Defining Cannabinoid
By Alex MacNeil | Budtender
A Cannabinoid by Any Other Name…
A rose by any other name may smell just as sweet, but roses come from family of flowering plants known as Rosaceae. This includes apples, raspberries, hawthorns, and more than 300 species of rose. Cannabinoids are similarly classified. Just as the rosaceae family was named after roses but includes many plants, cannabinoids were named after cannabis but now could refer to many molecules. Along with the variety of types, there are various definitions. This can be confusing at first, so let us shine a light on the situation by exploring phytocannabinoids, endocannabinoids, and synthetic cannabinoids.
THC was the first cannabinoid discovered by Gaoni and Mechoulam in 1964[1]. Devane et al discovered the first receptor for THC in 1988[2]. This was the first hint of a link to the human body’s endocannabinoid system. At this time the term cannabinoids related only to the source plant, cannabis. Through the 1960s we discovered CBN, CBD, CBC, CBG, and various alterations of them. Since all were derived from the cannabis plant there was no need to specify further. We later noted all the cannabinoids started as CBGA, and they were all variations or isomers of CBN. Depending on who you talk to, they may reference any of these as defining facts.
It was later discovered that there are cannabinoid-like molecules in other plants besides cannabis. These are sometimes called cannabimimetics. Echinacea, Apiaceae (the celery, carrot and parsley family), and a particular liverwort are plants known to have cananbinoid-like effects. Specifically, some N-alkylamides, falcarinol, and perrottetinene are the chemicals related to these plants. Beta-caryophyllene is well known by the cannabis community to have cannabinoid-like effects. All of these can be called phytocannabinoids, meaning plant-derived chemicals that activate the endocannabinoid system. The cannabinoids in the cannabis plant also fall under this category. With this expanded definition there’s no need for terms such as ‘cannabinoid-like.’ It should be noted that some of these look very like THC or CBN, but many are quite different.
Through the ‘90s we discovered chemicals inside the body that also activate the cannabinoid receptors. These were called endocannabinoids, meaning cannabinoids from within. At this point the endocannabinoid system was acknowledged and named. Anadamide (AEA), 2-AG, Noladin ether (2-AGE), and N-arachidonoyl dopamine (NADA), to name a few. These don’t all look like THC or CBN and often act very differently, are sometimes much stronger or weaker, or sometimes do not act at all. It’s thought that the ones without any direct action contribute to the entourage effect, just as some non-active phytocannabinoids do.
As ‘canna-phytocannabinoids,’ ‘other-plant-phytocannabinoids’ and endocannabinoids were found, those who study them always wanted to know how they worked. The best way to find out was to make alterations of them and observe the results. This gave rise to synthetic cannabinoids, or chemicals that act on the endocannabinoid system which are entirely synthetic. These have an unpopular reputation for abuse in popular culture, but without them we would be in the dark ages of cannabinoid science and medicine. Many synthetic cannabinoids are weaker or stronger than THC, and one of them, Nabilone, is used in medical applications and is nearly the exact same strength as THC. Some of them are inactive and serve only to block the receptor, such as riboublant. Some, such as the HU family of chemicals, resemble THC. Others are quite divorced from the form we know, such as the JWH family. We’ve even named a receptor-binding site after one of them: CP-50. This is where THC latches on to the CB1 receptor.
So, what is a cannabinoid? In simplest terms it is anything that has effects on the endocannabinoid system. This means it can activate, deactivate, block, or indirectly act on the receptors. A deeper dive into the system might show how some affect the balance of endocannabinoids, or some interact with enzymes that interact with receptors. We will investigate that in a future article.
[1] https://pubs.acs.org/doi/pdf/10.1021/ja01062a046
[2] https://www.ncbi.nlm.nih.gov/pubmed/2848184/