A prodrug called RE104, which releases the short-acting psychedelic 4-OH-DiPT (structurally similar to psilocin), was characterized in rats. 4-OH-DiPT is a synthetic serotonin 2A receptor agonist with a reported 2-3 hour duration of psychedelic effects, shorter than psilocybin. RE104 incorporates a glutarate moiety that cleaves rapidly in the body to provide the active drug. In rats, plasma concentrations of 4-OH-DiPT correlated with head-twitch intensity, and its half-life was 40 minutes after subcutaneous RE104 administration. A single 1 mg/kg dose of RE104 significantly reduced immobility time in the forced swim test one week later, indicating potential antidepressant activity.
A single subcutaneous dose of RE104, a prodrug of the synthetic psychedelic 4-OH-DiPT, was generally safe and well-tolerated in 48 healthy adults with prior psychedelic experience. Doses from 5 to 40 mg produced no serious adverse events or deaths; most side effects were mild to moderate and occurred under supervision. The drug appeared rapidly in the blood, with peak levels reached in 1.0 to 1.25 hours and a half-life of 2.72 to 4.12 hours. Exposure increased proportionally with dose. Plasma levels correlated with drug effects and mystical experiences, and higher doses produced more complete mystical experiences. The psychoactive experience lasted 3 to 4 hours, shorter than psilocybin, suggesting a favorable therapeutic profile.