatment assignments delivered the interventions. To reduce differential dropout, nicotine patch participants were offered a single crossover psilocybin administration after completing the 6‑month primary end point. Biological verification of smoking abstinence used exhaled carbon monoxide (CO) and urinary cotinine, assessed at intake and at 3, 6 and 12 months; CO was also measured at multiple interim visits. Self-report measures included a timeline follow-back (TLFB) calendar of daily cigarettes, the Fagerström Test for Cigarette Dependence (FTCD), the Contemplation Ladder (readiness to quit), and the Questionnaire on Smoking Urges. Adverse events (AEs) were captured at study visits by open inquiry and judged related or unrelated to the intervention based on timing, participant attribution, and investigator assessment. The prespecified primary outcome was prolonged smoking abstinence at 6 months, defined as no smoking following a 14-day grace period after the target quit date. A priori secondary outcomes included 7‑day point prevalence abstinence (no smoking in the 7 days prior to a visit) and mean post‑target quit date cigarettes per day (CPD). Abstinence determinations combined CO (≤5 ppm), cotinine (<200 ng/mL), and TLFB; when biochemical and self-report conflicted due to noncombustible nicotine use, participants were coded as abstinent only if TLFB and CO both indicated no smoking. An additional analysis treated any noncombustible nicotine product use or positive cotinine as nonabstinent. Analyses used an intention‑to‑treat approach: all randomised participants were included and those lost to follow-up or who discontinued were counted as nonabstinent. Statistical tests used R and GraphPad Prism. Between‑group abstinence rates were analysed using binary logistic regression without covariates (groups were highly comparable at baseline). An exploratory analysis of daily cigarette use from target quit date to 6 months employed generalised linear mixed‑effects models for overdispersed count data, with participant random intercepts and baseline CPD as a covariate; this analysis was restricted to participants who provided TLFB data through 6 months (n = 68). No data imputation was performed.
In this pilot randomized clinical trial with a comparative efficacy design, 152 individuals were screened and 70 were disqualified for not meeting criteria (n = 64) or declining participation (n = 6), resulting in a final analytic sample of 82 participants (Figure). To characterize sample demographics, we collected self-reported data on participant race and ethnicity via a survey querying US Census racial categories: White, Black or African American, American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander, with the addition of "some other race" and "more than one race." Ethnicity data were collected via the survey question, "Do you identify as Hispanic or Latino?" Sample size was informed by financial rather than statistical considerations because of limited data on effect size from prior research. The study initially targeted a total sample of 30, increasing later to targeted samples of 50, 80, and 100 as more funding became available and to support functional magnetic resonance imaging (fMRI) data validity (not reported here). The sample size of 82 reflects what was viable to complete with the available funding support. See eAppendix 1 in Supplement 1 for supplementary information. This study was approved by an institutional review board at Johns Hopkins University School of Medicine and followed the 1964 Declaration of Helsinki.Participants provided written informed consent. There was no formal patient or public involvement in the design, conduct, and reporting of the trial. This report follows the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline for randomized trials.The trial protocol can be found in Supplement 2. In the first 4 treatment visits, participants underwent CBT with a target quit date set in week 5. In week 5, one group received 30 mg/70 kg of psilocybin and the other received a course of nicotine patches (Figure). Two facilitators who were aware of treatment assignments (a doctoral/master'slevel psychologist [A.G.R.] and a research coordinator with a bachelor's degree or higher level in mental health) delivered the intervention. All participants were contacted daily via telephone (<5 minutes) or text message in the week after the target quit date to encourage smoking abstinence. Participants had weekly visits with facilitators across weeks 1 to 7 and at 2-week intervals across weeks 9 to 13, with follow-up visits 3, 6, and 12 months after the target quit date. Study visits were in-person until March 2020, when most study visits became virtual due to COVID-19, except psilocybin administration, 3-to 12-month follow-up visits, and nicotine patch pick-up visits. To reduce differential dropout, we gave participants randomized to the nicotine patch group the option of a single crossover psilocybin administration after completing the 6-month follow-up (primary end point). A subsample of participants underwent fMRI before and after treatment. Results from the 12-month follow-up, crossover, and fMRI and potential mechanisms will be published separately.
