Everything old is new again: are psychedelic medicines poised to take mental health by storm?

Three years ago, when I accepted a position as Director of Clinical and Translational Research at Usona Institute, a non-profit medical research organization pursuing a new drug indication for the psychedelic medicine psilocybin, many of my colleagues in mental health research looked at me like I had two heads. A year later, many of these same colleagues were beginning to ask me how they could become involved in ‘this exciting new field.’ Fast forward to the present and psychedelics are everywhere in the popular press, multiple entities are pursuing therapeutic indications for these agents and the world’s top psychiatric research institutions are beginning to talk about ‘centers for the study of psychedelic medicines.’ In three short years, I have had a front row seat to this amazing transformation, watching psychedelics go from the hippie fringe to the center of psychiatry, from being viewed with suspicion to potentially being over-sold. How is such a thing even possible? The first and deepest answer to this question derives, I believe, from the fact that we are desperate for new and better treatments in psychiatry and have been desperate for a long time. For example, although everyone who does clinical work has seen currently available antidepressants save lives, both literally and figuratively, they leave much to be desired in terms of both efficacy and tolerability; with a shadow side rarely discussed, which is that up to 25% of depressed patients who take these agents may have done better if they’d been given a placebo instead (1). Countering these dark musings is another, and brighter, reason for this explosion of interest in psychedelics. Over the last 3 years, studies have been published suggesting that these medicines have biological and behavioural effects that might make them uniquely valuable therapeutic agents for a range of mood and anxiety disorders. Like ketamine before them, psychedelic agents appear to do things that no one in mental health would have believed in advance, and would not believe now were it not for an increasingly consistent and hopeful database speaking to their efficacy. Psychedelics snuck into modern medicine in the mid-1990s with the pioneering work of Rick Strassman and colleagues, who reported on the biological and behavioural effects of the rapidly acting agent N,N-dimethyltryptamine (DMT) (2, 3) and with the multiple basic science studies conducted by Franz Vollenweider and colleagues at the University of Zurich (4). At the time for many of us this work seemed to come out of nowhere, a testimony to our profound amnesia regarding the central role that psychedelics had played in the development of biological psychiatry decades earlier, before they were made illegal and removed from research (5). Indeed, upwards of a thousand papers were published on classic psychedelics in the 1950s and 1960s. Although none of these studies come close to meeting modern norms for rigor, many of them suggested therapeutic benefits for two conditions in particular: alcoholism and end-of-life depression/anxiety in patients with terminal cancer. Based on these latter findings, as well as on a promising randomized trial in patients with cancer conducted by Charles Grob and colleagues at UCLA (6), when the door of possibilities opened a bit wider at the start of the 21st Century, researchers at Johns Hopkins and New York University (NYU) chose to use modern randomized, placebocontrolled, double-blind designs to examine whether the psychedelic agent psilocybin (the active ingredient in ‘magic mushrooms’) might really help depressed and anxious cancer patients. These studies were done on financial shoe-strings, funded mostly by the Heffter Research Institute. They were conducted against an impressive range of obstacles, and they took a long time to complete. When asked why psilocybin was the chosen agent, several of the researchers ruefully told me, ‘Because it didn’t contain the letters “L, S, D”.’ This honest confession spoke volumes about the