Catalysts for change: the cellular neurobiology of psychedelics
This Perspective argues that classical psychedelics act as catalysts of neural plasticity by engaging diverse cellular and subcellular signalling pathways — interacting with stress and inflammation — which likely underpin their therapeutic effects. The authors contend that this mechanistic complexity both mirrors the heterogeneity of psychiatric disorders and reshapes our understanding of mood, behaviour and consciousness.
Authors
- Bement, W.
- Banks, M. I.
- Zahid, Z.
Published
Abstract
The resurgence of interest in the therapeutic potential of psychedelics for treating psychiatric disorders has rekindled efforts to elucidate their mechanism of action. In this Perspective, we focus on the ability of psychedelics to promote neural plasticity, postulated to be central to their therapeutic activity. We begin with a brief overview of the history and behavioral effects of the classical psychedelics. We then summarize our current understanding of the cellular and subcellular mechanisms underlying these drugs’ behavioral effects, their effects on neural plasticity, and the roles of stress and inflammation in the acute and long-term effects of psychedelics. The signaling pathways activated by psychedelics couple to numerous potential mechanisms for producing long-term structural changes in the brain, a complexity that has barely begun to be disentangled. This complexity is mirrored by that of the neural mechanisms underlying psychiatric disorders and the transformations of consciousness, mood, and behavior that psychedelics promote in health and disease. Thus, beyond changes in the brain, psychedelics catalyze changes in our understanding of the neural basis of psychiatric disorders, as well as consciousness and human behavior.
Research Summary of 'Catalysts for change: the cellular neurobiology of psychedelics'
Introduction
Human use of psychedelic compounds spans millennia, from traditional ceremonial and medicinal contexts to modern clinical research. Bement and colleagues note that naturally occurring agents such as ayahuasca (containing DMT), 5-MeO-DMT, and psilocybin have long cultural histories, whereas synthetic compounds such as LSD were introduced in the 20th century. After decades of restricted research following regulatory scheduling, human research has resumed and small clinical trials over the past 20 years have reported promising, sometimes durable, therapeutic effects for conditions including depression, anxiety, substance use disorders, and obsessive–compulsive disorder. The authors emphasise that the intensity of the acute subjective psychedelic experience often correlates with subsequent therapeutic benefit, and that single or a few doses of psilocybin can produce symptomatic relief lasting months in some participants. This Perspective sets out to examine the cellular and subcellular mechanisms that could link the acute pharmacology and phenomenology of psychedelics to the longer-term structural and behavioural changes seen in humans. The investigators focus particularly on neural plasticity as a putative central mechanism, and outline current understanding of receptor signalling, interactions with glutamatergic systems, electrophysiological and network effects, gene expression and structural plasticity, and the roles of stress and inflammation in acute and lasting drug actions. The aim is to synthesise mechanistic insights that might explain how transient drug exposures produce protracted changes in mood and behaviour and to identify key unanswered questions for future research.
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- APA Citation
Banks, M. I., Zahid, Z., Jones, N. T., Sultan, Z. W., & Wenthur, C. J. (2021). Catalysts for change: the cellular neurobiology of psychedelics. Molecular Biology of the Cell, 32(12), 1135-1144. https://doi.org/10.1091/mbc.e20-05-0340
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