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Krebs, T. S., Johansen, P. Ø. · Journal of Psychopharmacology (2012)
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. et al. · Journal of Psychopharmacology (2014)
Johnson, M. W., Garcia-Romeu, A., Griffiths, R. R. · The American Journal of Drug and Alcohol Abuse (2016)
Jones, G. M., Lipson, J., Nock, M. K. · Scientific Reports (2022)
Johnson, M. W., Garcia-Romeu, A., Johnson, P. S. et al. · Journal of Psychopharmacology (2017)
Nayak, S., Bradley, M. K., Kleykamp, B. A. et al. · Journal of Clinical Psychiatry (2023)
Simonsson, O., Sexton, J. D., Hendricks, P. S. · Journal of Psychopharmacology (2021)
Johnson, M. W., Richards, W. A., Griffiths, R. R. · Journal of Psychopharmacology (2008)
Bogenschutz, M. P., Johnson, M. W. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2016)
Garcia-Romeu, A., Davis, A. K., Griffiths, R. R. et al. · Frontiers in Psychiatry (2020)
Noorani, T., Garcia-Romeu, A., Swift, T. C. et al. · Journal of Psychopharmacology (2018)
Murphy-Beiner, A., Soar, K. · Psychopharmacology (2020)
Sloshower, J. A., Zeifman, R. J., Guss, J. et al. · Scientific Reports (2024)
Griffiths, R. R., Johnson, M. W. · Journal of Psychopharmacology (2016)
Doss, M. K., Považan, M., Rosenberg, M. D. et al. · Translational Psychiatry (2021)
Szigeti, B., Weiss, B., Rosas, F. E. et al. · Psychological Medicine (2024)
Goodwin, G. M. · Journal of Affective Disorders (2023)
Goodwin, G. M., Malievskaia, E., Fonzo, G. A. et al. · American Journal of Psychiatry (2023)
Papers in Blossom that reference this study
Hendricks, P. S., Lappan, S. N., Shelton, R. C. et al. · JAMA Network Open (2026)
The trial randomised 82 participants after screening 152 individuals. Retention counts reported in the extracted text were 76 participants at week 2, 75 at week 4, 74 at weeks 6 and 8, 74 at week 13, and 68 at week 26; however, intention‑to‑treat analyses counted missing time points as nonabstinent. On the day after the target quit date, 38 participants in the psilocybin group were abstinent compared with 10 participants (25.0%) in the nicotine patch group (as reported in the extracted text). At the prespecified 6‑month primary end point, the psilocybin group showed substantially greater abstinence: logistic regression estimated odds of prolonged abstinence were greater in the psilocybin arm (OR 6.12; 95% CI 1.99–23.26; P = .003). For 7‑day point prevalence abstinence, the psilocybin group also had higher odds (OR 3.30; 95% CI 1.32–8.70; P = .01). The exploratory mixed‑effects analysis of daily cigarette use between the target quit date and 6 months indicated a strong treatment effect favouring psilocybin (incidence rate ratio 0.04; 95% CI 0.004–0.27; P = .002), with model predictions showing lower CPD in the psilocybin group. A zero‑inflated model provided a substantially better fit, consistent with a distinct abstinence‑related process. Model‑predicted CPD were 1.69 (95% CI 1.63–1.75) for the psilocybin group and 3.64 (95% CI 3.56–3.73) for the nicotine patch group, a 53.7% difference; observed mean (SD) CPD were 1.79 (3.32) and 3.73 (4.18), respectively. Exploratory analyses reported that prior lifetime psychedelic use (reported by 53 participants, 64.6%) did not significantly modify prolonged abstinence outcomes. Regarding safety, no serious study‑related adverse events were reported. Seventy participants (85.4%) reported at least one adverse event during the study (the extracted text truncates further detail). The authors characterised study‑related AEs as clinically nonsignificant and largely expected psilocybin effects (for example, transiently increased blood pressure, headache, and nausea) that were well managed during supervised sessions.
