Endocannabinoid System and Exogenous Cannabinoids in Depression and Anxiety: A Review

Abstract

Background: There is a growing liberalization of cannabis-based preparations for medical and recreational use. In multiple instances, anxiety and depression are cited as either a primary or a secondary reason for the use of cannabinoids. Aim: The purpose of this review is to explore the association between depression or anxiety and the dysregulation of the endogenous endocannabinoid system (ECS), as well as the use of phytocannabinoids and synthetic cannabinoids in the remediation of depression/anxiety symptoms. After a brief description of the constituents of cannabis, cannabinoid receptors and the endocannabinoid system, the most important evidence is presented for the involvement of cannabinoids in depression and anxiety both in human and from animal models of depression and anxiety. Finally, evidence is presented for the clinical use of cannabinoids to treat depression and anxiety. Conclusions: Although the common belief that cannabinoids, including cannabis, its main studied components—tetrahydrocannabinol (THC) and cannabidiol (CBD)—or other synthetic derivatives have been suggested to have a therapeutic role for certain mental health conditions, all recent systematic reviews that we report have concluded that the evidence that cannabinoids improve depressive and anxiety disorders is weak, of very-low-quality, and offers no guidance on the use of cannabinoids for mental health conditions within a regulatory framework. There is an urgent need for high-quality studies examining the effects of cannabinoids on mental disorders in general and depression/anxiety in particular, as well as the consequences of long-term use of these preparations due to possible risks such as addiction and even reversal of improvement.

Pharmacovigilance of unlicensed cannabidiol in European countries

“…These symptoms, together with temporary diarrhea and reduction of appetite were confirmed by other studies, but the long-term effects of CBD in epileptic patients are not definitively known (Laux et al, 2019;Wu et al, 2022). This is the first pharmacovigilance report based on real-world data on adverse reactions related to the consumption of unlicensed CBD products and, despite the fact that information is limited to the The detection of mental disorders at the top of reaction groups of serious adverse reactions to CBD could be amazing since this compound has been more times cited as a possible chemical to use to treat psychiatric disorders (Calapai et al, 2019;Hasbi et al, 2023;Telch et al, 2022). A possible explanation for mental disorders could be that CBD is a full agonist toward the serotonergic 5-HT1A receptor (Russo et al, 2005).…”

“…The detection of mental disorders at the top of reaction groups of serious adverse reactions to CBD could be amazing since this compound has been more times cited as a possible chemical to use to treat psychiatric disorders (Calapai et al, 2019; Hasbi et al, 2023; Telch et al, 2022). A possible explanation for mental disorders could be that CBD is a full agonist toward the serotonergic 5‐HT1A receptor (Russo et al, 2005).…”

Cannabis Science and Therapeutics: An Overview for Clinicians

“…The role of the ECS in modulating mood is welldocumented in animal studies. 44 Anxiolytic effects are mediated by the CB1 receptor. The effect of CB1 activation appears to be biphasic, with low doses of exogenous CBs providing positive benefits and higher doses being anxiogenic.…”

Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviors: effects of in vitro cannabidiol administration

“…Cannabidiol (CBD), a phytocannabinoid extracted from the cannabis plant, is a potential antidepressant (Atalay et al, 2019). There is evidence that CBD may improve clinical depression and clinical anxiety (Martin et al, 2021), although not all studies show positive results (Hasbi et al, 2023). Some, but not all, animal models of depression show that cannabinoids have antidepressive effects (Hen-Shoval et al, 2018;Hasbi et al, 2023).…”

“…There is evidence that CBD may improve clinical depression and clinical anxiety (Martin et al, 2021), although not all studies show positive results (Hasbi et al, 2023). Some, but not all, animal models of depression show that cannabinoids have antidepressive effects (Hen-Shoval et al, 2018;Hasbi et al, 2023). CBD has a lower affinity for CB2 receptors than anandamide (AEA), 2-arachidonoylglycerol (2-AG), and delta-9tetrahydrocannabinol (THC) (Pertwee et al, 2007;Raich et al, 2021), but possesses antiinflammatory and antioxidative properties, such as by inhibiting the production of proinflammatory cytokines and reactive oxygen species (Atalay et al, 2019).…”