The serotonergic psychedelic DOI reduces anxiety-like behavior by activating 5-HT2A receptors on fast-spiking parvalbumin (PV)-positive interneurons in the CA1/subiculum region of the ventral hippocampus. Experiments combining anatomical, pharmacological, and genetic methods showed that these receptors are necessary for the anxiolytic effect. In vivo recordings revealed that DOI increases the firing rate of PV-positive interneurons, most of which express 5-HT2A receptors. Restoring 5-HT2A receptors specifically in PV-positive cells in a loss-of-function background reinstated DOI's anxiety-relieving effects, identifying these interneurons as a cellular trigger for psychedelic-induced relief of anxiety-like behavior.
Research on Schedule I substances in the United States is heavily restricted by the Controlled Substances Act, creating what is termed Research Harm—the restriction or deterrence of legitimate scientific inquiry due to governmental regulatory controls and criminal prohibitions. Barriers include lengthy DEA registration timelines, inconsistent guidance, and policy confusion, limiting access to substances with therapeutic potential like psilocybin, MDMA, cannabis, and DOI. The 2025 HALT Fentanyl Act introduces procedural improvements such as expedited registration and shared institutional access but leaves key regulatory issues unresolved. Recommended reforms include revising medical utility interpretations, conducting periodic evidence reviews, and establishing a scheduling framework for easier research access.