Psychedelics excite hippocampal cells to reduce anxiety: DOI activates inhibitory interneurons in ventral hippocampus in mice and rats

Psychedelic DOI (2,5-dimethoxy-4-iodoamphetamine) reduces anxiety-like behavior in mice and rats while activating ventral hippocampus fast-spiking interneurons. The study links DOI's anxiolytic effects to parvalbumin interneurons that silence neighboring neurons in the ventral hippocampus, a brain region tied to emotion and social memory. Importantly, this circuitry is presented as distinct from pathways that produce the hallmark hallucinations of classic psychedelics. The findings suggest anxiety relief and hallucination-like effects may be separable, motivating development of psychedelic-inspired drugs that target anxiety without potent perceptual side effects.