Overview of biological functions

Humans and animals alike are made of complex regulatory and control systems modulating the basic functions as befitting a biological entity. The endocannabinoid system (ECS) is known to play principal roles in memory formation, mood regulation, metabolic process control, glucose metabolism, and the brain reward system. The point of primary interest in the endocannabinoid system is perhaps its production and deactivation of endocannabinoids—lipid mediators that activate the cannabinoid receptors (CRs).

Endocannabinoids are structurally complex and can be made of amides, esters, and ether derivatives of long-chain polyunsaturated fatty acids. Unlike other biological mediators involved in cell signaling, endocannabinoids are only produced on demand from lipid constituents of the cells, and their actions are limited to the intracellular and intercellular environment. Compared to cannabidiol (CBD) and other cannabis-derived cannabinoids, endocannabinoids are relatively unstable with a short-half-life and produce no significant systemic action. Endocannabinoids are degraded by the enzyme fatty acid amino hydrolase (FAAH). Alternatively, endocannabinoids can also be deactivated by oxidation reactions initiated by cyclooxygenase-2 (COX-2), creating prostanoids—bioactive molecules with no action on the CRs—as a metabolite.  

Theoretically, the ECS provides an exploitation point for the development of drugs that can mimic the actions of the endocannabinoids on the cannabinoid receptors. If developed, these drugs and latch on to the receptors, activate a desired cell-to-cell signaling and produce an effect that can mitigate the symptoms of chronic human diseases. The degradation pathways can also be therapeutically exploited to prolong the effects of the endocannabinoids or synthetic alternatives. 


Cannabinoid receptors

The cannabinoid receptors (CRs) provide biological action points for the endocannabinoids on numerous target organs where they are present. Researchers have identified two main receptors of the endocannabinoid system (ECS) characterized as membrane-bound G-protein receptors. 


  • CB1 receptors

The CB1 receptors are widely distributed and are readily found in the central nervous system (CNS), particularly in the brain’s mesocorticolimbic system, the spinal cord, and the peripheral neurons—with significant prominence on gamma-aminobutyric releasing neurons and glutaminergic-releasing hormones. This receptor is generally associated with membrane microdomains that modulate its signaling pathways. Depending on the region where it is found, the characteristics, content, distribution, and arrangement of the CB1 receptor vary. Cortical and hippocampus CB1 receptors are the target of many medical researches due to their positive cholecystokinin interneurons. Interspersed in different regions of the brain, including cortex, basal ganglia, cerebellum, hippocampus, ventral striatum, and glial elements, the CB1 are potential targets in the management of CNS disorders and neurodegenerative diseases. 


  • CB2 receptors

Unlike the CB1, CB2 receptors are distributed mainly in the lower levels of the central nervous system. The expression of this receptor is more in immune-modulating cells, the peripheral tissues, vascular elements, and the microglia. The presence of CB2 receptors in immune-modulating cells has prompted research inquiries into possible effects of cannabinoids on autoimmunity. A publication of the Journal of Neurochemistry reported that the expression rate of CB2 receptors on microglial cells in response to an inflammatory stimulus is significantly increased. This observation suggests that CB2 receptors are important in cellular inflammation reactions. Other receptors of the endocannabinoid system affecting minor biological actions include PPRA’s and Transient Receptor Potential channels (TRP).


Physiological roles of the endocannabinoid system

  • Roles in the nervous system

Physiological roles of the cannabinoids on the brain, spinal cord, and the peripheral nervous system is no doubt the most interesting focus of neurochemical research. Reports inspired by different anecdotal evidence have suggested a relationship between the ECS and functions of the nervous system, including memory formation and the pathology of neurodegenerative diseases, especially Parkinson’s disease and seizure disorders. 


In 2009, a research review published by Current Topics in Behavioral Neurosciences examined the roles of the ECS on learning and memory formation with a special focus on the fine-tuned regulation of neural transmission by the system. Reports from the investigation confirmed early suspicions about the roles of cannabinoids on memory formation. There are other reports of neurologic alterations as a result of dysfunctions of the ECS. 


  • Roles in obesity 

Glucose metabolism and energy balance regulation are known physiological roles of the endocannabinoid system. CB1 receptors, as the mediating receptors for these functions, are the target of pharmacological therapy approaches for the management of type 2 diabetes and obesity. Activation of the CB1 receptors increases food intake and regulates the hypothalamic function of appetite regulation. Most importantly, this activation influences the brain reward system and increases the human feeling to seek more. Overactivation of these receptors leads to obesity. 

A report published in the International Journal of Obesity and Related Metabolic Disorders detailed the observation points in research focused on the relationship between CB1 receptors and the onset of obesity in mice. This research confirmed that CB1 receptor knockout in mice leads to leanness and resistance to diet-induced obesity in mice. By extension, it is expected that the inhibition of CB1 receptors in humans can be beneficial in the management of obesity, type 2 diabetes, and other related metabolic disorders. 


  • Roles in the cardiovascular system

Cannabinoid receptors are widely distributed in the cardiovascular system, where they affect complex transient actions on the vasculature and the myocardium. As observed in cannabis smokers, the acute effect of a smoking session includes increased heart rate with no significant changes in blood pressure. These actions are mediated by the activation of the CB1 receptors. Activation of these receptors in the cardiovascular system has also been proven to regulate blood pressure and aid in vasodilation and cardiac contractility.


  • Roles in cancer management

The effects of the endocannabinoid system on the management of cancer are better explained with the observation that cannabidiol (CBD) acts on the cannabinoid receptors to relieve the unwanted symptoms of chemotherapy in cancer patients. Endocannabinoids are known to relieve cancer-induced nausea and vomiting, induce cancer cell death, stimulate appetite, and improve the prognosis of cancer. However, endocannabinoids are too unstable to effect prolonged action on cancer management. Research inquiries are focused on developing synthetic compounds that can mimic the effects of the endocannabinoids on the CB receptors for a prolonged duration.   

Receptor activation and blockage in the endocannabinoid system can lead to numerous physiological effects. There are research reports detailing the roles of this system on pain regulation, stress control, reproduction, and gastrointestinal functions.  



Ian Parkes

Ian has been writing for a number of high growth industries for the past decade. Having plied his trade in the craft beer industry, Ian drew parallels between that and the world of CBD and soon became fascinated. Ian enjoys writing about innovation in the industry, particularly as it relates to the development of the leading brands.

See all posts by Ian Parkes

Participate in CBD Research

CBD World News is part of an active community, working to enhance our understanding of the benefits of CBD. You can become an active part of that community too, by taking part in our collaborative research. We are interested in finding out who is using CBD, how it is used, and what it is used for?

Taking part in this research will help bring the good word of CBD to life and help people all over the world discover the benefits of cannabinoids.