Safety, pharmacokinetics, and pharmacodynamics of intravenously administered deuterated N,N-dimethyltryptamine (CYB004) in healthy volunteers.
Katelijne V. van der Heijden, Gabriël E. Jacobs, Ellen James, Pradeep J Nathan, Marije E. Otto, Román Bohoslavsky, Marieke L De Kam, Joop van Gerven, Amir Inamdar
Journal of Psychopharmacology September 3, 2026 DOI: 10.1177/02698811261478616 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Population | Healthy volunteers |
| Intervention | CYB004 |
| Dose | 12.7 mg bolus and 15.41 mg infusion |
| Topics | DMT 5-MeO-DMT |
| Keywords | Deuteration Pharmacodynamics Pharmacokinetics Safety |
| Key findings | CYB004, a deuterated DMT analogue, produced psychedelic effects comparable to DMT at similar plasma concentrations but with a two-fold longer half-life, extending effects to ~40–60 minutes. Deuteration did not reduce pharmacokinetic variability, and safety was acceptable at clinically relevant exposures. |
Abstract
Serotonergic psychedelics, such as N,N-dimethyltryptamine (DMT), have shown therapeutic potential in various psychiatric disorders. However, DMT demonstrates pharmacokinetic (PK) variability and a short half-life. This exploratory study investigated the PK, pharmacodynamic (PD), and safety profile of CYB004, a deuterated DMT analogue, following intravenous administration in healthy volunteers. CYB004, a deuterated DMT analogue, was evaluated in a randomized, double-blind, placebo-controlled, two-part study in healthy participants. Part 1 was a single-dose cohort, in which participants received a 5-minute intravenous 12.7 mg CYB004 bolus, followed by a 30-minute 15.41 mg infusion. Part 2 was a three-way crossover, during which two separate 5-minute 12.7 mg CYB004 boluses were administered. Outcome measures included PK of CYB004 and subjective, autonomic, neurophysiological, and adverse effects. Although high CYB004 doses led to intense psychedelic experiences and participant withdrawals, lower doses achieving plasma concentrations similar to those in previous DMT studies demonstrated an acceptable safety profile. CYB004 demonstrated a PD profile that was similar to DMT at comparable plasma concentrations. PD effects consisted of subjective psychedelic effects, electroencephalography power band reductions, and autonomic nervous system activation. CYB004's half-life was approximately two-fold longer than DMT, prolonging the duration of psychedelic effects to ~40-60 minutes following brief intravenous administration. However, deuteration did not improve PK variability, with IV-administered CYB004 demonstrating moderate to high variability, largely driven by interindividual differences. CYB004 demonstrated PD effects comparable to DMT. However, CYB004 demonstrated an extended duration of these effects due to reduced clearance, while maintaining an acceptable safety profile at clinically relevant exposures despite PK variability.
Comparable studies
Other randomized controlled trials on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Psychological Effects of (S)-Ketamine and N,N-Dimethyltryptamine (DMT): A Double-Blind, Cross-Over Study in Healthy Volunteers Healthy volunteers | 2005 | Double-blind crossover study | n = 9 |
| Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans Experienced hallucinogen users | 1996 | Randomized controlled trial | n = 13 |
| Pharmacokinetics of N,N-dimethyltryptamine in Humans. Healthy adults | 2023 | Phase I component of a phase I/IIa randomised, double-blind, placebo-controlled, parallel-group, dose-escalation trial | n = 24 |
| Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis Healthy volunteers | 2007 | Double-blind crossover study | n = 15 |
Citations in the library
Cites 29
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Journal of Psychopharmacology October 6, 2015
and 24 more in the library