Feb 19, 2020
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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