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Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression.
Peer-reviewte HumanstudieReviewPubMedFachartikel17. März 2022PMID: 34791625DOI
Abstract
Therapeutic deficiencies with monoaminergic antidepressants invites the need to identify and develop novel rapid-acting antidepressants. Hitherto, ketamine and esketamine are identified as safe, well-tolerated rapid-acting antidepressants in adults with treatment-resistant depression, and also mitigate measures of suicidality. Psilocybin is a naturally occurring psychoactive alkaloid and non-selective agonist at many serotonin receptors, especially at serotonin 5-HT2A receptors, and is found in the Psilocybe genus of mushrooms. Preliminary studies with psilocybin have shown therapeutic promise across diverse populations including major depressive disorder. The pharmacodynamic mechanisms mediating the antidepressant and psychedelic effects of psilocybin are currently unknown but are thought to involve the modulation of the serotonergic system, primarily through agonism at the 5-HT2A receptors and downstream changes in gene expression. It is also established that indirect effects on dopaminergic and glutamatergic systems are contributory, as well as effects at other lower affinity targets. Along with the direct effects on neurochemical systems, psilocybin alters neural circuitry and key brain regions previously implicated in depression, including the default mode network and amygdala. The aim of this review is to synthesize the current understanding of the receptor pharmacology and neuronal mechanisms underlying the psychedelic and putative antidepressant properties of psilocybin.
Autoren (15)
LeadMood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Department of Affective Disorders, The Affiliated Brain Hospital of Guangzhou Medical University, (Guangzhou Huiai Hospital), Guangzhou Medical University, Guangzhou, China.
Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada. roger.mcintyre@uhn.ca.