Drug Companies Join Medical Psychedelic Movement—but Without the High

Drug developers are designing new psychedelic compounds to treat depression and other mental-health conditions but skip the trip.

Mind-bending psychedelics including MDMA (aka “ecstasy”), “magic mushrooms” and LSD are being studied as potential treatments for depression, post-traumatic stress disorder and addiction. Dozens of companies and academic laboratories are also making changes to the structure of those drugs, or designing similar compounds, to take advantage of their therapeutic properties without the high.

Human research on the newly developed compounds is just getting started. Some researchers and analysts said the trip itself could be critical to the therapeutic benefit for patients.

Drugs including psilocybin and mescaline aren’t patentable because they occur naturally in mushrooms or plants. Others including LSD and MDMA were created in labs decades ago. Global revenue from psychedelics could reach $8 billion by 2027, L.E.K. Consulting estimated.

Psychedelic drugs are tightly regulated. Some including MDMA impart effects that last for hours and require patient supervision during medical use. Companies and researchers said creating new compounds with shorter-acting or non-hallucinogenic effects could lead to fewer restrictions, and make them easier for doctors and patients to use.

New drugs could also open their use to people who are currently excluded from psychedelic treatment for safety reasons, including a history of schizophrenia or some heart conditions, they said.

“We have to create medicines that are safe enough that people can take them at home and put them in their medicine cabinet,” said David Olson, chief innovation officer at Delix Therapeutics, which is developing drugs similar to substances such as LSD and psilocybin but without the trip. The company said it raised some $100 million and plans to move two drugs into human trials next year.

Psilera Inc. says it is working on derivatives of psilocybin and the psychedelic DMT, but without the trip and with fewer heart-related side effects. HMNC Brain Health said it is conducting clinical trials on a version of ketamine to treat depression that could reduce its mind-altering effects and hasn’t shown signs of raising blood pressure. Small Pharma said it is developing longer-acting versions of DMT, which typically produces an intense minutes-long trip.

“If you can dial down the risk or perhaps turn the dial up in terms of the effectiveness, that’s the sort of thing that we’re looking for,” said Clara Burtenshaw, a partner at Neo Kuma Ventures, a venture-capital fund invested in psychedelic companies including Small Pharma.

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