Modulation of Endocannabinoid System Components in Depression: Pre-Clinical and Clinical Evidence
International Journal of Molecular Sciences May 15, 2022 DOI: 10.3390/ijms23105526 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression |
| Citations | 42 |
| Key findings | Argues that the endocannabinoid system may be involved in the etiology of depression, citing reported deficits in ECS components in depressed patients and in animal models of depression, and proposes that understanding how cannabinoids affect these components could inform diagnosis and treatment. The authors note that many patients do not respond to monoaminergic first-line medications and that remission rates are low. |
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.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cited by 3
- Modulation of the endocannabinoid system by (S)-ketamine in an animal model of depression. Pharmacological Research 2025
- Endocannabinoids, depression, and treatment resistance: Perspectives on effective therapeutic interventions Psychiatry Research August 18, 2025
- CB1R-dependent mitochondrial biogenesis may contribute to the antidepressant effects of esketamine in a chronic variable stress male mouse model. Neuroscience July 27, 2026
Cites 14
- Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis Proceedings of the National Academy of Sciences December 13, 2005
- Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review BMC Psychiatry January 16, 2020
- Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: A systematic review and meta-analysis The Lancet Psychiatry October 28, 2019
- Cannabinoids: from pot to lab International Journal of Medical Sciences August 6, 2018
- A naturalistic examination of the perceived effects of cannabis on negative affect. Journal of Affective Disorders August 1, 2018
and 9 more in the library