Modulation of Endocannabinoid System Components in Depression: Pre-Clinical and Clinical Evidence

Uri Bright, Irit Akirav

Research output: Contribution to journalReview articlepeer-review

Abstract

Depression is characterized by continuous low mood and loss of interest or pleasure in enjoyable activities. First-line medications for mood disorders mostly target the monoaminergic system; however, many patients do not find relief with these medications, and those who do suffer from negative side effects and a discouragingly low rate of remission. Studies suggest that the endocannabinoid system (ECS) may be involved in the etiology of depression and that targeting the ECS has the potential to alleviate depression. ECS components (such as receptors, endocannabinoid ligands, and degrading enzymes) are key neuromodulators in motivation and cognition as well as in the regulation of stress and emotions. Studies in depressed patients and in animal models for depression have reported deficits in ECS components, which is motivating researchers to identify potential diagnostic and therapeutic biomarkers within the ECS. By understanding the effects of cannabinoids on ECS components in depression, we enhance our understanding of which brain targets they hit, what biological processes they alter, and eventually how to use this information to design better therapeutic options. In this article, we discuss the literature on the effects of cannabinoids on ECS components of specific depression-like behaviors and phenotypes in rodents and then describe the findings in depressed patients. A better understanding of the effects of cannabinoids on ECS components in depression may direct future research efforts to enhance diagnosis and treatment.

Original languageEnglish
Article number5526
JournalInternational Journal of Molecular Sciences
Volume23
Issue number10
DOIs
StatePublished - 1 May 2022

Bibliographical note

Funding Information:
This research was supported by a grant from the Israel Science Foundation (ISF) (https://www.isf.org.il/#/, accessed on 29 March 2022) (992/20) to I.A.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • cannabinoids
  • cannabis
  • depression
  • endocannabinoid system
  • rodent models

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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