Everything you wanted to know about cannabinoids: What are cannabinoids?

There was a time, not too long ago, that I was not doing science. Because I remember that time, I also remember how completely ignorant I was of science.

This is no more apparent than the science of cannabinoids, i.e., the stuff in marijuana. My only knowledge of cannabinoids was that marijuana got you high and cured every disease. Having spent five years researching THC, I learned that there was a much richer, deeper story than that.

You see, the term cannabinoids, itself, is not operationally defined very easily. Delta9-tetrahydrocannabinol (THC) is the main psychoactive constituent (not ingredient) of marijuana. However, there are many, many more “phytocannabinoids” contained in marijuana, which have no known pharmacological actions. Cannabidiol, another constituent of marijuana, also has no psychoactive properties, and is called non-THC oil (or so I see on the internet). Cannabidiol (CBD) is also found in Sativex along with THC, and has some pharmacological actions distinct from THC.

There are also endogenous cannabinoids, which are molecules synthesized within our body that act as part of an endogenous cannabinoid system. They are referred to as cannabinoids because they bind to cannabinoid receptors, which currently include cannabinoid receptor 1 (CB1) and 2 (CB2). These two endogenous cannabinoids are anandamide (AEA) and 2-arachidonoyl glycerol (2-AG).

In one sense, cannabinoids are defined as constituents of marijuana, even though they have no pharmacological efficacy that is known. In another sense, they are those molecules that bind to CB1 and CB2 receptors. In a third sense, cannabinoids are also classified by their actions in a preclinical behavioral battery known as the “tetrad.” The tetrad is composed of four behavioral measures: catalepsy, locomotor inhibition, antinociception and hypothermia. In rodents, THC, other synthetic cannabinoids and endogenous cannabinoids (2-AG more so than AEA) produce these four behaviors.

When I was testing the effects of THC, I carried out tetrad studies. I can tell you that the tetrad is so repeatable that it was nice to have such a positive control. In one sense, it should be a law that THC produces the tetrad in rats or mice. Therefore, when someone refers to THC as a cannabinoid, ask them what a cannabinoid is, and you may be surprised by the answer. For now, this will be my first post on this subject. I apologize for the brevity, but I would like to get input on what people desire to know about THC/cannabinoids.