Mechanism of Action
Cannabinoids in General
For a more comprehensive guide to all cannabinoids, their potential therapeutic targets and the mechanisms by which they are thought to operate please visit our R&D mechanism of action section by clicking here.
The way in which cannabinoids such as THC exert their effects on the human body is known as their “mechanism of action”. This has recently become clearer with the discovery of two cannabinoid receptors CB1 and CB2 together with that of a chemical called “anandamide”. Anandamide is an endogenous ligand, which literally means that it occurs naturally within the body (endogenous) and is a binding agent or “ligand”. The full name of anandamide is arachidonoyl ethanolamide but it was nicknamed anandamide after the Sanskrit word for bliss “ananda”i. Anandamide has its effect by inhibiting cyclic AMP (part of the cellular energy gerneration process), through G-protein coupling in target cells, which cluster in areas of the central nervous system that mediate painii, memoryiii, and other key functions.
Preliminary tests of pharmacology and behavioural activity support the similarity of anandamide to THCiv. Both anandamide and THC bind weakly to the cannabinoid type one (CB1) receptors, which are found in the brain and are called partial agonistsv,vi.In contrast, cannabidiol (CBD) has little activity at CB1 but greater activity at the cannabinoid type 2 receptors (CB2) that are mostly located in the periphery, in lymphoid tissuesv. CB1 receptor distribution and THC binding affinity at CB1 differ between humans and rodents, which underscores the importance of conducting human clinical trialsvii. Both THC and CBD are neuroprotective antioxidants that have been shown to inhibit NMDA-mediated excitotoxicity under conditions of traumatic head injury, stroke and degenerative brain diseasesviii.
The discovery of the endocannabinoid systemviiihas provided new insights into a neuromodulatory scheme that may provide better explanations of, and treatments for, a wide variety of previously poorly treatable, often painful disordersvi,x.
It has recently been demonstrated that CBD also stimulates vanilloid pain receptors (VR1), inhibits uptake of the anandamide, and weakly inhibits its breakdownxi. These new findings have important implications in elucidating the pain-relieving, anti-inflammatory, and immunodulatory effects of CBD.
The combination of THC, CBD and essential oils in cannabis-based medicinal extracts may produce a therapeutic preparation whose benefits are greater than the sum of its partsxii.
ii. Herkenham MA. Localization of cannabinoid receptors in brain: relationship to motor and reward systems. In: Korman SG, Barchas JD, editors. Biological Basis of Substance Abuse. London: Oxford University; 1993. p. 187-200.
v. Showalter VM, Compton DR, Martin BR, Abood ME. Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): identification of cannabinoid receptor subtype selective ligands. J Pharmacol Exp Ther 1996;278(3):989-99.
vii. McPartland JM, Glass M, Pertwee RG. 2007. Meta-analysis of cannabinoid ligand binding affinity and cannabinoid receptordistribution: interspecies differences. British Journal of Pharmacology 152:583-589.
xi. Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol 2001;134(4):845-52.