Do psychedelics have a role in psychiatric treatment?

UCLA Health psychiatrist Walter Dunn discusses the potential of psychedelic-assisted therapy at annual Integrative Medicine Symposium
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What if there was a medication that could significantly reduce symptoms of treatment-resistant depression after a single dose?

That drug may be psilocybin, the active ingredient in magic mushrooms, according to a recent study published in The New England Journal of Medicine.

UCLA Health psychiatrist Walter Dunn, MD, PhD shared this and other studies as he discussed the history, therapeutic potential and regulatory implications of psychedelic medicine during the 2023 Integrative Medicine Symposium presented by the David Geffen School of Medicine at UCLA.

In one study he cited, researchers found that a single dose of psilocybin lowered depression scores by an average of more than six points on the Montgomery-Asberg Depression Rating Scale (MADRS). Currently approved interventions for treatment-resistant depression generally reduce depression scores by two to four points on that scale, Dr. Dunn said.

In another study, published in The Lancet Psychiatry, people with treatment-resistant depression were given two doses of psilocybin four weeks apart. The results showed profound reductions in self-assessed depressive symptoms — about five times better than the results patients get from taking selective serotonin reuptake inhibitor (SSRI) antidepressants, which are currently the standard of care.

“These are unprecedented, unheard of” results, Dr. Dunn said. “We have nothing that works this well.” 

Also of note is the rapid action of these treatments, he added. Results were felt as early as the day after treatment and measurable for at least 12 weeks. “With SSRIs, we tell patients it will be six to eight weeks before they feel the maximum effect,” he said.

Gaining momentum

There is tremendous excitement about the therapeutic potential of psychedelics, Dr. Dunn said, both within the medical community and among the public.

Coverage in mainstream news media and books aimed at lay audiences (such as Michael Pollan’s “How to Change Your Mind,” which was also made into a Netflix series) have made magic mushrooms and MDMA topics of everyday conversation.

“When I go to dinner parties these days, when people find out my work is about psychedelics, my dance card is full,” Dr. Dunn said. “I’m talking about psychedelics for the rest of the evening.”

Federal funding agencies are also interested in psychedelics, he said. The National Institutes of Health, The National Academies of Sciences, Engineering and Medicine and the U.S. Department of Health and Human Services have all held recent workshops on the topic.

“We are in a historic moment in the space for psychedelic science, research and also mental health in general,” Dr. Dunn said. “There hasn’t been any time in modern psychiatry where there has been so much interest, awareness and discussion around a potential mental health treatment.”

While there are several studies and lots of conversation going on, these treatments are not widely available, as the U.S. Food and Drug Administration (FDA) and medical governing bodies have yet to approve psychedelics for therapeutic use or issue guidelines for best practices. 

The drugs come with risks, Dr. Dunn said.

“There are real harms and potential harms associated with these drugs and that's one of the reasons why the FDA has been very careful about how these trials are being run,” he said. “These are not benign medicines. Anything that can help you can harm you.”

What are psychedelics?

Some psychedelic substances, such as psilocybin, have been around for thousands of years. Others, such as MDMA and LSD, were synthesized in the 20th century.

These substances induce what researchers call “a non-ordinary state of consciousness,” Dr. Dunn said. “Some have described it as a mystical state, improving or inducing a sense of interconnectedness with the world around you.”

In therapeutic treatment, substances such as psilocybin or MDMA have been used to facilitate an “inner-directed” psychotherapy, he said. 

A patient undergoing psychedelic-assisted therapy would typically meet with a therapist for one or more appointments before receiving the psychedelic substance to discuss what to expect from the experience and to consider memories relevant to their psychological distress, Dr. Dunn said.

In research studies, the psychedelic medication is administered by two therapists in a non-clinical setting, he said: “It’s supposed to look like your living room. It’s supposed to be inviting, safe, and music is often played during the psychedelic dosing.” The patient is attended to throughout the six- to eight-hour experience.

Integration sessions with a therapist follow, during which the patient discusses what came up during the experience, what it means for them, and how to integrate lessons from the experience into their everyday life, Dr. Dunn said.

Regulatory considerations

The FDA is set to consider MDMA-assisted therapy for post-traumatic stress disorder (PTSD) in 2024, Dr. Dunn said, based on two phase three study results published in 2021, and then in September, 2023, in the journal Nature Medicine. In the 2023 study, 85% of participants with moderate to severe PTSD experienced “a clinically meaningful benefit,” and 71% of participants no longer met diagnostic criteria for PTSD by the end of the study.

Psychedelic-assisted therapy is “truly an integration between a regulated entity, the medicine, and unregulated entity, which is the psychotherapy,” Dr. Dunn said. “And I would argue — and I think most people would argue — that it would be difficult to pull those things apart and still claim the same safety and efficacy benefits.”

It’s unclear, he said, whether the FDA will require a Risk Evaluation and Mitigation Strategy (REMS), and what that would entail, if these treatments are approved. A REMS could require psychedelic-assisted therapy to include accompaniment by two specially trained and certified clinicians during the psychedelic experience. If so, that would reduce the pool of therapists who can administer the treatment and thus decrease access, even as it may enhance safety, Dr. Dunn said.

“Right now, enforcement and regulation is primarily in the hands of the DEA,” or Drug Enforcement Administration, Dr. Dunn said. “I have so many colleagues and patients ask me, ‘How do I get treatment with psychedelics? What clinics can I go to?’ So I need to remind them: This is still a Schedule 1 drug. There’s no clinical application for this quite yet. It’s still in the research realm.”

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