In the 1950s and early 1960s, researchers within both academic and governmental institutions extensively investigated the clinical potential of psychedelic drugs, notably both LSD and psilocybin, the psychoactive substance in “magic mushrooms.” This early research aimed to understand the biological underpinnings of schizophrenia and to find new treatments for psychological disorders such as depression, anxiety and addictive behaviors.
With the popularization of LSD by authors such as Aldous Huxley and, later, Harvard psychologist Timothy Leary, both therapeutic and recreational use of psychedelic drugs began to spread. In response to the drugs gaining such popularity, and as a reaction to the severe birth defects resulting from thalidomide use, regulators sought to greatly tighten governmental oversight of all investigational drugs. The U.S. Congress passed the Kefauver-Harris Drug Amendments in 1962, requiring the U.S. Food and Drug Administration to approve all testing of investigational drugs. But while this constrained clinical investigations with LSD, it did not thwart the popularity of the drug’s illegitimate use, which further increased throughout the 1960s. In response, laws overseeing the general availability and use of psychedelic drugs were tightened even more, ultimately culminating in the passage of the Controlled Substances Act in 1970. The new statute classified psychedelics — along with marijuana, MDMA (ecstasy), and heroin — as Schedule I Substances with “no currently accepted medical value and a high potential for abuse,” which halted nearly all research on these compounds in the United States. U.S. governmental pressure also induced many other nations to institute similar controls on human studies with psychedelic drugs, although some private research continued in Europe on the use of LSD, ketamine and MDMA in psychotherapy.
Research on psychedelic drugs in the United States began to slowly re-emerge in the early 2000s when Johns Hopkins Medicine obtained FDA approval to administer such drugs to healthy human subjects. A handful of other private institutions have followed with studies of psilocybin to treat depression, end-of-life anxiety, addiction and other conditions, and of MDMA to treat post-traumatic stress disorders (PTSD).
Psychedelics have to date remained tightly controlled Schedule I drugs, thus banning the National Institutes of Health (NIH) from funding human studies. But interest in the therapeutic potential of psychedelic drugs has continued to grow and new funding for clinical research is emerging from the private sector, including non-profit foundations such as the Multidisciplinary Association for Psychedelic Studies and a few Silicon Valley, European and Canadian investors (many of whom had successfully invested in cannabis companies and are now looking for new opportunities).
In September, backed by $17 million in private funding, Johns Hopkins Medicine opened the Center for Psychedelic and Consciousness Research. The Center plans to explore the use of psychedelic drugs to treat psychiatric disorders, as well as to investigate their impact on creativity and well-being. The first clinical trials will focus on explorations of psilocybin as a treatment for opioid addiction, cognitive deficits in early Alzheimer’s disease, PTSD, and mood and alcohol-related problems. A smaller center for psychedelic research also opened in April at Imperial College in London with $3.5 million in funding from private sources.
So far, most established pharmaceutical and biotechnology companies — and most conventional pharmaceutical investors — have kept away from psychedelic drug development, put off by the illegality of the drugs in many countries and by their “party-drug” reputation. A notable exception, Johnson & Johnson, received FDA approval this year for Spravato (esketamine), a stereo-isomer version of ketamine — an approved anesthetic that also has a history of abuse — for the in-clinic treatment of severe depression. The reluctance of pharmaceutical companies to explore the therapeutic benefits of psychedelics is likely to evolve over time, similarly to what has happened with cannabis-based products, where approval of GW Pharma’s Epidiolex (cannabidiol) has opened the way to an increasing number of firms studying such drugs.
At the same time, a few start-up companies have been founded to explore the development of psychedelic medicines. German company ATAI Life Sciences AG is applying a big data approach to neuropsychiatric drug development, partnering and investing in other start-ups with a focus on specific types of drugs, including psychedelics. Compass Pathways, Inc., a UK-based company that is one of ATAI’s investments, has received FDA approval to conduct U.S. clinical trials of psilocybin in patients with treatment-resistant depression. Together, ATAI and Compass have raised $122 million from investors to support their efforts.
Recently founded Mind Medicines, Inc. (MindMed) is taking a somewhat different approach with their first development program, which is focused on a psychedelic-inspired drug called 18-MC. The chemical structure of 18-MC is based on the powerful plant-derived psychedelic ibogaine, which has been used in some places outside the United States to treat opioid addiction, but 18-MC lacks ibogaine’s hallucinogenic and cardiotoxic properties. Initially developed by Stanley Glick at Albany Medical College and U.S. company Savant HWP, with early grant funding from the NIH’s National Institute on Drug Abuse, 18-MC has shown strong anti-addictive effects in multiple animal models. The drug has completed an initial human safety study conducted by Savant’s development partner in Brazil, confirming 18-MC’s lack of hallucinogenic properties. MindMed is now making plans to conduct trials in the United States, with an initial focus on opioid addiction.