Psychedelics as anti-inflammatory agents
This review (2018) examines the cellular pathways through which psychedelics act as anti-inflammatory agents by means of selectively blocking the expression of pro-inflammatory mediators and thereby modulating histone modifications and epigenetic signaling. It is thus hypothesized that psychedelics may be of therapeutic value to a wide range of inflammatory disorders in humans.
Authors
- David Nichols
- Charles Nichols
Published
Abstract
Review: Serotonin (5-hydroxytryptamine, 5-HT)2A receptor agonists have recently emerged as promising new treatment options for a variety of disorders. The recent success of these agonists, also known as psychedelics, like psilocybin for the treatment of anxiety, depression, obsessive-compulsive disorder (OCD), and addiction, has ushered in a renaissance in the way these compounds are perceived in the medical community and populace at large. One emerging therapeutic area that holds significant promise is their use as anti-inflammatory agents. Activation of 5-HT2A receptors produces potent anti-inflammatory effects in animal models of human inflammatory disorders at sub-behavioural levels. This review discusses the role of the 5-HT2A receptor in the inflammatory response, as well as highlight studies using the 5-HT2A agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] to treat inflammation in cellular and animal models. It also examines potential mechanisms by which 5-HT2A agonists produce their therapeutic effects. Overall, psychedelics regulate inflammatory pathways via novel mechanisms, and may represent a new and exciting treatment strategy for several inflammatory disorders.
Research Summary of 'Psychedelics as anti-inflammatory agents'
Introduction
Psychedelics are a class of compounds that produce profound alterations in thought, mood and perception primarily through agonism of serotonin 5-HT2A receptors. Recent clinical work with classic psychedelics such as psilocybin has renewed interest in their therapeutic potential: placebo-controlled trials in patients with cancer-related psychosocial distress and open‑label work in depression have reported rapid and sometimes long-lasting improvements in mood, anxiety and life satisfaction. Concurrently, a growing literature links inflammation to the pathophysiology of psychiatric disorders, and the authors propose that anti‑inflammatory actions of 5-HT2A agonists may contribute to both rapid and durable clinical effects. This review, led by Flanagan and colleagues, sets out to examine the relationships among serotonin, inflammation and 5-HT2A receptor signalling, with particular emphasis on preclinical studies using 5-HT2A agonists (notably (R)-DOI). The paper aims to summarise cellular and animal evidence that 5-HT2A activation can produce potent anti‑inflammatory effects, outline possible mechanisms (including functional selectivity and epigenetic modulation), and consider therapeutic implications for inflammatory and neuropsychiatric disorders.
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Study Details
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Flanagan, T. W., & Nichols, C. D. (2018). Psychedelics as anti-inflammatory agents. International Review of Psychiatry, 30(4), 363-375. https://doi.org/10.1080/09540261.2018.1481827
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