Endocannabinoids are naturally produced in the body. The endocannaboid system operates through the nervous system with roles in several regulatory, physiological, and metabolic processes. They are produced in response to calcium levels in the cells to help stabilize nerve transmissions. The main endocannabinoids are called anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonyl glycerol (2-AG). The endocannabinoids act as activators (“agonists”) of the cannabinoid receptors which are also naturally present in the body.
There are two types of cannabinoid receptors:
CB1R is mostly found in the central nervous system. It modulates several inhibitory and excitatory neurotransmitters, and its activation inhibits anxiety. AEA is a partial agonist and 2-AG a full agonist of CB1R.
CB2R is mostly found on immune cells, and its activation reduces inflammation. AEA is a weak agonist and 2-AG a full agonist of CB2R.
Cannabidiol (CBD) is the main phytocannabinoid in Cannabis besides tetrahydrocannabinol (THC, the intoxicating cannabinoid, which mimics AEA but at higher concentrations can increase anxiety; CBD can reduce the side-effects of THC). In “hemp”, which has negligible THC, CBD is the main cannabinoid.
Unlike THC, which activates the endocannabinoid receptors, CBD binds with the proteins that carry AEA and 2-AG to the enzymes that break them down. That prevents the breakdown of the endocannabinoids AEA and 2-AG and serves to reduce anxiety and depression, respectively. CBD also has strong analgesic and anti-inflammatory properties. Its half-life is ~9 hours.
CBD has other actions and consequent effects as well:
- CBD binds with CB1R as an inverse agonist (deactivator), reducing inflammation.
- CBD binds with 5-hydroxytryptamine (5-HT, serotonin) 1A receptor, reducing depression.
- CBD binds with transient receptor potential cation channel subfamily V member 1 (TrpV1, vanilloid receptor 1, capsaicin receptor) as an antagonist (blocker), reducing pain.
- CBD binds with peroxisome proliferator–activated receptor (PPAR) gamma, reducing inflammation.
- CBD has direct antioxidant effects.
In addition, the terpenes in Cannabis have anti-inflammatory and analgesic properties.
Cannabidiol in Pubmed-indexed science publications
