Beyond the 5-HT2A Receptor: Classic and Nonclassic Targets in Psychedelic Drug Action.
Lindsay P. Cameron, Joseph Benetatos, Vern Lewis, Emma M. Bonniwell, Alaina M Jaster, Rafael Moliner, Eero Castrén, John D. Mccorvy, Mikael Palner, Argel Aguilar-Valles
Journal of Neuroscience November 8, 2023 DOI: 10.1523/jneurosci.1384-23.2023 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | Psychedelics Brain chemistry Mental health Pharmacology |
| Citations | 88 |
| Key findings | Serotonergic psychedelics promote neuroplasticity through 5-HT2A receptor activation and other interactions, which may underlie their therapeutic potential for mental health conditions. |
Abstract
Serotonergic psychedelics, such as psilocybin and LSD, have garnered significant attention in recent years for their potential therapeutic effects and unique mechanisms of action. These compounds exert their primary effects through activating serotonin 5-HT2A receptors, found predominantly in cortical regions. By interacting with these receptors, serotonergic psychedelics induce alterations in perception, cognition, and emotions, leading to the characteristic psychedelic experience. One of the most crucial aspects of serotonergic psychedelics is their ability to promote neuroplasticity, the formation of new neural connections, and rewire neuronal networks. This neuroplasticity is believed to underlie their therapeutic potential for various mental health conditions, including depression, anxiety, and substance use disorders. In this mini-review, we will discuss how the 5-HT2A receptor activation is just one facet of the complex mechanisms of action of serotonergic psychedelics. They also interact with other serotonin receptor subtypes, such as 5-HT1A and 5-HT2C receptors, and with neurotrophin receptors (e.g., tropomyosin receptor kinase B). These interactions contribute to the complexity of their effects on perception, mood, and cognition. Moreover, as psychedelic research advances, there is an increasing interest in developing nonhallucinogenic derivatives of these drugs to create safer and more targeted medications for psychiatric disorders by removing the hallucinogenic properties while retaining the potential therapeutic benefits. These nonhallucinogenic derivatives would offer patients therapeutic advantages without the intense psychedelic experience, potentially reducing the risks of adverse reactions. Finally, we discuss the potential of psychedelics as substrates for post-translational modification of proteins as part of their mechanism of action.
Comparable studies
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- Impact of psilocybin on cognitive function: A systematic review Psychiatry and Clinical Neurosciences October 1, 2024
- 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents - A Review. ACS Pharmacology & Translational Science June 14, 2024
- Therapeutic Potential of Psychedelic Drugs: Navigating High Hopes, Strong Claims, Weak Evidence, and Big Money Annual Review of Psychology August 2, 2024
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Cites 58
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
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