Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous RE104: A Double-Blind, Randomized, Single Ascending Dose Placebo-Controlled Study.
Guy Ludbrook, Nathan Bryson, Beatrix Taylor, Jasna Hocevar-Trnka, Matthew W Johnson, Joe Hirman, Glynn Morrish, Robert Alexander, Mark H Pollack
Journal of Clinical Psychopharmacology July 21, 2025 DOI: 10.1097/jcp.0000000000002047 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, placebo-controlled, phase 1 study Peer reviewed |
|---|---|
| Sample size | 48 |
| Population | Healthy adult participants with prior experiences with hallucinogenic or psychedelic compounds |
| Intervention | RE104 |
| Dose | 5 to 40 mg |
| Topics | Psilocybin |
| Keywords | 4‑substituted tryptamines Re104 Hallucinogens Pharmacokinetics This 4-substituted tryptamine 4-substituted tryptamines Predictable absorption Safety Well-tolerated Psychedelic effects effects Mystical experiences Shorter experience Shorter than psilocin Lasting 3-4 hours Favorable therapeutic profile Dose-finding dose-finding approach Correlated with dose |
| Citations | 2 |
| Key points | Single subcutaneous doses of RE104 up to 40 mg were safe and well-tolerated, produced dose-related psychedelic effects lasting 3 to 4 hours, and showed a favorable safety profile similar to psilocybin but with shorter duration. |
Abstract
This study is the first to formally evaluate in humans the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of RE104, a prodrug of the synthetic psychedelic known as 4-hydroxy-N,N-diisopropyltryptamine or 4-OH-DiPT. This double-blind, randomized, placebo-controlled, phase 1 study of single subcutaneous (SC) doses of RE104 (5 to 40 mg) included 6 cohorts and a total of 48 healthy adult participants with prior experiences with hallucinogenic or psychedelic compounds. SC doses of RE104 were generally safe up to 40 mg with no serious adverse events (AEs) or deaths. Most AEs occurred acutely under supervision and were mild to moderate. The Columbia-Suicide Severity Rating Scale score did not increase during the study, and the Assessment of Alertness and Sedation Scale was largely normal at all timepoints regardless of dose. RE104 exposure, based on Cmax, AUC0-t, and AUC0-inf, increased with dose from 5 to 40 mg RE104. 4-OH-DiPT appeared rapidly in plasma (median Tmax ranged from 1.0 to 1.25 hours across dose groups). Mean plasma 4-OH-DiPT t½ ranged from 2.72 hours to 4.12 hours. PKs appeared linear at the doses examined. Plasma levels of 4-OH-DiPT correlated with the Drug Effect Questionnaire and Mystical Experience Questionnaire (MEQ). Dose-related increases were observed in frequency of the MEQ 30 "complete mystical experience" responders. Single SC doses of RE104 resulted in a psychoactive experience and a favorable safety profile similar to psilocybin but with a shorter duration of psychoactive effect (3 to 4 hours). Results suggest a potential for therapeutic effect, warranting further study.