Psychedelics Promote Structural and Functional Neural Plasticity
By Calvin Ly, Alexandra C. Greb, Lindsay P. Cameron, Kassandra M. Ori-McKenney, John A. Gray, D. E. Olson, J. Wong, Eden V. Barragan, P. Wilson, Kyle F Burbach and 6 more. Cell Reports, 2018
1,026 citations recorded by the source corpus.
SUMMARY Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders.
Subfields: Cellular and Molecular Neuroscience, Clinical Psychology, Organic Chemistry
View Paper: https://www.semanticscholar.org/paper/ff8f30c045c392110cb0b8229c2aae1f515d2084
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Citations in the corpus
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics (2019, background): “Taken together, the above-cited findings speak to the notion that the brain enters an entropic hot state under psychedelics in which synaptic efficacy and plasticity are elevated (Ly et al., 2018).”
- Psilocybin-assisted therapy of major depressive disorder using Acceptance and Commitment Therapy as a therapeutic frame (2020, methodology): “Additionally, the research study of which the ACT protocol described here is a part(3) is further investigating the hypothesis that psilocybin induces a transient neuroplastic brain state (Ly et al., 2018).”