Microglia, the brain's resident immune cells, are emerging as a key target for new psychiatric drugs. This review examines how psychedelics (psilocybin, LSD), ketamine, and propofol interact with microglia to produce therapeutic effects. The authors detail pathways including sigma-1 receptors, serotonin and GABA signaling, and tryptophan metabolism through which these agents modulate microglial activity and inflammation, likely contributing to their benefits in mood disorders and addiction. The paper also discusses future directions, including implications for aging, glial cell heterogeneity, and advanced research methods.
Rapid-acting antidepressants, such as ketamine and serotonergic psychedelics, may affect myelin homeostasis. A systematic review of 41 studies (12 in humans, 21 in animals, 7 in vitro, and 1 computational) found that these drugs modulate myelination in a dose- and exposure-dependent manner: therapeutic doses generally promote myelin integrity and oligodendrocyte maturation, while high or repeated doses, or neonatal exposure, can disrupt myelin structure, impair oligodendrocyte viability, and produce cognitive, affective, and neurotoxic side effects. Myelin regulation may be a component of antidepressant action, but further research is needed to clarify mechanisms and implications for therapy.