Atai Therapeutics has received a USD 2.73 million UG3 cooperative agreement from the National Institute on Drug Abuse to advance non-hallucinogenic psychedelic-derived compounds for opioid use disorder (OUD), according to NIH Reporter. The award, granted under the UG3/UH3 mechanism that separates early optimization from later IND-enabling work, funds preclinical development of two lead chemical series rather than clinical testing.
The company's approach targets 5-HT2A/2C serotonin receptors, the same receptors activated by psilocybin, which has shown early signals of benefit in substance use disorders but carries hallucinogenic effects and 5-HT2B-related cardiac liabilities that complicate clinical use. Atai's lead compounds, designated EGX-J and EGX-I, reportedly show roughly 100-fold selectivity for 5-HT2A/2C over 5-HT2B in preliminary studies, an approach intended to retain psilocybin's polypharmacology while removing the need for supervised dosing sessions. Under the UG3 phase, Atai will optimize the compounds' drug-like properties and select a development candidate; a subsequent UH3 phase would fund manufacturing scale-up, IND-enabling toxicology and repeat-dose efficacy studies ahead of a first-in-human Phase I trial. No clinical data exist yet for either series.
The award reflects continued NIDA interest in medication development for OUD, an area where existing options—methadone, buprenorphine and naltrexone—carry adherence and misuse challenges. It also fits a broader pattern of "de-risked psychedelic" programs, alongside efforts by companies such as Delix Therapeutics and Gilgamesh Pharmaceuticals, seeking receptor-selective compounds without hallucinogenic effects. Principal investigator Glenn Short leads the project. Success in the UG3 phase, rather than the funding itself, will determine whether Atai's non-hallucinogenic strategy advances toward human testing.
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