Johnson and colleagues interpret their findings as showing that a single supervised psilocybin administration combined with manualised CBT produced greater smoking abstinence than a standard nicotine patch regimen combined with the same CBT. At 6 months, psilocybin was associated with more than sixfold greater odds of prolonged abstinence (the primary outcome) and more than threefold greater odds of 7‑day point prevalence abstinence (a secondary outcome). Participants randomised to psilocybin smoked approximately 50% fewer cigarettes per day on average in the period from the target quit date to 6 months. The authors report no serious AEs attributable to psilocybin and describe the observed AEs as clinically nonsignificant, transient, and consistent with established psilocybin safety guidelines. The authors position these results within existing literature by noting that the nicotine patch group's abstinence rates were in line with prior NRT meta‑analytic results (the extracted text cites typical 6‑month prolonged abstinence of ~8% and 7‑day point prevalence ~20%), supporting the credibility of the comparator. They emphasise that psilocybin does not act directly on nicotinic acetylcholine receptors and therefore may operate via higher‑order psychological processes—such as changes in self‑concept and increased psychological flexibility—rather than by directly modifying drug reinforcement or withdrawal. The authors suggest that such psychological effects likely have accompanying biological correlates, though of a different and potentially more complex nature than those of traditional pharmacotherapies. The paper acknowledges several important limitations. The trial was nonblinded, raising the possibility that expectancy effects contributed to outcomes; the authors argue that functional blinding is rarely preserved in psychedelic trials and that an unblinded comparative efficacy design is appropriate for assessing outcomes in this context. Generalisability is limited: the sample had low ethnoracial diversity, was highly educated with high measured intelligence, and had a high prevalence of prior psychedelic use (64.6% v. ~13.8% in recent national data), suggesting potential recruitment bias and possible hesitancy among psychedelic‑naïve individuals to engage in such treatments. Although exploratory analyses indicated that prior psychedelic use did not mediate prolonged abstinence, the authors note this high prior‑use rate may limit external validity. Finally, because both arms received CBT, the trial cannot disentangle the independent contribution of psychotherapy from the pharmacological intervention. The authors recommend larger, ideally blinded trials to improve precision and generalisability of effect estimates.
In this pilot randomised clinical trial, a single supervised dose of psilocybin administered with manualised CBT produced significantly greater long‑term smoking abstinence than a standard nicotine patch regimen with the same CBT. The authors conclude that psilocybin is a promising candidate treatment for smoking cessation and suggest advancing it through the FDA process toward potential approval.
The participants randomized to the psilocybin group received psychoeducation regarding psilocybin effects during treatment visits 3 and 4 and were administered 30 mg/70 kg of psilocybin at visit 5 (target quit date). The next day, participants attended a debriefing visit with facilitators and met weekly through week 7 and every 2 weeks from weeks 9 to 13 to discuss the psilocybin experience and support smoking abstinence. During preparatory visits, participants were encouraged to view the psilocybin experience as an opportunity for reflection about the role of smoking in their lives and to enhance quitting motivation. During psilocybin dosing, participants typically lay on a couch wearing eyeshades, were asked to focus attention inward, and listened to a music program through headphones. The participants randomized to the nicotine patch group received standardized psychoeducation, including use instructions and potential AE information. In week 5, these participants began an 8-to 10-week regimen per FDA labeling (>10 cigarettes per day [CPD] smokers received 21 mg/d on weeks 1-6, 14 mg/d on weeks 7-8, and 7 mg/d on weeks 9-10; Յ10 CPD smokers received 14 mg/d on weeks 1-6 and 7 mg/d on weeks 7-8). Like the psilocybin group, participants had counseling visits weekly through week 7 and biweekly in weeks 9 to 13 to discuss treatment and support smoking abstinence.
Exhaled breath carbon monoxide detected smoking in the past day, and urinary cotinine detected smoking in the past week.Both were assessed at intake and at the 3-, 6-, and 12-month follow-up visits. Carbon monoxide was also assessed at all visits (in weeks 1-7, 9, 11, and 13). Carbon monoxide was assessed using a breath carbon monoxide monitor (Micro Smokerlyzer, Bedfont Scientific Ltd) at
A timeline follow-back (TLFB), retrospective, self-report calendar indicating the number of cigarettes smoked each day was completed at each study visit.The TLFB has shown good validity and reliability as a measure of daily smoking.The FTCD, 22 a 6-item questionnaire characterizing dependence severity, the Contemplation Ladder assessing readiness to quit smoking on a 0-to 10-point scale,and the Questionnaire on Smoking Urges 28 assessing smoking craving were completed at intake.
From the target quit date through the final follow-up, AEs were assessed by asking participants, "How have you been feeling since your last visit?" Staff recorded any new or worsening physical and mental health events self-reported or observed during study visits. AEs were deemed related or unrelated to the study intervention based on temporal proximity, participant attribution, and investigators' judgment.
