25 mg or 2.5mg Is there anything psilocybin can’t do?

Single-dose psilocybin therapy shows promise for reducing alcohol consumption | Eric W. Dolan, PsyPost

A new study published in the Journal of Psychopharmacology suggests that a single high dose of psilocybin, combined with psychological support, can lead to reductions in alcohol use among people with severe alcohol use disorder. In this small open-label study, all participants completed the treatment, and most showed notable decreases in heavy drinking, alcohol cravings, and increased confidence in their ability to abstain. These effects were observed even though there were wide differences in how individuals processed the drug.

Psilocybin is a naturally occurring psychedelic compound found in certain species of mushrooms. It has gained increasing scientific interest in recent years for its potential to treat mental health conditions, including depression, anxiety, and substance use disorders. The compound affects serotonin receptors in the brain and can cause profound alterations in perception, self-awareness, and emotion. Most research exploring its therapeutic potential in alcohol use disorder has involved multiple doses, but the authors of this study wanted to know whether a single dose might also produce meaningful changes.

“I was intrigued by the early pilot studies on alcohol use disorder and nicotine dependence showing that just a few doses of psilocybin could have immediate and long-lasting effects,” explained study author Mathias Ebbesen Jensen, a postdoctoral researcher at the Neuropsychiatric Laboratory at Psychiatric Center Copenhagen.

“At that time, I did clinical research with GLP-1 receptor agonist for alcohol use disorder, which was a more traditional pharmacological approach. Psilocybin contrasted this in many ways by showing long-lasting benefits way beyond the drugs presence in the organism. I was also very inspired by the work of William Miller, who is perhaps best known for developing Motivational Interviewing, a counselling style widely used in addiction, who had this concept of sudden change he called quantum change.

“Quantum change contrasted the gradual change and was characterized by a sudden and spontaneous transformative experiences that would change one’s attitude and behavior in a benevolent and long-lasting way,” Jensen explained. “The phenomenology of quantum change experiences bear a striking resemblance with the psilocybin-induced experiences, and I thought, perhaps we can occasion quantum changes with psilocybin and thereby radically change their drinking behavior.”

The research team designed an open-label, single-group trial involving ten adults seeking treatment for alcohol use disorder. Eight men and two women participated, with a median age of 44 years. All had severe alcohol use disorder, as confirmed by diagnostic criteria and self-report questionnaires. Importantly, many of the participants had never received treatment before, and only half had prior experience with psychedelics.

The treatment protocol included five sessions: two preparatory therapy meetings before the psilocybin session, one high-dose psilocybin session (25 milligrams), and two integration sessions afterward. The therapy incorporated elements of motivational interviewing, acceptance and commitment therapy, and guided imagery. These approaches were chosen to help participants prepare for and reflect on the psychological effects of the psychedelic experience.

On dosing day, participants arrived at the clinic after a light meal and underwent medical screening. They ingested a capsule containing 25 milligrams of psilocybin and listened to a curated six-hour music program while reclining in a comfortable room with two trained therapists present. The therapists provided support but mostly kept interaction minimal unless participants needed reassurance or guidance. Subjective drug intensity was assessed every 20 minutes during the session. After the effects wore off, participants completed several questionnaires to assess the quality and emotional tone of the experience.

Blood samples were collected at multiple time points to measure the concentration of psilocin—the active form of psilocybin—in the bloodstream. These measurements allowed the researchers to track how quickly and how strongly each participant absorbed and metabolized the drug. The results showed substantial differences across participants, with peak blood concentrations ranging from 14 to 59 micrograms per liter, and times to reach peak levels ranging from just over an hour to nearly five hours.

Despite this variation, all participants reported intense psychedelic effects. Most achieved the highest possible subjective intensity score, and many described their experience using terms consistent with mystical-type experiences. These included feelings of unity, transcendence of time and space, and a deep sense of meaning. On average, the peak effects occurred around 1.3 hours after ingestion and lasted for approximately six hours.

All ten participants completed the full course of treatment. No serious side effects were reported. Mild and short-lasting side effects such as anxiety, headache, and fatigue were common in the first day but resolved without medical intervention. Blood pressure and heart rate increased slightly after dosing but remained within safe ranges. These findings suggest that the treatment was feasible and well-tolerated.

The researchers measured changes in drinking behavior using a well-established method that tracks alcohol use over time. Twelve weeks after the psilocybin session, participants had reduced their number of heavy drinking days by an average of 37.5 percentage points. The number of drinks consumed per day also dropped significantly, with a median reduction of about 3.4 drinks.

“This was the first study to assess the safety and efficacy of just a single psilocybin dose for patients with alcohol use disorder,” Jensen told PsyPost. “It was also the first study to assess blood samples during the psychedelic session to see how the blood concentrations of the drug behaved over time and whether this was important in relation to the effects. We found that a single dose of psilocybin with few psychotherapy sessions before and after was safe and significantly reduced heavy drinking for at least 12 weeks.”

Craving scores decreased markedly just one week after treatment and remained lower at weeks four and twelve. At the same time, participants reported feeling more confident in their ability to resist alcohol use, and this sense of self-efficacy remained elevated throughout the follow-up period.

Interestingly, the researchers found that participants who reported more intense mystical-type experiences during their psilocybin session were more likely to show sustained reductions in drinking. However, the actual concentration of psilocin in the blood was not linked to treatment outcomes. This suggests that the psychological nature of the experience, rather than the exact dose absorbed, may play a key role in promoting change. In particular, participants who met criteria for a “complete mystical experience” were more likely to be classified as treatment responders.

“In many ways, I was surprised that the total amount of drug exposure did not relate to a better treatment outcome e.g., the peak concentration of psilocin (the active metabolite of psilocybin) was not associated with efficacy,” Jensen said. “Participants with peak concentrations below the average, still had very profound and intense experiences that predicted a better treatment response.

“There is probably a threshold for entering a therapeutic altered state of consciousness, which is perhaps quite individual and depends on several non-pharmacological factors. We could speculate that a person who has personality traits of high openness to experiences and suggestibility would need a lower blood psilocin concentration than others. Obviously much more research is needed.”