Cell Reports
Volume 23, Issue 11, 12 June 2018, Pages 3170-3182
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Article
Psychedelics Promote Structural and Functional Neural Plasticity

https://doi.org/10.1016/j.celrep.2018.05.022Get rights and content
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Highlights

  • Serotonergic psychedelics increase neuritogenesis, spinogenesis, and synaptogenesis

  • Psychedelics promote plasticity via an evolutionarily conserved mechanism

  • TrkB, mTOR, and 5-HT2A signaling underlie psychedelic-induced plasticity

  • Noribogaine, but not ibogaine, is capable of promoting structural neural plasticity

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.

Keywords

neural plasticity
psychedelic
spinogenesis
synaptogenesis
depression
LSD
DMT
ketamine
noribogaine
MDMA

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