The a priori primary study outcome was prolonged smoking abstinence at 6-month follow-up, with 7-day point prevalence abstinence and mean post-target quit date CPD as a priori secondary outcomes. Prolonged abstinence was defined as no smoking following an initial 14-day grace period after the target quit date.Seven-day point prevalence abstinence was defined as no self-reported smoking (not even a puff) in the 7 days preceding a visit. For both outcomes, abstinence was determined using carbon monoxide, cotinine, and TLFB. A carbon monoxide level of 5 ppm or less and cotinine levels of less than 200 ng/mL indicated nonsmoking.In cases where these conflicted due to reported use of other noncombustible nicotine products, participants were coded as smoking abstinent if TLFB and CO both indicated no smoking. Additional analyses counted any noncombustible nicotine product use or positive cotinine as nonabstinent, assessing potential impact on treatment outcomes (eAppendix 1 in Supplement 1). Those randomized to a group were counted as part of that group's abstinence rates regardless of receiving the intervention.
Data were collected from January 20, 2015, to May 8, 2023. Intention-to-treat analysis included all randomized participants; those who discontinued treatment or were lost to follow-up were counted as nonabstinent. Statistical tests were performed using R statistical software, version 4.4.1 (R Foundation for Statistical Computing)and GraphPad Prism, version 10.4.0 (GraphPad Software). Intake demographic and clinical characteristics were evaluated for normality using Shapiro-Wilk tests (where appropriate) and compared between groups using Welch t tests, Mann-Whitney U tests, or Fisher exact tests. Prolonged and 7-day point prevalence abstinence rates between groups were analyzed using binary logistic regression. These models contained no covariates due to highly comparable group baseline characteristics. Odds ratios (ORs) are reported with 95% CIs. Daily cigarette use between the target quit date and 6-month follow-up was evaluated as part of an exploratory analysis using generalized linear mixed-effects models suitable for count data with overdispersion. The models were fit to daily smoking data, with a random intercept for participant to account for correlation among repeated within-participant observations. Treatment group was included as the primary fixed effect, and baseline CPD was included as a covariate to adjust for pretreatment smoking levels. Analyses were restricted to participants who provided TLFB data extending at least through the 6-month follow-up period (n = 68) to ensure coverage of the full analysis window. No data were imputed. The outcome, based on the TLFB, was modeled as a rate
No serious study-related AEs occurred. A total of 70 participants (85.4%) reported an AE during the study (
On the day after the target quit date, 38 abstinence compared with 10 participants (25.0%) using the nicotine patch (Figure). At 6 months, logistic regression indicated that the psilocybin group had more than 6 times greater odds of prolonged abstinence (OR, 6.12; 95% CI, 1.99-23.26; P = .003) and more than 3 times greater odds of 7-day point prevalence abstinence (OR, 3.30; 95% CI, 1.32-8.70; P = .01). Generalized linear mixedeffects models of daily cigarette use between the target quit date and 6-month follow-up, conducted as an exploratory analysis, indicated a significant treatment effect (incidence rate ratio, 0.04; 95% CI, 0.004-0.27; P = .002), with lower model-predicted use in the psilocybin group. A zero-inflated model provided better fit (Akaike Information Criterion change, 4387; χ 2 1 = 4389; P < .001), supporting a distinct abstinence-related process. Model-predicted CPD was 1.69 (95% CI, 1.63-1.75) for psilocybin and 3.64 (95% CI, 3.56-3.73) for nicotine patch, reflecting a 53.7% difference between groups. Model-predicted and mean (SD) observed values (1.79 [3.32] in the psilocybin group and 3.73 [4.18] in the nicotine patch group) were closely aligned. Full model results are reported in eAppendix 1 in Supplement 1. Additionally, 53 participants (64.6%) reported prior psychedelic use, which is far higher than recent nationally representative data exhibiting a prevalence of 13.8%.Exploratory analysis suggested prolonged abstinence did not differ based on prior lifetime psychedelic use (eAppendix 1 in Supplement 1).
