This talk is part of the Michigan Psychedelic Center's 2026 Seminar Series: Psychedelics — From Cells to Society. Learn more about the series at https://michiganpsychedelic.med.umich.edu/education-events/.

About the Talk:
Newly Engineered Mouse Lines Reveal Rules for Psychedelic Neuroplasticity of Cortical Neurons Lacking 5-HT2a Receptors in Health and Alzheimer’s Disease

Classical psychedelic drugs show promise as a treatment for major depressive disorder and related neuropsychiatric disorders. This therapeutic efficacy is thought to involve neurons in the prefrontal cortex that express serotonin 2A receptors.

Here, using neural circuit cracking, genetic engineering, pharmacology, and machine learning, we discover extensive actions of psychedelic drugs that are independent of serotonin 2A receptors. We find that psychedelic drugs acutely target channels that are ubiquitously expressed across the brain and show that even neurons lacking serotonin 2A receptors can show a long-lasting boost in neuroplasticity after psychedelic treatment.

These results highlight a broader psychedelic therapeutic utility than currently appreciated and also suggest the need to be wary of actions on previously unexpected cells and synapses.