d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology
International Journal of Molecular Sciences – November 23, 2016
Source: OpenAlex
Summary
Lysergic acid diethylamide (LSD) acts as a hallucinogen by profoundly influencing brain chemistry, offering a valuable pharmacological model for psychosis. Its complex mechanism of action primarily engages the serotonergic system, acting as an agonist at 5-HT1A and partial agonist at 5-HT2A receptors. Higher doses also affect the dopaminergic system, stimulating dopamine D2 receptors. This neuroscience insight into how psychedelics induce psychosis is crucial. Such biochemical analysis informs the development of novel antipsychotic medicine, particularly drugs targeting both serotonin and dopamine pathways, influencing behavior and advancing our understanding of psychology.
Abstract
d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles’ reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD’s mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D2, Trace Amine Associate receptor 1 (TAAR1) and 5-HT2A. More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD’s effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR1 receptors.