Abstract
The endocannabinoid system (ECS) is ubiquitous in most human tissues, and involved in the regulation of mental health. Consequently, its dysregulation is associated with neuropsychiatric and neurodegenerative disorders. Together, the ECS and the expanded endocannabinoidome (eCBome) are composed of genes coding for CB1 and CB2 cannabinoid receptors (CB1R, CB2R), endocannabinoids (eCBs), and the metabolic enzyme machinery for their synthesis and catabolism. The activation of CB1R is associated with adverse effects on the central nervous system (CNS), which has limited the therapeutic use of drugs that bind this receptor. The discovery of the functional neuronal CB2R raised new possibilities for the potential and safe targeting of the ECS for the treatment of CNS disorders. Previous studies were not able to detect CB2R mRNA transcripts in brain tissue and suggested that CB2Rs were absent in the brain and were considered peripheral receptors. Studies done on the role of CB2Rs as a potential therapeutic target for treating different disorders revealed the important putative role of CB2Rs in certain CNS disorders, which requires further clinical validation. This review addresses recent advances on the role of CB2Rs in neuropsychiatric and neurodegenerative disorders, including, but not limited to, anxiety, depression, schizophrenia, Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD) and addiction.
Highlights
With the significant progress and advances in cannabis and cannabinoid research, there is a renewed focus and interest in targeting components of the endocannabinoid system (ECS) in central nervous system (CNS) disorders, even in children, and in neurodegenerative disorders
The debunking of the myth that CB2Rs are only found in the “periphery” and the absence of intoxicating effects of these receptors significantly increased the interest in the investigation of these receptors as a therapeutic target in neuropsychiatric and neurodegenerative disorders
We cannot completely be satisfied with the partially effective treatments for most of these disorders, and more research is warranted for new therapeutic targets using novel strategies, including artificial intelligence (AI), that might have better prediction and therapeutic outcomes with minimal adverse effects
Summary
With the significant progress and advances in cannabis and cannabinoid research, there is a renewed focus and interest in targeting components of the ECS in CNS disorders, even in children, and in neurodegenerative disorders. The recognition and knowledge regarding cannabinoids which lack CNS intoxicating effects is adding to the growing awareness of the putative role of CB2Rs in different disorders [2]. In this narrative review method, we have summarized our pivotal research contribution to the discovery of the CB2Rs, with a focus on the preclinical and clinical work of other researchers using cannabis, cannabinoids, CB1R, CB2R, and cannabinoid receptor genetics in neurological and psychiatric disorders for PubMed searches.
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