Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study
Methodology: An early proof-of-concept study. This was a single-group open-label trial. All participants underwent a 12-week psychotherapy program incorporating Motivational Enhancement Therapy (MET) for alcohol use, with additional sessions for psilocybin preparation and integration. Each patient received one or two supervised psilocybin sessions (doses were described as one “moderate” and one “high” dose, exact amounts not in abstract).
Sample: 10 adults meeting DSM-IV criteria for alcohol dependence.
Dosage: For the first psilocybin session, participants received a dose of 0.3 mg/kg. For the second session, the dose was increased to 0.4 mg/kg unless the participant (i) was unwilling to increase the dose; (ii) experienced adverse effects during the first session which suggested that a higher dose would pose significant risk; or (iii) reported a “complete” mystical experience during the first session.
Key Findings:
– Alcohol abstinence did not improve during the initial 4 weeks of MET-only therapy (before psilocybin) but increased significantly following psilocybin administration.
– In the weeks after the first psilocybin session, participants greatly reduced drinking: the number of days abstinent from alcohol rose markedly (p < 0.05) compared to the pre-psilocybin baseline.
– These gains were largely maintained at 36-week follow-up, suggesting durability of benefit.
– Additionally, the intensity of the psychedelic experience (especially during the first psilocybin session at week 4) was strongly predictive of positive outcomes: participants who had more profound effects showed larger decreases in alcohol craving and consumption and greater increases in self-efficacy for abstinence in the ensuing weeks.
– Safety: No serious treatment-related adverse events were observed.
Implications:
This pilot provided preliminary evidence that psilocybin-assisted therapy can catalyze significant reductions in alcohol use in alcohol-dependent individuals, laying groundwork for controlled trials.
Citation: Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A., Wilcox, C. E., Barbosa, P. C., & Strassman, R. J. (2015). Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. Journal of psychopharmacology (Oxford, England), 29(3), 289–299. https://doi.org/10.1177/0269881114565144
Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder
Methodology: Double-blind RCT (Phase II). Participants were randomized to psilocybin vs. an active placebo. Both groups received a 12-week manualized psychotherapy program for alcohol cessation, which included motivational interviewing and cognitive-behavioral components, delivered by two therapists. Within this therapy framework, the psilocybin group received two psilocybin sessions (at weeks 4 and 8, approximately) while the control group received two sessions with an active placebo (50–100 mg of diphenhydramine, an antihistamine). Neither participants nor therapists knew which substance was administered in the dosing sessions. The therapy was delivered with careful safety monitoring; two therapists were present for sessions, and participants received thorough preparation, reflecting the controlled setting of the trial.
Sample: 95 adults with alcohol use disorder (mean ~46 years old; 42% female). Participants had a long history of alcohol misuse (averaging ~14 years dependent) and were drinking heavily at baseline (mean ~50–60% of days were heavy drinking days).
Dosage: Psilocybin was given at about 25 mg per 70 kg in session 1 and 40 mg/70 kg in session 2 (doses tailored to body weight). These are full psychedelic doses, expected to induce robust subjective effects.
Key Findings:
– The primary outcome was percentage of heavy drinking days (% HDD) during the 32-week post-treatment follow-up period.
– Results showed a significant improvement in drinking outcomes with psilocybin. Over 32 weeks, patients who received psilocybin + therapy had substantially fewer heavy drinking days than those given placebo + therapy. Specifically, the psilocybin group’s %HDD was ~9.7% versus ~23.6% in the control group (a ~14% absolute reduction). This difference was statistically significant (Hedges’ g ~0.5, p≈0.01)
– Psilocybin-treated patients were roughly 2–3 times more likely to remain completely abstinent in the last months of follow-up: by weeks 33–36, 48% of the psilocybin group had no alcohol use at all, compared to 24% of the placebo group.
– They were also more likely to avoid any heavy drinking (62.5% vs 40% with no heavy-drinking episodes in weeks 33–36, OR ~2.5).
