Psychedelic drugs are being reexamined as treatments for brain disorders, with hundreds of clinical trials underway by 2022. Emerging evidence suggests these drugs may produce lasting therapeutic effects by inducing structural and functional neural plasticity. The work reviews basic and clinical research on mechanisms, including receptor binding, gene expression, dendritic changes, and effects on microcircuitry and brain-wide circuits. It also outlines unmet clinical needs and unanswered neuroscience questions for future study.
A single dose of ketamine reactivates visual cortical plasticity in adult mice and restores visual acuity defects caused by amblyopia. Ketamine reduces neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons, leading to rapid and sustained decreases in synaptic inhibition to excitatory neurons and reduced synaptic excitation to PV neurons. These effects are blocked by adding NRG1 or removing its receptor from PV neurons. The findings indicate that ketamine's reactivation of adult visual cortical plasticity works through cortical disinhibition via downregulation of PV-specific NRG1 signaling, revealing a neural plasticity-based mechanism for functional recovery from adult amblyopia.