September 2023. A recent publication in Nature Neuroscience entitled “Psychedelics promote plasticity by directly binding to BDNF receptor TrkB”1 was headlined in a June 5 report in Science titled “Psychedelic-inspired drugs could relieve depression without causing hallucinations.”2 The study used a mouse animal model to differentiate the presumed antidepressant effects of psilocybin and LSD (by enhancing neuroplasticity) from the drugs’ hallucinogenic properties. Although it’s a long way from an animal model to studies in humans, this report is part of a groundswell of worldwide interest in psychedelic compounds as potential therapeutic agents for depression and other mental health conditions. Consider these examples in the academic world: the Center for Psychedelic & Consciousness Research at Johns Hopkins; the Berkeley Center for the Science of Psychedelics at the University of California; the Center for Psychedelic Medicine at NYU; the Center for Psychedelic Psychotherapy and Trauma Research at Mount Sinai; and the Transdisciplinary Center for Research in Psychoactive Substances at the University of Wisconsin—and this is far from a complete list.

I’m old enough to recall the turbulent period in the 1960s, when LSD was being studied in various academic centers as a potential therapeutic agent. However, this work was overshadowed by the risky “street drug” use of hallucinogens. In one look-back report entitled “LSD: a new treatment emerging from the past,” Erika Dyck3 described some of the controversies at the time, including concerns about flawed methodology in many research studies. She added: “By the mid-1960s, however, scientific criticism was somewhat moot. Research into LSD came to a decided halt, largely because it had become synonymous with countercultural activities, hedonism and drug abuse.”

So what accounts for this resurgence of interest in these notorious compounds for potential serious therapeutic use? Probably the primary driver for this trend has been the challenge to find effective interventions for “treatment-resistant depression”, reflecting the now well-known limits of our knowledge of how to help those with this seriously disabling condition. Take a look at the review article in this issue of the Journal by Amir Garakani and colleagues, entitled “Psychedelics, with a focus on psilocybin: Issues for the clinician.” In addition to his valuable role as JPP’s Clinical Case Editor, Garakani serves as a member of the Psychopharmacology Committee of the Group for the Advancement of Psychiatry (GAP). A recent focus of this group has been on the crescendo of interest in psychedelics, particularly psilocybin. This peer-reviewed report from the GAP Committee is chock-full of important information for practicing clinicians, examining potential benefits, risks, and ethical considerations as these compounds are re-examined, with scientific rigor. It’s important not to forget the pitfalls of the past, since unregulated use of these drugs is still a serious concern.

1. Moliner R, Girych M, Brunello CA, et al. Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nat Neurosci. 2023;26:1032–1041; Accessed July 14, 2023. https://www.nature.com/articles/s41593-023-01316-5 2. O’Grady C. Psychedelic-inspired drugs could relieve depression without causing hallucinations. Science. 2023. Accessed July 14, 2023. https://www.science.org/content/article/psychedelic-inspired-drugs-could-relieve-depression-without-causing-hallucinations. Also available at Science; 2023;5380(6649):999 under the title No trip needed for psychedelics to lift mood? 3. Dyck E. LSD: a new treatment emerging from the past. CMAJ. 2015;187:1079–1080.