The endocannabinoid system in mental disorders: Evidence from human brain studies

Abstract

Mental disorders have a high prevalence compared with many other health conditions and are the leading cause of disability worldwide. Several studies performed in the last years support the involvement of the endocannabinoid system in the etiopathogenesis of different mental disorders. The present review will summarize the latest information on the role of the endocannabinoid system in psychiatric disorders, specifically depression, anxiety, and schizophrenia. We will focus on the findings from human brain studies regarding alterations in endocannabinoid levels, cannabinoid receptors and endocannabinoid metabolizing enzymes in patients suffering mental disorders. Studies carried out in humans have consistently demonstrated that the endocannabinoid system is fundamental for emotional homeostasis and cognitive function. Thus, deregulation of the different elements that are part of the endocannabinoid system may contribute to the pathophysiology of several mental disorders. However, the results reported are controversial. In this sense, different alterations in gene and/or protein expression of CB1 receptors have been shown depending on the technical approach used or the brain region studied. Despite the current discrepancies regarding cannabinoid receptors changes in depression and schizophrenia, present findings point to the endocannabinoid system as a pivotal neuromodulatory pathway relevant in the pathophysiology of mental disorders.

Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

“…Several models are more susceptible to the effects of cannabinoids such as THC and CBD on schizophrenia-relevant behaviours, and this is accompanied by complex changes in cannabinoid, glutamatergic, serotonergic and GABAergic receptor systems. Considering changes to these systems have all been reported in schizophrenia [208,[208][209][210][211], these findings not only validate the models used, but indicate how changes in these systems are relevant to both schizophrenia and drug susceptibility. Changes to specific receptor systems and subunits indicates which targets are specifically affected by drug exposure in schizophrenia, increasing our understanding of interactions between these disorders and potentially providing targets for future pharmacotherapies specifically designed to treat addiction in schizophrenia.…”

Inner Engineering Practices and Advanced 4‐day Isha Yoga Retreat Are Associated with Cannabimimetic Effects with Increased Endocannabinoids and Short‐Term and Sustained Improvement in Mental Health: A Prospective Observational Study of Meditators

“…Deficiencies in anandamide can be associated with acute stress [25] and increased pain [26]. Studies have related depression and anxiety to the expression and/or functionality of cannabinoid type 1 (CB1) receptors and FAAH in brain areas belonging to the amygdala-hippocampal-corticostriatal neural circuit, especially the frontal cortex in depression and the amygdala in anxiety disorders [13]. Increasing patients' anandamide levels is a potential solution for many ailments including depression [27,28], fibromyalgia [29,30], inflammatory bowel disease [31][32][33], and cancer [34,35].…”

“…Other eCBs include 1-arachidonoylglycerol (1-AG), docosatetraenoylethanolamide (DEA), and oleoylethanolamide (OLA) [12]. Serum levels of both anandamide and 2-AG may be reduced in patients with depression and anxiety, and the eCB system plays a fundamental role in emotional homeostasis [13]. We hypothesized that eCBs may be involved in the underlying mechanisms leading to the beneficial effects of meditation.…”

Endocannabinoid System Components as Potential Biomarkers in Psychiatry

“…The ECS is one of the most widely distributed neurotransmitter systems in the human brain, with a critical neuromodulatory role that motivates the interaction with other neurotransmitter and neurohormonal systems (61). Accumulating evidence points out the pivotal role of the ECS in the regulation of cognitive and behavioral functioning, suggesting its therapeutic potential in psychiatry (9,11,62). Furthermore, it is worth to mention that psychiatric disorders are accompanied by disturbances in the ECS components, as detailed below.…”