Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways
This book chapter (2018) describes the history, physiological response to psychedelics, and signaling pathway activated by serotonin (5-HT) 2A receptors.
Authors
- López-Giménez, J. F.
- González-Maeso, J.
Published
Abstract
The neuropsychological effects of naturally occurring psychoactive chemicals have been recognized for millennia. Hallucinogens, which include naturally occurring chemicals such as mescaline and psilocybin, as well as synthetic compounds, such as lysergic acid diethylamide (LSD), induce profound alterations of human consciousness, emotion, and cognition. The discovery of the hallucinogenic effects of LSD and the observations that LSD and the endogenous ligand serotonin share chemical and pharmacological profiles led to the suggestion that biogenic amines like serotonin were involved in the psychosis of mental disorders such as schizophrenia. Although they bind other G protein-coupled receptor (GPCR) subtypes, studies indicate that several effects of hallucinogens involve agonist activity at the serotonin 5-HT2A receptor. In this chapter, we review recent advances in understanding hallucinogen drug action through characterization of structure, neuroanatomical location, and function of the 5-HT2A receptor.
Research Summary of 'Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways'
Introduction
López-Giménez and colleagues frame the chapter within a long-standing interest in how hallucinogenic drugs — including mescaline, psilocybin and LSD — produce profound alterations in perception, emotion and cognition. Earlier pharmacological and clinical observations linked the actions of hallucinogens to the serotonergic system, and subsequent work identified the serotonin 5-HT2A receptor as a principal mediator of many hallucinogen effects. The Introduction therefore sets out the conceptual background of receptor pharmacology (especially G protein-coupled receptors, GPCRs) and the specific relevance of 5-HT2A receptors to the neuropsychological actions of hallucinogens. This chapter aims to review recent advances in understanding hallucinogen drug action by characterising the structure, neuroanatomical localisation and signalling functions of the 5-HT2A receptor. The authors focus on molecular and cellular signalling pathways, receptor–protein interactions and receptor complexes (notably with metabotropic glutamate receptors), and how these mechanisms may differentiate hallucinogenic from non‑hallucinogenic 5-HT2A agonists. The review emphasises translational links from cellular assays and rodent models to human neuropharmacology.
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Study Details
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- APA Citation
López-Giménez, J. F., & González-Maeso, J. (2017). Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways. Current Topics in Behavioral Neurosciences, 45-73. https://doi.org/10.1007/7854_2017_478
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