A novel psychedelic 5-HT 2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer
Gerard J. Marek, Soma Makai‐bölöni, Daniel Umbricht, Edward P. Christian, Jason Winters, Dino Dvořák, Shane Raines, Zoe Hughes, Eric W. Austin, Adam K. Klein, Wai Yie Leong, Fas J. Krol, Anne J. van der Graaf, Maria J Juachon, Marije E. Otto, Laura Borghans, Gabriël E. Jacobs, Andrew C Kruegel, Jonathan Sporn
Journal of Psychopharmacology October 16, 2025 DOI: 10.1177/02698811251378512 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Single-ascending dose, randomized, placebo-controlled, double-blind study Peer reviewed |
|---|---|
| Sample size | 48 |
| Population | Healthy participants |
| Intervention | GM-2505 |
| Dose | single IV doses up to 20 mg |
| Measures | resting-state electroencephalography (rsEEG) |
| Citations | 2 |
| Key points | GM-2505 demonstrated an acceptable safety profile and a shorter duration of cardiovascular and subjective effects than psilocybin but longer than DMT, with an optimal dose range of 10–15 mg IV for treating major depressive disorder. |
Abstract
Background: The treatment of major depressive disorder (MDD) with available antidepressant drugs is characterized by considerable ineffectiveness. Classical psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT), which act primarily as 5-hydroxytryptamine 2A (5-HT 2A ) receptor agonists, have shown preliminary efficacy for inducing long-term remission in MDD after one or two doses. GM-2505 is a novel, 5-HT 2A receptor agonist, developed for treating MDD.
Methods: In this single-ascending dose, randomized, placebo-controlled, double-blind study, we characterized GM-2505’s safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) profile in 48 healthy participants.
Results: Single intravenous (IV) doses up to 20 mg demonstrated an acceptable safety profile of mild transient adverse events, short-term, non-clinically significant increases in blood pressure and pulse, and no significant changes in electrocardiographs, consistent with other 5-HT 2A receptor agonists. In general, GM-2505 C max and AUC last increased dose proportionally, with t 1/2 of 40–50 minutes. Generally, dose-dependent effects were observed for neuroendocrine hormones, several neuropsychological and neurophysiological measures, and subjective drug effects. Dose-related effects were also observed in resting-state electroencephalography (rsEEG), with decreased power in the low frequency rsEEG bands (theta and alpha), and increased in the high frequency bands (slow and fast gamma).
Conclusions: These PD findings were similar in nature and magnitude to other 5-HT 2A receptor agonists that have been studied clinically. In line with the GM-2505 PK profile, the duration of cardiovascular and subjective effects was shorter than psilocybin but longer than DMT, demonstrating a potentially more practical temporal profile for use in a supervised clinical setting compared to longer-acting 5-HT 2A receptor agonists, with an optimal dose range of 10–15 mg IV. Clinical trial (ISRCTN64428072)
Registration: https://www.isrctn.com/ISRCTN64428072.