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

Psilocin derivatives aim to treat depression with fewer psychedelic-like effects by keeping serotonin-targeting activity while reducing hallucination risk. Researchers report that five engineered variants were designed to release psilocin more slowly and steadily after ingestion. In absorption simulation and human plasma tests, the candidate compound 4e showed strong stability and a gradual release profile while still activating key serotonin receptors. In mouse experiments comparing oral dosing of 4e versus pharmaceutical grade psilocybin, 4e reached the bloodstream and brain effectively and produced a lower but longer lasting brain exposure to psilocin. Behavioral measures also indicated reduced psychedelic-like activity, including fewer head twitches, suggesting that faster or higher peak release may contribute to hallucinogenic effects. The work is framed as a route to safer psychedelic-inspired therapeutics that retain potential antidepressant biology without intense mind-altering responses.