title: d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology.
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-HT2Areceptor as a partial agonist and 5-HT1Aas 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.
authors.affiliation: Neurobiological Psychiatry Unit, McGill University, Montreal, QC H3A 1A1, Canada. danilo.degregorio@mail.mcgill.ca.
authors.forename: Danilo
authors.initials: D
authors.lastname: De Gregorio
authors.affiliation: Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, 20132 Milan, Italy. comai.stefano@hsr.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Comai
authors.affiliation: Neurobiological Psychiatry Unit, McGill University, Montreal, QC H3A 1A1, Canada. luca.posa@mail.mcgill.ca.
authors.forename: Luca
authors.initials: L
authors.lastname: Posa
authors.affiliation: Neurobiological Psychiatry Unit, McGill University, Montreal, QC H3A 1A1, Canada. gabriella.gobbi@mcgill.ca.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gobbi
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004353:Drug Evaluation, Preclinical; D006213:Hallucinogens / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008238:Lysergic Acid Diethylamide / Q000378:metabolism / Q000494:pharmacology*; D011618:Psychotic Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000095383:Trace Amine-Associated Receptors
chemical_list: D014150:Antipsychotic Agents; D004298:Dopamine; D006213:Hallucinogens; D008238:Lysergic Acid Diethylamide; D044282:Receptor, Serotonin, 5-HT1A; D044402:Receptor, Serotonin, 5-HT2A; D011954:Receptors, Dopamine; D043562:Receptors, G-Protein-Coupled; D017470:Receptors, Glutamate; D017366:Serotonin Receptor Agonists; D000095383:Trace Amine-Associated Receptors
keywords: LSD; TAAR1; atypical antipsychotics; dopamine; hallucinogens; psychosis; serotonin