4e reduces psychedelic behavior in mice
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- Sara De Martin and co‑authors designed five fluorinated reversible N‑alkyl carbamate derivatives of psilocin to achieve sub‑hallucinogenic brain exposure.
- 4e showed strong stability in simulated gastrointestinal absorption and released psilocin gradually, yielding sustained brain levels with lower peak concentrations than pharmaceutical‑grade psilocybin.
- Mice given oral 4e displayed significantly fewer head‑twitches—a rodent indicator of psychedelic activity—compared with mice receiving psilocybin, despite comparable serotonin receptor activation.
- MGGM Therapeutics and NeuroArbor Therapeutics funded the research, and several authors hold patents on the new psilocin derivatives.
- Andrea Mattarei said the results support a growing view that psychedelic effects can be dissociated from therapeutic serotonergic activity, opening avenues for safer depression medicines.
Why it matters: Patients with depression gain a medication that taps serotonin‑targeting benefits of psilocybin without the disruptive hallucinations that limit its clinical use, while pharmaceutical developers acquire a new market for non‑hallucinogenic psychedelics and can leverage patented psilocin derivatives to expand their neuro‑psychiatric pipelines.