A single psilocybin dose combined with manualized CBT yielded significantly greater smoking abstinence than the nicotine patch paired with the same CBT. At 6 months, the psilocybin group had more than 6 times greater odds of showing prolonged abstinence (primary outcome) and more than 3 times greater odds of showing 7-day point prevalence abstinence (secondary outcome). Participants in the psilocybin group smoked a mean of approximately 50% fewer CPD between the target quit date and 6-month follow-up. Psilocybin appeared safe using established guidelines,with no serious AEs. Study-related AEs were clinically nonsignificant, well-managed, and largely expected psilocybin effects, such as transiently increased blood pressure, headache, and nausea. Psychedelic therapy requires few administrations, largely limiting AEs to supervised sessions. In contrast, typical smoking cessation medications are used daily for multiple weeks,resulting in potential for delayed AEs and adherence issues.A. Prolonged abstinence, which allowed for an initial 2-week grace period. B. Seven-day point prevalence abstinence in the week preceding each study visit. The number of individuals who completed each time point was 76 at week 2, 75 at week 4, 74 at week 6, 74 at week 8, 74 at week 13, and 68 at week 26. However, consistent with intention-to-treat analysis, all proportions reported here are based on the total randomized sample (N = 82), and those who did not complete a given time point were counted nonabstinent. The nicotine patch group showed abstinence rates consistent with the literature.A recent meta-analysisfound that standalone NRT resulted in 6-month prolonged abstinence rates of approximately 8% and 7-day point prevalence abstinence rates of 20%. The current study found a 10% prolonged abstinence rate and a 25% 7-day point prevalence abstinence rate, suggesting comparison condition credibility. Whereas nicotine patches confer an estimated OR of 1.37 compared with placebo for achieving smoking abstinence,in this study the psilocybin group had an OR of 6.1 for 6-month prolonged abstinence compared with nicotine patch participants, although these results require further validation due to the small sample size. The results of this study add to the increasing evidence that psychedelic treatment may have general antiaddiction efficacy across various addictive drugs.Psilocybin's lack of direct interaction with nicotinic acetylcholine receptors (or receptors mediating the effects of other addictive drugs) highlights psychedelic therapy as a unique approach wherein the pharmacotherapy does not directly alter drug reinforcement or withdrawal but may instead act via higher-order psychological systems, such as changes in self-conceptand enhanced psychological flexibility.Such mechanisms may also account for transdiagnostic benefits of psychedelic therapies (eg, for depression and anxiety).These psychological changes are likely associated with corresponding biological processes, just as there are presumably biological changes associated with successful psychotherapy. However, these biological processes are probably of a different nature and more difficult to characterize than those of traditional pharmacotherapies.
This study has several limitations. In this nonblinded study, expectancy could have contributed to positive outcomes. One study found that expectancy predicted antidepressant response to escitalopram but not psilocybin.We judged this unblinded comparative efficacy design, the reference standard for psychotherapy research, to be the best approach to assessing outcomes based on research showing extremely poor blinding integrity across double-blind psychedelic trials.One double-blind study of psilocybin for alcohol dependence found that 94% to 95% of participants correctly guessed treatment assignment.Other psilocybin studieshave used low-dose psilocybin or other drugs as comparators, although the success of these in maintaining functional blinding has not been demonstrated. Future double-blind studies in larger samples could help improve precision in estimated generalizable outcomes. Another limitation is sample generalizability. The sample was low in ethnoracial diversity. Moreover, the sample was highly educated with high intelligence, which could result in greater success, although the 2 groups were well matched on these characteristics, suggesting they did not contribute to differential efficacy. The relatively high level of study retention (>82% overall) suggests a highly motivated sample interested in psychedelic treatment, although it may also reflect clinical interest and feasibility of psychedelic treatments. Additionally, 64.6% of participants reported prior psychedelic use, far higher than recent nationally representative data exhibiting a prevalence of 13.8%.This finding suggests potential recruitment bias and nongeneralizability. However, exploratory results indicated efficacy was unrelated to prior psychedelic use. Nonetheless, the high rates of prior psychedelic use may indicate hesitancy among individuals without such history to engage in psychedelic-assisted therapies, possibly limiting uptake and use of these treatments. Because both groups received CBT, this study could not inform the contribution or necessity of psychotherapy.
In this pilot randomized clinical trial, administration of 1 dose of psilocybin with manualized CBT compared with nicotine patch treatment with CBT significantly increased long-term abstinence. The current trial's results suggest that psilocybin is a promising candidate for smoking cessation that should move forward in the FDA process toward potential approval.