A new “magic mushroom” drug could treat depression without psychedelic hallucinations

Psilocin derivatives aim to treat depression by keeping serotonin pathway activity while reducing psychedelic-like effects. Researchers designed five modified forms of psilocin to release the active compound more slowly and steadily, then tested candidates in plasma and mouse models that simulate absorption and blood-brain exposure. The lead candidate, labeled 4e, showed stable absorption, gradual psilocin release, and serotonin receptor activation similar to pharmaceutical-grade psilocybin. In mice given oral doses, 4e reached the brain efficiently but produced fewer head twitches, an indicator used for psychedelic-like activity in rodents, compared with psilocybin. The work supports the idea that therapeutic serotonergic effects and hallucinogenic responses can be dissociated, pointing toward “safer and more practical” psychedelic-inspired medicines, pending additional biological and human safety research.