Brain activity of anandamide: a rewarding bliss?

Anandamide is a lipid mediator that acts as an endogenous ligand of CB1 receptors. These receptors are also the primary molecular target responsible for the pharmacological effects of Δ9-tetrahydrocannabinol, the psychoactive ingredient in Cannabis sativa . Several studies demonstrate that anandamid...

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Bibliographic Details
Published in:Acta pharmacologica Sinica 2019-03, Vol.40 (3), p.309-323
Main Authors: Scherma, Maria, Masia, Paolo, Satta, Valentina, Fratta, Walter, Fadda, Paola, Tanda, Gianluigi
Format: Article
Language:English
Subjects:
Amidohydrolases - antagonists & inhibitors
Anandamide
Animal models
Animals
Arachidonic Acids - physiology
Biomedical and Life Sciences
Biomedicine
Brain
Brain - drug effects
Brain - physiology
Cannabinoid CB1 receptors
Cannabis
Drug abuse
Drug-Seeking Behavior - drug effects
Endocannabinoids - physiology
Enzyme Inhibitors - pharmacology
Fatty-acid amide hydrolase
Humans
Hydrolase
Immunology
Inhibition
Internal Medicine
Medical Microbiology
Metabolic pathways
Metabolism
Pharmacology
Pharmacology/Toxicology
Polyunsaturated Alkamides
Reinforcement
Review
Review Article
Self Administration
Substance use
Tetrahydrocannabinol
Vaccine
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Description
Summary:Anandamide is a lipid mediator that acts as an endogenous ligand of CB1 receptors. These receptors are also the primary molecular target responsible for the pharmacological effects of Δ9-tetrahydrocannabinol, the psychoactive ingredient in Cannabis sativa . Several studies demonstrate that anandamide exerts an overall modulatory effect on the brain reward circuitry. Several reports suggest its involvement in the addiction-producing actions of other abused drugs, and it can also act as a behavioral reinforcer in animal models of drug abuse. Importantly, all these effects of anandamide appear to be potentiated by pharmacological inhibition of its metabolic degradation. Enhanced brain levels of anandamide after treatment with inhibitors of fatty acid amide hydrolase, the main enzyme responsible for its degradation, seem to affect the rewarding and reinforcing actions of many drugs of abuse. In this review, we will provide an overview from a preclinical perspective of the current state of knowledge regarding the behavioral pharmacology of anandamide, with a particular emphasis on its motivational/reinforcing properties. We will also discuss how modulation of anandamide levels through inhibition of enzymatic metabolic pathways could provide a basis for developing new pharmaco-therapeutic tools for the treatment of substance use disorders.
ISSN:1671-4083
1745-7254
DOI:10.1038/s41401-018-0075-x