A novel psychedelic 5-HT 2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer
Journal of Psychopharmacology – October 16, 2025
Source: OpenAlex
Summary
A new compound, GM-2505, a product of chemical synthesis and alkaloids, shows promise in psychedelics and drug studies for depression. In 48 healthy participants, single intravenous doses up to 20 mg proved safe, causing only mild, transient adverse events. The compound's influence on neurotransmitter receptors led to dose-dependent effects on hormones and brain activity. Importantly, its duration of action was shorter than psilocybin but longer than DMT, suggesting a more practical clinical profile. An optimal dose range appears to be 10-15 mg.
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.