Charles L. Raison, MD, returns to the Psychcast to conduct a Masterclass on psychedelics for patients with major depressive disorder.

Dr. Raison, professor of psychiatry at the University of Wisconsin–Madison, previously conducted a Masterclass on the risks and benefits of antidepressants. He disclosed that he is director of translational research at the Usona Institute, also in Madison.

Later, Renee Kohanski, MD, raises questions about the felony child abuse case of pediatric emergency department doctor John Cox.

Takeaway points

• Psychedelics are a range of compounds that share a common mechanism as agonists at the postsynaptic 5-HT2A serotonin receptor.
• Psychedelic agents have a novel therapeutic quality. Studies suggest that a few or even one exposure to a psychedelic compound, which has a short-term biological effect, leads to long-lasting therapeutic effect, such as remission of mood disorder or change in personality characteristics. The clinical outcomes are mediated by the intensity of the psychedelic experience.
• A psychedelic experience is characterized by profound, rapid alterations in what is seen, sensed, felt, and thought. It often leads to personal growth with experiences of transcendence. Subjects in trials often report a “mystical experience” they describe as a sense of unity with the universe and understanding of one’s deeper purpose. Psychedelic experiences also are characterized by a difficulty in describing them with words.
• Because psychedelics are illegal substances, the traditional route of pharmaceutical companies’ funding the research for clinical trials is not available. Organizations such as Usona Institute and MAPS (Multidisciplinary Association for Psychedelic Studies) are leading the way.
• The Food and Drug Administration has granted psilocybin a “breakthrough therapy designation” for the treatment of major depressive disorder.

Summary

• Psilocybin, lysergic acid diethylamide (LSD), mescaline, ayahuasca (active ingredient: N,N-dimethyltryptamine [DMT]), and 3,4-methylendioxy-methamphetamine (MDMA) are all classified as psychedelics. Psychedelics have been used for thousands of years for spiritual ceremonies.
• Psychedelics came to the attention of medicine and science after 1943 when Albert Hofmann, PhD, a chemist at a Sandoz Lab in Basel, Switzerland, synthesized LSD and accidentally ingested it, serendipitously identifying its mind-altering properties. 
• Until 1970, psychedelics were widely used in clinical research, and more than 1,000 academic papers about their use were published. For example, psychedelics were used as a model for schizophrenia and helped identify the role of serotonin in psychosis. They also were studied to treat addiction and as a treatment for existential anxiety in cancer. In 1971, psychedelics were declared illegal under the U.N. Convention on Psychotropic Substances.
• Researchers returned to psychedelics in the 2000s, examining a variety of uses, including the capability to reliably induce psychedelic experience in healthy normal volunteers (no previous psychiatric diagnosis) and promote emotional well-being in healthy normal volunteers. The role of psychedelics as medicine are once again being studied in a variety of contexts, such as mood disorders, PTSD, addiction, and phase-of-life problems.
• Most notable from the research is the capability of psychedelic compounds to induce long-lasting effects on personality, mood disorders, and PTSD after one or a few ingestions. What is remarkable is how the therapeutic effect remains long after the biological presence of the compound is gone from the body. The clinical outcomes are mediated by the intensity of the psychedelic experience.
• The Usona Institute, a medical research organization, started as a nonprofit to advance the research into psychedelics needed for the FDA to approve psychedelics as a treatment. Because psychedelics are still illegal, the traditional route of pharmaceutical companies funding this type of research is not available.
• The FDA has granted psilocybin a “breakthrough therapy designation” for the treatment of major depressive disorder. The breakthrough therapy designation “indicates that the drug may demonstrate substantial improvement on a clinically significant endpoint(s) over available therapies.”
• The breakthrough therapy designation is for major depressive disorder, not for treatment-resistant depression, suggesting that the FDA recognizes the shortcomings of current treatments for depression.

References

Johnson MW, Griffiths RR. Potential therapeutic effects of psilocybin. Neurotherapeutics. 2017 Jul;14(3):734-40.

Griffiths RR et al. Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning in trait measures of prosocial attitudes and behaviors. J Psychopharmacol. 2018 Jan;32(1):49-69.

Johnson MW et al.  Long-term follow-up of psilocybin-facilitated smoking cessation. Am J Drug Alcohol Abuse. 2017 Jan;43(1):55-60.

Griffiths RR et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-97.

Rozzo M. Book review: “‘How to Change Your Mind.” Columbia Magazine. 2018 Fall.

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