Psychedelic Cuts Cravings, Consumption in Alcohol Use Disorder

Pauline Anderson

May 23, 2019

SAN FRANCISCO — Just two doses of the psychedelic drug psilocybin, taken over a period of 8 weeks, significantly reduced alcohol use and cravings in patients with alcohol use disorder, preliminary findings show.

In the first study to use modern clinical trial design to investigate the effects of a hallucinogen in alcohol-dependent patients, investigators at New York University (NYU) School of Medicine in New York City found that use of psilocybin was significantly associated with fewer drinking days and fewer drinks per day, as well fewer cravings.

Dr Kelley Clark O'Donnell

"Psychedelic research has the power, if performed in a rigorous way, to really change the face of psychiatry," study investigator Kelley Clark O'Donnell, MD, PhD, a resident in the Department of Psychiatry at NYU School of Medicine, told Medscape Medical News

However, she added, the risks of psychedelic drugs "should not be underestimated."

The findings were presented here at the American Psychiatric Association (APA) 2019 annual meeting.

Growing Interest in Hallucinogens

These findings contribute to a growing body of research into the use of psychedelic drugs for the treatment of psychiatric conditions.

The multisite, double-blind, randomized controlled trial assessed the effects of psilocybin-assisted psychotherapy on 180 alcohol-dependent patients. Alcohol dependence was determined on the basis of DSM-IV criteria.

Psilocybin is a naturally occurring serotonergic hallucinogen. As with lysergic acid diethylamide (LSD), another psychedelic drug, it is a 5HT2A receptor agonist.

Psilocybin is among the most studied psychedelic drugs. One of the reasons the investigators chose it for the current study is that its duration of action (about 6 to 8 hours) enables treatment to be conducted on an outpatient basis, said O'Donnell.

In contrast, LSD's duration of action can be up to 12 hours, which would necessitate an overnight hospital stay.

Participants were randomly assigned to receive psilocybin 24–40 mg/70 kg or the antihistamine diphenhydramine 50–100 mg in two dosing sessions.

Diphenhydramine (multiple brands) was chosen as the control drug because it has no effect on addiction but still might "make people feel a little woozy," said O'Donnell.

All patients received two types of psychotherapy. One combined motivational interviewing and cognitive-behavioral therapy. The other was specific to the psychedelic experience and involved "talking about the things patients might expect and doing a life review," said O'Donnell.

Patients received the medication at week 4 and at week 8 and attended therapy sessions in between doses — "so two doses a month apart," said O'Donnell.

Patients completed the Mystical Experience Questionnaire (MEQ) 8 hours after each medication session. The MEQ "is a measure of how intense the medication session was," said O'Donnell.

Life-Changer?

O'Donnell presented preliminary results from 56 participants (32 men and 24 women) who had completed the first 12 weeks of trial. The mean age of the participants was 46.0 years (range, 25.0 – 65.0 years); the mean education level was 16.9 years.

The mean number of drinks per day was 5.0 (range, 0.8 – 15.9). The participants' mean percent drinking days was 75.5. The mean number of drinks per drinking day was 7.5.

Because the study is ongoing, the researchers had to maintain the blindedness of the study. For the preliminary analysis, researchers divided the patients into two groups, high-MEQ and low-MEQ, on the basis of median MEQ score. (The median MEQ score was 0.26, and the mean MEQ score was 0.354).

There was no difference in daily alcohol consumption between high-MEQ and low-MEQ groups at baseline and immediately before the first medication session.

However, at week 12, a month after the participants had taken the second medication, alcohol use was significantly reduced in the high-MEQ group compared to the low-MEQ group (P < .05).

Among participants in the high-MEQ group, the percentage of drinking days was significantly lower compared to the low-MEQ group (18.73 vs 40.47; P < .05), and the number of drinks per drinking day was less (2.63 vs 7.01; P < .01).

The high-MEQ group reported significantly lower alcohol cravings (P < .01). There was no significant difference between the groups on measures of depression or anxiety.

Regarding the question as to whether the study would be truly blinded if participants who take psilocybin have a mystical experience, O'Donnell said: "We would expect that if you feel nothing, then probably you did not get psilocybin, and if you had a huge experience, then probably you did. So although the study is technically blinded, there are going to be people for whom the study is essentially unblinded or blinded only in name."

She noted that it's possible for patients to have a "spontaneous experience" without taking a hallucinogen.

"The Alcoholics Anonymous literature is full of people having that 'coming to God' moment that really triggers their recovery," she said.

"Promising" Findings

O'Donnell, who was one of the study therapists, said that for some cases, she couldn't tell whether a patient had received psilocybin or not.

Psilocybin may reduce alcohol dependence by restructuring the way patients view the world. "It might change what your orientation is to yourself and to others and to the drinking," said O'Donnell.

She described the new findings as "promising," but noted that alcoholism is "a highly chronic illness." However, even for those who relapse, this new approach may offer hope.

"If we can get people to engage in treatment, and if we can form a good rapport with them, then it's possible that even those who do relapse in future might come back into treatment and the trajectory would be different," said O'Donnell.

Psilocybin has been studied in the treatment for other addictions, including addiction to tobacco, as well as for other psychiatric conditions, such as depression and anxiety. O'Donnell's group is about to begin recruiting for a multisite trial of psilocybin in the treatment of major depressive disorder.

Other hallucinogens are being studied for various psychiatric conditions. A large phase 3 trial is investigating the use of MDMA, also known as ecstasy, for treating posttraumatic stress disorder.

Next Big Research Trend

Commenting on the research for Medscape Medical News, Sagar V. Parikh, MD, professor of psychiatry, University of Michigan, Ann Arbor, said that research into psilocybin and related drugs is "the next trend" in psychiatry.

"It's very early days, but I think there's enough science there to show something," he said.

Parikh noted that research on psychedelics dates back several decades. Indeed, a book published in the 1960s by a precursor of the Center for Addiction and Mental Health in Toronto, Canada, focused on the use of LSD in the treatment of alcoholism.

But overuse of psychedelics became a huge societal problem, which led to these drugs becoming controlled substances and a subsequent halt in related research, said Parikh.

Research is revving up again, he said.

He emphasized that the findings from this new study are very preliminary. "I'm hesitant to get too excited when it's the first study or two," he said.

He noted the current "tremendous treatment gaps" for alcohol use disorders. "None of the treatments we have are that effective, and they all rely on somewhat similar mechanisms," he said.

What's "exciting" about psilocybin is that there is some science to back it up, he said.

"From the basic science studies, psilocybin causes some long-term changes in small areas of the brain that are relevant to mood disorders and perhaps to addictions," he said.

Psychiatric research using psychedelic drugs "is still at beginning" stages, so it tends to concentrate on "the most prevalent disorders," such as alcohol dependence, depression, and anxiety, said Parikh.

"Since it's so hard to do research in this area, and expensive, people are concentrating on these big-ticket items," he said.

The study was funded by the Heffter Research Institute and by individual donations from Carey and Claudia Turnbull, Dr Efrem Nulman, and Rodrigo Nino.

American Psychiatric Association (APA) 2019: Abstract P6-17, session 6. Presented May 20, 2019.

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