The ABCs of psychedelics: a preclinical roadmap for drug discovery.
Trends Pharmacol Sci August 28, 2025 Alex C. Kwan, John R. Mantsch, John D. Mccorvy 7 citations
Developing psychedelic-inspired drugs for psychiatric disorders requires identifying analogs with ideal receptor selectivity and therapeutic efficacy. Recent advances include determining agonist-induced biased signal transduction, high-content behavioral phenotyping via automated video analysis, drug-evoked structural neural remodeling, and activity-dependent gene expression. This review outlines a framework for evaluating psychedelics and non-hallucinogenic serotonin 2A (5-HT2A) receptor agonists, critically examining methods for assessing agonism, behavior, and cellular plasticity. Emerging techniques that may improve translation to humans are highlighted. An effective discovery pipeline must align with specific experimental goals and incorporate multiple approaches for successful psychedelic drug development.