Receptor molecules like cannabinoids and terpenes fit into special receptors within the endocannabinoid system, or ECS. A researcher or doctor would say that molecules like CBD activate particular cannabinoid receptors. These receptors, called CB1 and CB2, work like a lock and key when flooded with cannabinoids, after a patient applies topically or ingests.
Receptor Expression--One patient may overexpress a receptor like CB1 (meaning they have more receptors than average) and, as a result, be very sensitive to a cannabinoid like CBD. Other patients may underexpress a receptor like CB2, meaning they may be less sensitive to the therapeutic effects of a cannabinoid like CBD and may need to consume it in greater quantities or add other cannabinoids and terpenes to the mix, especially those that target other receptors, like CB1.
This targeting is formally called a binding affinity. Some molecules may feature a relatively low binding affinity that offers poor or moderate efficacy for a patient, while other pairings feature a very strong affinity that, when combined with cannabinoids from high-quality plants, can result in superb medical benefit or psychoactive effects.
Receptor expression pertains not only to variations among individuals, but also to the density of a particular type of receptor within a region of the body. For example, a study published in 2010 in the British Journal of Pharmacology provided further evidence that receptors vary in the density with which they appear in various parts of the body, mostly the brain, central nervous system, and immune system.
“CB1 receptors are highly expressed in the central nervous system (CNS), with low to moderate expression in the [peripheral nervous system].”
Receptors can accommodate a variety of molecular structures, so it’s not a situation of CB1 receptors, for example, accommodating only the CBD molecule. These molecular parking spots may have a higher binding affinity for CBD than most other cannabinoids and terpenes, but other molecules may also bind with this receptor, with a variety of affinities.
According to a 2012 study published in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry, a single receptor type can recognize and bind with multiple varieties of molecules. Due to the dearth of research that has been conducted regarding the human endocannabinoid system and is interaction with phytocannabinoids from herbs like cannabis, experts and scientists can currently only speculate regarding the complexity and breadth of this system that is so critical for human health — and is present in all mammals (this is why cannabis studies on primates and rodents yield data that can be effectively extrapolated to humans).
Reported the study: “The complex molecular architecture of each of the cannabinoid receptors allows for a single receptor to recognize multiple classes of compounds and produce an array of distinct downstream effects.”
Many researches and scientists speculate that other receptors, beyond CB1 and CB2, may easily exist. A detailed understanding about how cannabinoids and terpenes interact with currently unknown receptor types in the endocannabinoid system could potentially result in cannabinoid therapies targeted at particular diseases and conditions. Until this research is conducted, however, those considering cannabis to treat their condition must rely mostly on anecdotal evidence provided by fellow patients.
The 2012 study cited above concluded that additional cannabinoid receptors, which it labels “sites of action,” likely exist.