• Currently, approved medications for alcohol dependence or alcohol use disorder are modestly effective, and there is a need for novel, more effective drugs.
• A small randomized clinical trial shows that administration of the psychedelic drug psilocybin in combination with psychotherapy reduced heavy drinking days in individuals with alcohol use disorder.
• Two doses of psilocybin given 4 weeks apart resulted in a sustained decrease in drinking that lasted at least 28 weeks after the last dose.
• Psilocybin thus holds promise for the treatment of alcohol use disorder, but further research is needed to determine the durability of its effects and the appropriate dosage.

A recent study published in JAMA Psychiatry has shown that psilocybin therapy, in addition to psychotherapy, reduced the number of heavy drinking days and average daily alcohol consumption in individuals with alcohol use disorder compared with an antihistamine placebo and psychotherapy.

This is the first randomized clinical trial (RCT) to show that psilocybin could help reduce excessive drinking in individuals with alcohol use disorder.

“Our findings strongly suggest that psilocybin therapy is a promising means of treating alcohol use disorder, a complex disease that has proven notoriously difficult to manage,” said study author, Dr. Michael Bogenschutz, director of New York University’s Langone Center for Psychedelic Medicine, in a news release.

Dr. Jennifer Mitchell, a neurology professor at the University of California, San Francisco, who was not involved in the study, told Medical News Today:

“We are in serious need of new therapeutics for alcohol use disorder, and one could imagine that a compound that successfully curbs alcohol consumption and depression might also prove effective for related mental health indications.”

Treating substance use disorders

Substance use disorder (SUD) is a condition characterized by the persistent use of a substance that impairs daily functioning, including causing health issues and interfering with major responsibilities. A substance use disorder is a mental health disorder, and individuals with a substance use disorder are unable to control the use of the substance.

Alcohol use disorder (AUD) is one of the most common SUDs, affecting around one-third of adults in the United States at some point during their lives.

Although there are medications available to treat AUD, about half of the individuals with the disorder tend to relapse within 6–12 months of treatment.

Moreover, these medications are only modestly effective, and many individuals do not respond to the medicines. As a result, there has been growing interest in using novel approaches to treat alcohol use disorder, including psychedelic substances.

Psychedelics show promise

Psychedelic compounds are substances that alter the state of consciousness, including mood, thought, perception, and sense of self.

Psychedelic substances were used to treat mental disorders, including SUDs, in the 1950s and 1960s. However, the classification of these substances as Schedule I drugs has stymied research on the therapeutic use of psychedelic substances.

Over the past two decades, there has been a resurgence of interest in the potential of psychedelic drugs for treating mood disorders and substance use disorders. One such psychedelic substance that has shown promise in treating substance use disorder is psilocybin, the active ingredient in magic mushrooms.

Psilocybin is considered a psychedelic, which is a class of drugs that produce hallucinations and other mind-altering effects once ingested. Specifically, psilocybin is thought to work by acting on serotonin 2A receptors in the brain.

Research from 2021 shows that psilocybin can improve mood and increase open-mindedness and willingness to change behaviors, suggesting that psilocybin could help overcome compulsive behaviors associated with SUDs.

Similar to the approach of using antidepressants along with psychotherapy for the treatment of depression, researchers have used psychedelic substances in addition to psychotherapy for the treatment of difficult-to-treat mental health conditions.

Psychedelic-assisted psychotherapy

Although the precise mechanism of psychedelic-assisted psychotherapy is unknown, researchers believe that psychedelic substances increase plasticity in the brain, and the increased flexibility conferred by psychedelic substances could enhance the effectiveness of psychotherapy.

“It is widely believed that although psilocybin can help the brain to change, it doesn’t necessarily determine the direction of that change,” explained Dr. Bogenschutz.

“So the drug prepares the person to change, and the therapy helps them to make the changes that they want to make, such as stopping or cutting down on their drinking in this case. So this could help explain why a single drug like psilocybin can help so many different conditions,” he continued.

Such psychedelic-assisted psychotherapy involves the administration of the psychedelic substance under the supervision of trained medical professionals.

Although previous research suggests that the frequency of serious adverse events after the administration of psychedelics like psilocybin is very low, using these drugs in a controlled environment can help effectively manage potential side effects.

As Dr. Bogenschutz and his colleagues had previously shown in a preliminary proof-of-concept study in 2015, psilocybin could reduce alcohol consumption in individuals with AUD. Building on these results, Dr. Bogenschutz recently conducted a randomized clinical trial to further assess the ability of psilocybin-assisted psychotherapy to reduce drinking behavior in individuals with alcohol use disorder.

Effects of psilocybin-assisted therapy

The present study consisted of 95 participants with alcohol use disorder who were randomized to receive either psilocybin or the antihistamine diphenhydramine. The study lasted 36 weeks, and the participants were administered a dose of either psilocybin or diphenhydramine at 4 and 8 weeks after the onset of the study.

The participants were also offered 12 weeks of motivational and cognitive behavioral therapy (CBT), with 4 weekly sessions before the first dose, between the first and the second dose, and after the second dose.

To assess the efficacy of psilocybin treatment, the researchers examined the number of heavy drinking days over the 32 weeks after administering the first dose of psilocybin or diphenhydramine at 4 weeks. A heavy drinking day was defined as 5 drinks a day for male participants and 4 drinks for female participants.

Participants receiving psilocybin had a lower percentage of heavy drinking days (9.7%) during the 32 weeks after the first dose than their counterparts in the diphenhydramine group (23.6%).

The percentage of participants who had no heavy drinking days after receiving the first dose was also higher in the psilocybin group than in the diphenhydramine group. Furthermore, the psilocybin group showed lower average daily consumption of alcohol than their peers in the diphenhydramine group.

Although mild side effects such as headaches, anxiety, and nausea were more prevalent in individuals receiving psilocybin than diphenhydramine, these side effects generally resolved on their own.

Notably, serious adverse events were absent in participants receiving psilocybin.

Limitations

The authors cautioned that the study had a few shortcomings. For instance, the participants could guess whether they had received psilocybin, which could have resulted in placebo effects.

The participants included in the study had moderate alcohol use disorder, and these results may not be generalizable to individuals with more severe alcohol use disorder.

Moreover, the researchers only monitored the participants for 32 weeks after the first dose, and long-term studies are needed to investigate the ability of psychedelic drugs to prevent relapse.

Additional research is needed before psilocybin can be used in a clinical setting. In an editorial accompanying the article, Dr. Henry Kranzler, professor of psychiatry at the University of Pennsylvania, noted:

“An important question is the extent to which a hallucinogenic experience is required for psychedelic drugs to have a therapeutic effect, which has implications for both the appropriate dosage and frequency of administration in the large-scale trials that will be needed for FDA approval. This question is also key to developing novel agents to target the mechanisms of therapeutic effects specific to different psychiatric disorders.”

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