Molecular targets of psychedelic‐induced plasticity

Psychedelic research across different disciplines and biological levels is growing at a remarkably fast pace. In the prospect of a psychedelic drug becoming again an approved treatment, much of these efforts have been oriented toward exploring the relationship between the actual psychedelic effects...

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Bibliographic Details
Published in:Journal of neurochemistry 2022-07, Vol.162 (1), p.80-88
Main Authors: Jaster, Alaina M., Fuente Revenga, Mario, González‐Maeso, Javier
Format: Article
Language:English
Subjects:
5‐HT2A receptor
Antidepressants
GPCR
hallucinogens
LSD
Plasticity
Psychedelic drugs
psychedelics
Serotonin
Synaptic plasticity
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Summary:Psychedelic research across different disciplines and biological levels is growing at a remarkably fast pace. In the prospect of a psychedelic drug becoming again an approved treatment, much of these efforts have been oriented toward exploring the relationship between the actual psychedelic effects and those manifestations of therapeutic interest. Considering the central role of the serotonin 5‐HT2A receptor in the distinct effects of psychedelics in human psyche, neuropharmacology sits at the center of this debate and exploratory continuum. Here we discuss some of the most recent findings in human studies and contextualize them considering previous preclinical models studying phenomena related to synaptic plasticity. A special emphasis is placed on knowledge gaps, challenges, and limitations to evaluate the underpinnings of psychedelics’ potential antidepressant action. Tryptamine psilocin activates both serotonin 5‐HT1A and 5‐HT2A receptors, contributing to hallucinogenic‐like behavior, but the role of the 5‐HT1A in structural plasticity remains unknown. Phenethylamine DOI is more selective for 5‐HT2 receptors, with higher affinity to 5‐HT2AR, which contributes to both structural plasticity and hallucinogenic‐like behavior. Ergoline LSD activates dopamine D2 receptors as well as 5‐HT1A and 5‐HT2A receptors, which leads to hallucinogenic‐like behavior, but it is unknown how LSD’s polypharmacology influences synaptic structural plasticity.
ISSN:0022-3042
1471-4159
DOI:10.1111/jnc.15536