Cannabis and its multitudinous effects inspired the discovery of the endocannabinoid system (ECS). [1,2] The ECS is an innate signaling system of receptors, primarily (but not exclusively) cannabinoid type 1 (CB1) and type 2 (CB2), as well as endocannabinoids, primarily anandamide and 2-arachidonoylglycerol (2-AG). This biological system is complex and widespread through the brain, central nervous system, and organs, helping to regulate functions that range from inflammation to cognition. Its purpose in the most general sense is physiological homeostasis. Therefore, the ECS has become a potential target for the treatment of numerous health conditions. [1,2]
Pharmacotherapy can be defined, simply, as treating health conditions with drugs. The ECS is a target for pharmacotherapy from plant-derived compounds as well as, potentially, synthetic compounds. [2] A few of the broad targets of the ECS are briefly summarized below.
Pain & Inflammation
Tetrahydrocannabinol (THC), cannabidiol (CBD), the endocannabinoids, and other cannabinoids have been found to reduce most types of pain (e.g., neuropathic, inflammatory, thermal, etc.). [2] The ECS may even be involved in the therapeutic effects of acetaminophen, and cannabinoids have shown synergistic activity against pain when combined with non-steroidal anti-inflammatory drugs (NSAIDs). [2] The CB2 receptor, located on immune cells, plays a significant role by reducing inflammatory responses. Cannabis has demonstrated efficacy against pain in patients with multiple sclerosis, traumatic nerve injury, and human immunodeficiency virus. Ultimately, the ECS may play a role in countless health conditions involving pain and inflammation. [2]
Metabolism
Stimulating CB1 receptors boosts appetite. [2] THC, a partial agonist at the CB1 receptor, is known for this effect; FDA-approved dronabinol—synthetic THC—is said to promote appetite for 24 hours after administration. Both anandamide and 2-AG also stimulate appetite, and CB1 receptor antagonists (blocking this receptor) reduce appetite. Activity in the ECS appears to be inversely linked to the hormone leptin, the hunger-reducing hormone. It also acts on reward pathways related to consumption.
Therefore, the ECS is a prime target for detrimental weight loss, such as that from wasting diseases, aging, anorexia nervosa, etc. [2] On the other hand, remarkably, cannabis use is associated with a lower prevalence of obesity. This may be due to interactions between the ECS and insulin, the actions of cannabinoids other than THC, and the ECS’ overarching action toward homeostasis (e.g., not promoting food intake in overweight individuals).
Central Nervous System
High density of CB1 receptors across brain areas such as the hippocampus and basal ganglia, as well as the spinal column, indicates that the ECS safeguards the health of the central nervous system. [2] As an example of neuroprotection, THC shields neurons from the damaging effects of excess glutamate receptor activation known as excitotoxicity. Furthermore, cannabinoids help mitigate excitatory glutamate transmission. This protection against excitotoxicity makes the ECS a target for treating epilepsy, Parkinson’s disease, and Alzheimer’s disease.
The ECS is also involved in emotion and mood; THC has been found to boost well-being in normal individuals (although too high doses may reverse this effect). CBD is both an anti-anxiety and anti-psychotic agent. [2] Unlike THC, it is an agonist for serotonin receptors; the neurotransmitter serotonin is fundamental in mood regulation. The ECS is complex, interacting with many other systems, and this unique action of CBD illustrates how certain phytochemicals may be more helpful for certain outcomes.
Other targets worth discussion include (but are not limited to) the cardiovascular, reproductive, and gastrointestinal systems. [2] Indeed, our brief list could fill volumes. Given its encompassing role, it may be fair to say that the ECS is entwined in all disease states.
Image: andreas160578 from Pixabay
References
- Crocq MA. History of cannabis and the endocannabinoid system. Dialogues Clin Neurosci. 2020;22(3):223-228. doi:10.31887/DCNS.2020.22.3/mcrocq. [Impact Factor: 5.397; Times Cited: n/a]
- Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006;58(3):389-462. doi:10.1124/pr.58.3.2. [Impact Factor: 17.814; Times Cited: 1,555 (Semantic Scholar)]
