Single-dose psilocybin therapy shows promise for reducing alcohol consumption

OG article

June 17 2025

A recent study published in the Journal of Psychopharmacology provides compelling evidence that a single high dose of psilocybin, administered with psychological support, may significantly reduce alcohol consumption in individuals with severe alcohol use disorder (AUD). Conducted as a small-scale, open-label trial, the study demonstrated that all participants completed the treatment protocol, with the majority exhibiting substantial reductions in heavy drinking days, alcohol cravings, and enhanced confidence in maintaining abstinence. These outcomes persisted despite significant inter-individual variations in psilocybin metabolism.

Psilocybin, a naturally occurring psychedelic compound found in certain mushroom species, has garnered increasing scientific attention for its potential therapeutic applications in treating mental health conditions, including depression, anxiety, and substance use disorders. By interacting with serotonin receptors in the brain, psilocybin induces profound changes in perception, self-awareness, and emotional processing. While prior research on psilocybin for AUD has typically explored multi-dose protocols, this study sought to evaluate the efficacy of a single-dose approach.

Study author Mathias Ebbesen Jensen, a postdoctoral researcher at the Neuropsychiatric Laboratory at Psychiatric Center Copenhagen, explained, “Early pilot studies on AUD and nicotine dependence demonstrated that limited psilocybin doses could produce immediate and sustained effects. In contrast to conventional pharmacological treatments I had studied, such as GLP-1 receptor agonists for AUD, psilocybin’s long-lasting benefits persisted beyond its presence in the body. I was also inspired by William Miller’s concept of ‘quantum change,’ a sudden, transformative experience that reshapes attitudes and behaviors in a lasting, positive manner. The parallels between quantum change and psilocybin-induced experiences led me to hypothesize that psilocybin could facilitate such transformations in drinking behavior.”

The trial involved ten adults with severe AUD, comprising eight men and two women with a median age of 44 years. Confirmed by diagnostic criteria and self-reported questionnaires, all participants met the criteria for severe AUD, with many having no prior treatment history and only half reporting previous psychedelic use. The treatment protocol consisted of five sessions: two preparatory therapy sessions, a single high-dose psilocybin session (25 milligrams), and two post-session integration sessions. The therapeutic framework integrated motivational interviewing, acceptance and commitment therapy, and guided imagery to optimize participants’ preparation for and reflection on the psychedelic experience.

On the dosing day, participants underwent medical screening after a light meal and consumed a 25-milligram psilocybin capsule in a comfortable clinical setting, accompanied by a curated six-hour music program. Two trained therapists provided minimal interaction, offering support only as needed. Subjective drug intensity was assessed every 20 minutes, and post-session questionnaires evaluated the emotional and qualitative aspects of the experience. Blood samples, collected at multiple intervals, measured psilocin—the active metabolite of psilocybin—revealing significant variability in peak concentrations (14 to 59 micrograms per liter) and time to peak levels (1 to nearly 5 hours).

Despite this pharmacokinetic variability, all participants reported intense psychedelic effects, with most achieving the maximum subjective intensity score and describing mystical-type experiences characterized by unity, transcendence, and profound meaning. Peak effects occurred approximately 1.3 hours post-ingestion, lasting around six hours. No serious adverse effects were reported, with mild, transient side effects such as anxiety, headache, and fatigue resolving without intervention. Vital signs, including blood pressure and heart rate, showed slight increases but remained within safe limits, indicating the treatment’s safety and tolerability.

Using a validated timeline follow-back method, the researchers observed a 37.5 percentage-point reduction in heavy drinking days at 12 weeks post-treatment, alongside a median decrease of 3.4 drinks per day. Jensen noted, “This study is the first to evaluate the safety and efficacy of a single psilocybin dose for AUD, as well as the first to analyze blood psilocin levels during the session to explore their relationship to outcomes. Our findings confirm that a single dose, supported by minimal psychotherapy, is safe and significantly reduces heavy drinking for at least 12 weeks.”

Craving scores dropped significantly within one week and remained lower at weeks four and twelve, while participants’ confidence in resisting alcohol use increased and sustained throughout the follow-up period. Notably, those reporting more intense mystical-type experiences, particularly those meeting criteria for a “complete mystical experience,” were more likely to exhibit sustained reductions in drinking. However, blood psilocin concentrations showed no correlation with treatment outcomes, suggesting that the psychological quality of the experience, rather than drug exposure, drives therapeutic efficacy. Jensen remarked, “Surprisingly, peak psilocin levels did not predict better outcomes. Participants with below-average concentrations still reported profound experiences that correlated with improved treatment responses, indicating that a therapeutic altered state may depend on individual factors like openness to experience or suggestibility.”

The study’s limitations include its small sample size of ten participants, which restricts generalizability, and its open-label design, which introduces potential expectation bias. The absence of a control group limits attribution of outcomes to psilocybin versus psychotherapy or placebo effects. Additionally, conducted in Denmark with self-referred participants, the study may not fully represent the diversity of individuals with AUD. Jensen cautioned, “These results should be interpreted cautiously due to the small, predominantly male sample and lack of a control group, which likely amplified expectation effects. Larger, placebo-controlled trials are needed to validate these findings.”

The research team is advancing a randomized, placebo-controlled trial, set to conclude in fall 2025, to further investigate the single-dose approach. This study will incorporate neuroimaging and blood markers of neuroplasticity to explore psilocybin’s neurobiological effects. The study, titled “Single-dose psilocybin therapy for alcohol use disorder: Pharmacokinetics, feasibility, safety, and efficacy in an open-label study,” was authored by Mathias Ebbesen Jensen, Dea Siggaard Stenbæk, Catharina Dragsted Messell, Emil Deleuran Poulsen, Tibor V. Varga, Patrick McDonald Fisher, Marie Katrine Klose Nielsen, Sys Stybe Johansen, Nora D. Volkow, Gitte Moos Knudsen, and Anders Fink-Jensen.