title: Psychedelics as Medicines: An Emerging New Paradigm.
abstract: Scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD; 5-HT2Areceptor 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.
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Nichols
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Johnson
authors.affiliation: Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Nichols
mesh_terms: D001007:Anxiety / Q000188:drug therapy; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002986:Clinical Trials as Topic; D003863:Depression / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D006213:Hallucinogens / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D008238:Lysergic Acid Diethylamide / Q000627:therapeutic use; D001523:Mental Disorders / Q000188:drug therapy*; D026441:Mind-Body Therapies / Q000379:methods; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy; D011562:Psilocybin / Q000627:therapeutic use; D011613:Psychotherapy / Q000379:methods; D044402:Receptor, Serotonin, 5-HT2A / Q000096:biosynthesis; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D012720:Severity of Illness Index; D019966:Substance-Related Disorders / Q000188:drug therapy
chemical_list: D006213:Hallucinogens; D018836:Inflammation Mediators; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D011562:Psilocybin; D008238:Lysergic Acid Diethylamide