Psychedelics as Medicines: An Emerging New Paradigm

Serotonergic psychedelics like psilocybin and LSD, which activate 5-HT2A receptors, show preliminary efficacy in treating anxiety, depression, and addiction to tobacco and alcohol when combined with psychotherapy. Recent research suggests these compounds may also combat inflammatory diseases through novel mechanisms, potentially offering advantages over existing anti-inflammatory drugs. The authors propose that psychedelics work by temporarily destabilizing brain network hubs and global connectivity via amplified neuronal avalanches, allowing the brain to reset after acute effects subside. Anti-inflammatory effects could benefit both psychiatric and nonpsychiatric inflammation-related conditions, warranting rigorous further research.

Study at a glance

Abstract

Scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD; 5‐HT 2A receptor agonists) has dramatically increased within the last decade. Clinical studies administering psychedelics with psychotherapy have shown preliminary evidence of robust efficacy in treating anxiety and depression, as well as addiction to tobacco and alcohol. Moreover, recent research has suggested that these compounds have potential efficacy against inflammatory diseases through novel mechanisms, with potential advantages over existing antiinflammatory agents. We propose that psychedelics exert therapeutic effects for psychiatric disorders by acutely destabilizing local brain network hubs and global network connectivity via amplification of neuronal avalanches, providing the occasion for brain network “resetting” after the acute effects have resolved. Antiinflammatory effects may hold promise for efficacy in treatment of inflammation‐related nonpsychiatric as well as potentially for psychiatric disorders. Serotonergic psychedelics operate through unique mechanisms that show promising effects for a variety of intractable, debilitating, and lethal disorders, and should be rigorously researched.