Spotlight: Endocannabinoids, depression, and treatment resistance: Perspectives on effective therapeutic interventions (Rosa, et al, 2025)

"Ketamine and esketamine modulate CB1 receptors and other ECS targets, contributing to their rapid effects. Psilocybin restores 2-AG and enhances CB1 expression in mood-related brain regions, while LSD affects the broader endocannabinoidome in the prefrontal cortex and hippocampus."

Endocannabinoids, depression, and treatment resistance: Perspectives on effective therapeutic interventions - PubMed
Depression is a prevalent and heterogeneous disorder with significant personal and social consequences. The rise of treatment-resistant depression (TRD) challenges traditional approaches and underscores the need for a broader neurobiological perspective. When monoaminergic modulation proves insuffic …

These findings suggest that ECS modulation may constitute a unifying mechanism through which diverse, non-monoaminergic interventions exert antidepressant effects in TRD, positioning the ECS as a promising target of novel treatment strategies for individuals who do not respond to conventional treatments.
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