LigandsThe compounds that bind to receptors are called ligands and are categorized by their interaction type:
- Agonists (sometimes called full agonists) are ligands that bind to a receptor and cause it to activate and produce a biological response (see illustration).
- Partial agonists bind to the receptor but only causes a partial effect (see illustration). THC is a partial agonist of both CB1 and CB2 receptors.1, 2
- Antagonists do not exert any effect at the receptor level (see illustration). This means that, for example, in the presence of an antagonist at the receptor, the action of exogenous or endogenous agonists cannot happen.
- Inverse agonists cause an opposite action to that of agonists.
- Allosteric modulators are ligands that, upon binding, make receptors either more or less receptive to the effect (e.g. agonistic) ligand. This effect is called a positive or negative allosteric modulation respectively. It is thought that CBD’s THC-inhibiting effects are due to allosteric modulation by CBD on the CB1 receptor.3 Also, other cannabis compounds, such as terpenes, are thought to give allosteric effects during an interaction of THC with receptors.4
Illustration and caption taken with permission from TRC Pharmacology Database.References:
- Grotenhermen, Franjo (2003). Clinical Pharmacokinetics of Cannabinoids. Journal of Cannabis Therapeutics, 3(1), 3--51.
- Grotenhermen, Franjo (2004). Clinical Pharmacodynamics of Cannabinoids. Journal of Cannabis Therapeutics, 4(1), 29--78.
- Laprairie, R. B.; Bagher, A. M.; Kelly, M. E. M.; Denovan-Wright, E. M. (2015). Cannabidiol is a negative allosteric modulator of the cannabinoid CB 1 receptor. British Journal of Pharmacology, 172(20), 4790--4805.
- Kenakin, Terry P. (2012). Chapter 5 - Allosteric Drug Effects BT - Pharmacology in Drug Discovery. Pharmacology in Drug Discovery (81--103). Academic Press.
- Izzo, Angelo A.; Borrelli, Francesca; Capasso, Raffaele; Di Marzo, Vincenzo; Mechoulam, Raphael (2009). Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends in Pharmacological Sciences, 30(10), 515--527.
- McPartland, John M.; Duncan, Marnie; Di Marzo, Vincenzo; Pertwee, Roger G. (2015). Are cannabidiol and Δ 9 -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. British Journal of Pharmacology, 172(3), 737--753.