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July 29, 2020

The Current Status of Psychedelics in Psychiatry

Author Affiliations
  • 1Imperial College London, London, United Kingdom
JAMA Psychiatry. Published online July 29, 2020. doi:10.1001/jamapsychiatry.2020.2171

In the 1950s, the Swiss pharmaceutical company Sandoz, which employed the chemist Albert Hofmann, who discovered lysergic acid diethylamide (LSD) and the similar serotonergic psychedelic psilocybin, made these drugs available to the psychiatric research community as the products Delysid and Indocybin, respectively. By the 1960s, these drugs had caused a revolution in brain science and psychiatry because of their widespread use by researchers and clinicians in many Western countries, especially the US. Before LSD was banned, the US National Institutes of Health funded more than 130 studies exploring its clinical utility, with positive results in a range of disorders but particularly anxiety, depression, and alcoholism. However, the displacement of LSD into recreational use and eventual association with the anti-Vietnam war movement led to all psychedelics being banned in the US. This ban became ratified globally under the 1971 UN Convention on narcotics. Since then, research funding, drug production, and the study of psychedelics as clinical agents has been virtually stopped. Until very recently, no companies would manufacture medical-grade psychedelics, which made getting regulatory approval for clinical research—especially clinical trials—very difficult and in some countries (eg, Germany) impossible.

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    1 Comment for this article
    Psilocybin in Psychiatry: An Additional Dose of History
    Brian Anderson, MD, MSc | UCSF / Zuckerberg San Francisco General Hospital
    We thank Drs. Nutt and Carhart-Harris for their Viewpoint on the Current Status of Psychedelics in Psychiatry. Their text provides a helpful overview of our field’s recent history, appropriately emphasizes that these are drug-assisted psychotherapies (vs purely pharmacotherapies), and correctly underscores the importance of clinical training for the future of these promising but complex interventions. We offer the following comments.

    Although infrequently-cited, Moreno et al.’s 2006 pilot study of psilocybin therapy for treatment-resistant obsessive-compulsive disorder (OCD)(1) was the first 21st-Century psilocybin trial conducted in a clinical population. Not only did this study jumpstart the current era of treatment studies
    with classic psychedelics, it also produced the first modern data in support of psilocybin’s ability to disrupt maladaptive, ruminative thoughts in a treatment-resistant psychiatric population. Shortly thereafter, Grob et al.’s pilot study of psilocybin therapy for anxiety in patients with advanced cancer,(2) which began in 2004, provided important safety and feasibility data that supported subsequent Phase 2 trials for anxiety and depression in cancer patients.(3) These pilot trials established with modern methodologies the proof-of-concept necessary for the use of moderate-to-high doses of oral psilocybin in psychiatric patients.

    It remains unclear what the optimum dose of psilocybin is for different patient populations. It is true that several recent trials in mood disorders have used a 25mg po fixed dose, but the majority of modern experience with psilocybin has been with weight-based dosing, with ‘high dose’ meaning 0.3-0.6mg/kg po, which often translates to doses much higher than 25mg. To date, no head-to-head comparisons have been made between psilocybin doses in the same patient population to assess comparative safety, efficacy, and durability of effect. And even though high-dose regimens have produced many of the impressive clinical outcomes cited in the literature,(3) they also likely carry greater safety risks than moderate doses, thus the need for careful attention to adequate screening and psychological support.

    There is as yet no standard dose of psychotherapy in psilocybin therapy trials. Some studies may limit preparation to a single visit the day before medication administration, but most recent trials have provided this behavioral support over several sessions spread out over days-to-weeks prior to the first medication session. To avoid some of the adverse reactions seen in the early days of psychedelic psychiatry,(4) we encourage investigators to offer robust preparation and trust-building prior to high-dose psilocybin treatments for clinical populations.

    Brian Anderson, MD, UCSF/ZSFG
    Alicia Danforth, PhD, Lundquist Institute
    Charles Grob, MD, Harbor-UCLA/Lundquist Institute

    1. Moreno FA, Wiegand CB, Taitano EK, Delgado PL. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry. 2006;67(11):1735-1740.
    2. Grob CS, Danforth AL, Chopra GS, et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry. 2011;68(1):71-78.
    3. Reiff CM, Richman EE, Nemeroff CB, et al. Psychedelics and psychedelic-assisted psychotherapy. Am J Psychiatry. 2020;177(5):391-410. doi:10.1176/appi.ajp.2019.19010035
    4. Johnson MW, Richards WA, Griffiths RR. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008;22(6):603-620. doi:10.1177/0269881108093587