Drug Companies Join Medical Psychedelic Movement—but Without the High


LSD and psilocybin in ‘magic mushrooms’ are among drugs getting redesigned

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.

Psilocybin, found in mind-bending mushrooms, is one of the compounds researchers hope can be developed into drugs that are safe enough to be taken at home.

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.

Psychedelics modified to remove their high might be less potent, some pharmacologists and researchers said, or might work for some conditions better than others. Some researchers said the trip might be essential to how psychedelics work in the brain.

Ketamine, seen being prepped by a nurse practitioner, and other mind-altering drugs are being developed for therapies with fewer heart-related side effects.

“We don’t know if the mechanism of healing from the classical psychedelics has anything to do with the experience,” said Dan Karlin, chief medical officer at Mind Medicine Inc., which is making a more chemically stable LSD that still imparts a high.

Evidence that hallucinogenic effects can be removed without diminishing a drug’s effectiveness comes mostly from animal studies. A study published in September in the journal Nature showed that drugs similar to LSD but without hallucinogenic effects made depression-prone mice more resilient to stressors such as being hung upside down.

The antidepressant effects of the experimental compounds were greater than those of some current antidepressants, said Brian Shoichet, a co-author of the study and professor of pharmaceutical chemistry at the University of California, San Francisco School of Pharmacy. In mice, the widely used proxy measure of hallucinations is head twitching, he said.

That doesn’t necessarily mean the compounds will have the same effects in people, researchers said“It’s a big jump from a mouse to a human,” said David Nutt, a neuropsychopharmacologist at Imperial College London and chief research officer at Awakn Life Sciences Corp., which is developing drugs including a shorter-acting MDMA-like compound.

Psychedelic drugs including psilocybin and LSD could help patients grow new neural connections in the brain, some studies in animals and people suggest. The trip, together with therapy, likely help people shift their mind-set and process past experiences, changing their outlook and patterns of thinking, Dr. Nutt and others said.

Other companies also are preserving the trip but patenting a change in the manufacturing process or formulation. Cybin Corp. is swapping out atoms in psilocybin to make it faster-acting, Chief Executive Officer Doug Drysdale said. Reunion Neuroscience Inc. said it expects early-stage clinical-trial safety data in early 2023 for a patented psilocybin-like drug tweaked to reduce how long the trip lasts.

Filament Health Corp. is making extracts of magic mushrooms and the psychedelic plant ayahuasca that contain a standard amount of active ingredient in each dose, said Ryan Moss, chief science officer.

“There’s a whole wealth of pharmaceutical knowledge that hasn’t been applied to this family of drugs yet,” said Henry Fisher, co-founder and chief scientific officer at Clerkenwell Health, a psychedelics research organization working on a clinical trial for a drug from Filament Health.