Format

Send to

Choose Destination
Int J Mol Sci. 2016 Nov 23;17(11). pii: E1953.

d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology.

Author information

1
Neurobiological Psychiatry Unit, McGill University, Montreal, QC H3A 1A1, Canada. danilo.degregorio@mail.mcgill.ca.
2
Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, 20132 Milan, Italy. comai.stefano@hsr.it.
3
Neurobiological Psychiatry Unit, McGill University, Montreal, QC H3A 1A1, Canada. luca.posa@mail.mcgill.ca.
4
Neurobiological Psychiatry Unit, McGill University, Montreal, QC H3A 1A1, Canada. gabriella.gobbi@mcgill.ca.

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.

KEYWORDS:

LSD; TAAR1; atypical antipsychotics; dopamine; hallucinogens; psychosis; serotonin

PMID:
27886063
PMCID:
PMC5133947
DOI:
10.3390/ijms17111953
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare that they have no competing interest.

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center