– Both groups reduced their drinking-related problems over time, but the psilocybin group showed larger gains on several measures (for example, a greater percentage achieved a drop in WHO risk level for alcohol harm).
– These improvements emerged on top of the effects of psychotherapy – notably, even the placebo group (with therapy alone) reduced drinking to some extent, but psilocybin provided an additional boost.
– Psilocybin sessions transiently raised blood pressure and heart rate (expected acute effects) but did not cause severe medical or psychiatric events.
– No increase in adverse psychiatric events (like severe anxiety or psychosis) was observed under the controlled conditions.
Implications:
This trial provided the first placebo-controlled evidence that psilocybin-assisted therapy can produce “robust decreases” in alcohol misuse beyond psychotherapy alone. It expanded on the 2015 pilot’s findings and, with 93 completers, was the largest psilocybin trial in SUD published to date at that time. Researchers noted the need for further replication but were encouraged that psilocybin, paired with therapy, significantly improved abstinence rates and reduced relapse in individuals with AUD.
Citation: Bogenschutz, M. P., Ross, S., Bhatt, S., Baron, T., Forcehimes, A. A., Laska, E., Mennenga, S. E., O’Donnell, K., Owens, L. T., Podrebarac, S., Rotrosen, J., Tonigan, J. S., & Worth, L. (2022). Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder. JAMA Psychiatry, 79(10), 953. https://doi.org/10.1001/jamapsychiatry.2022.2096
Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction
Methodology: Open-label pilot trial (no control group). All participants received a 15-week smoking cessation treatment protocol consisting of weekly Cognitive Behavioral Therapy (CBT) for quitting smoking, and psilocybin administered on two to three occasions during the course of therapy. The first psilocybin session was timed to coincide with the target quit date (approximately week 5 of the program), with up to two additional sessions in subsequent weeks to reinforce abstinence. Extensive preparation and post-session counseling were provided.
Sample: 15 chronic cigarette smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake.
Dosage: About 20 mg/70 kg in the first session and 30 mg/70 kg in the second (and third, if given). These weight-adjusted doses (≈0.286 and 0.429 mg/kg) induce full psychedelic effects.
Key Findings:
– At 6 months after the target quit date, 80% of participants (12 out of 15) were confirmed to be abstinent from smoking, a success rate substantially higher than typical for smoking cessation (~30% or less with standard methods).
– A 12-month follow-up found that 67% (10/15) remained abstinent at 1 year, verified by biological measures (exhaled CO and cotinine levels).
– At an average of 2.5 years after quitting (30 months), 60% (9/15) of the original sample still had not returned to smoking.
– Moreover, the depth of the psilocybin experience appeared important: participants who achieved abstinence tended to report profound psychedelic effects. In fact, 86.7% rated at least one of their psilocybin sessions as among the top 5 most meaningful and spiritually significant events of their lives.
– Qualitative feedback indicated that the experience helped them reconceptualize themselves “as non-smokers” and break habitual patterns, supporting the idea that a transformative psychological experience contributed to quitting.
– No serious adverse events were noted in the published reports. Transient anxiety or psychological discomfort occurred during some sessions, but these were managed with therapist support.
Implications:
This pilot provided proof-of-concept that psilocybin combined with therapy could facilitate smoking cessation in hard-to-treat smokers. The abstinence rates were dramatically higher than any medication or CBT alone had achieved in similar populations. While the study was small and not randomized, it paved the way for larger trials. The researchers cautioned that expectancy effects or selection factors (participants highly motivated to try psychedelics) might have influenced results, but the magnitude of success suggested a real treatment signal. The long-term follow-up paper in 2017 concluded that psilocybin-assisted CBT “holds considerable promise in promoting long-term smoking abstinence,” calling for rigorous controlled trials.
Citation: Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., & Griffiths, R. R. (2014). Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of psychopharmacology (Oxford, England), 28(11), 983–992. https://doi.org/10.1177/0269881114548296