Bretisilocin
Bretisilocin, also known by its developmental code name GM-2505 and as 5-fluoro-N-methyl-N-ethyltryptamine, is a serotonergic psychedelic of the tryptamine family which is under development for the treatment of major depressive disorder. It is an analogue of dimethyltryptamine and is the 5-fluorinated derivative of methylethyltryptamine. Bretisilocin's route of administration is intravenous infusion.
The drug acts as a potent and well-balanced serotonin 5-HT2A and 5-HT2C receptor agonist, serotonin 5-HT2B receptor partial agonist or antagonist, and serotonin releasing agent. It produces psychedelic-like effects in animals and similarly produces robust hallucinogenic effects in humans. The duration of bretisilocin is 60 to 90minutes and is intermediate between the durations of DMT and psilocybin. It has been regarded by its developer as an improvement of DMT.
Bretisilocin was first described in the literature by 2022. It is under development by Gilgamesh Pharmaceuticals. As of June 2025, the drug is in phase 2 clinical trials for the treatment of major depressive disorder. Bretisilocin was acquired from Gilgamesh Pharmaceuticals by AbbVie in a deal worth up to $1.2billion in August 2025.
Use and effects
Bretisilocin, given by intravenous injection, produces threshold psychedelic effects at doses of 1mg and 3.3mg, has an optimal dose range of 10 to 15mg, and produces particularly intense effects at a dose of 20mg. The drug's effects at doses of 15 to 20mg were described as equivalent to or greater than those of 30mg psilocybin or 100 to 200μg LSD based on rating scales. The 20mg dose of bretisilocin was associated with more challenging experiences including anxiety, cognitive impairment, and dread of ego dissolution, which led to selection of a lower optimal dose range of 10 to 15mg. Compared to other psychedelics like psilocybin and LSD, bretisilocin has a much shorter duration, but is longer-lasting than DMT. Its duration is about 60 to 90minutes, whereas psilocybin has a duration of multiple hours and DMT has a duration of as short as 10minutes. The psychedelic effects of bretisilocin are generally resolved by approximately 2hours after administration, but have been found to last up to 4 to 6hours in some individuals. Peak effects occur about 10 to 20minutes following injection.File:Pharmacokinetics and effects of bretisilocin at different doses by intravenous injection in humans.png|thumb|left|250px|class=skin-invert-image|Circulating levels and psychedelic subjective effects of bretisilocin at doses of 0.34 to 20mg by intravenous injection.
The drug, administered intravenously in clinical studies, produces effects in humans including "altered states of consciousness, altered visual depth perception, abnormal thinking, euphoric mood, feeling drunk, feeling of body temperature changes, relaxation, sensory processing disorder, sensory overload, and time perception altered". The subjective effects of bretisilocin were described as very robust and consistent in strength with the effects of other psychedelics including LSD, DMT, and psilocybin as have been reported in clinical studies.
Side effects
s of bretisilocin include acute sensory processing disorder, altered state of consciousness, abnormal thinking, euphoric mood, fatigue, and small increases in heart rate and blood pressure, among others. Adverse effects like fatigue and headache occur after the psychedelic experience and can persist for up to 24hours after administration.Interactions
Pharmacology
Pharmacodynamics
Bretisilocin acts as a potent and well-balanced serotonin 5-HT2A and 5-HT2C receptor agonist, serotonin 5-HT2B receptor antagonist, and serotonin releasing agent. In another study however, it was a moderate-efficacy partial agonist of the serotonin 5-HT2B receptor. The drug appears to have negligible activity as a serotonin 5-HT1A receptor agonist. However, another study found that it was a serotonin 5-HT1A receptor full agonist, with an at this receptor that was about 44-fold less potent than at the serotonin 5-HT2A receptor.The affinity of bretisilocin for the serotonin 5-HT2A receptor was 4.9nM with DOI as the radioligand and 140–191nM with ketanserin as the radioligand. Its values were 15.0–20.6nM at the serotonin 5-HT2A receptor and 9.5nM at the serotonin 5-HT2C receptor, whereas its at the serotonin 5-HT2B receptor was 5.8nM. It showed much higher efficacy at the serotonin 5-HT2A receptor than its parent compound MET. Bretisilocin showed very weak activity at the serotonin 5-HT1A receptor. In addition to its actions at the serotonin 5-HT2 receptors, it is a partial serotonin releasing agent in rat brain synaptosomes, with an of 8.4–15.7nM and an of 66.8–71.4%. Bretisilocin is also a serotonin reuptake inhibitor to a much weaker extent. Additional values have also been published.
Bretisilocin is related to DMT and is considered by its developer to be an improved version of DMT. It also induces more serotonin release than DMT, which may provide it with more entactogen-like qualities compared to DMT. Bretisilocin produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. It shows antidepressant-like effects in rodents. The drug dose-dependently produces hypolocomotion in rodents similarly to many other serotonergic psychedelics. Likewise, it produces anti-obsessional effects in the form of reduced marble burying in rodents. Bretisilocin does not produce conditioned place preference in rodents, suggesting lack of reinforcing properties.