By Mitchell Colbert
There are nearly a hundred cannabinoids that have been identified in both the cannabis plant and naturally occurring in the human body. There are two main types of cannabinoids, phytocannabinoids (produced by the plant) and endocannabinoids (produced by your body). Cannabinoids affect us and produce medical effects by using the endocannabinoid system, which is a series of receptor sites located throughout the body and the endocannabinoids that trigger those receptors. The endocannabinoid system was evolved nearly 600 million years ago and is found in virtually all animals on earth, other than insects. If it wasn't for our endocannabinoid system, we would be unable to feel the effects of cannabis, and it would be just another weed in the garden.
As of this writing, there have been five endocannabinoids identified in humans; anandamide, 2-arachidonyl glycerol (2-AG), noladin ether, N-arachidonyl dopamine (NADA), and virodhamine. All five of these chemicals are understood to act as neuromodulators, meaning they affect the ways our brains process other chemicals, such as amino acids. Little is known about noladin ether, NADA, and virodhamine, and while more is understood about 2-AG, the bulk of endocannabinoid research is on anandamide, which was the first discovered in 1992.
Anandamide has been nicknamed the bliss molecule and it is your body's natural version of THC, like THC is has a wide variety of medical properties, including euphoria (feeling high). THC and anandamide both activate the CB1 receptor, which causes euphoria; CBD has no interaction with CB1 which is why it is non-psychoactive. Anandamide is what allows a person to feel “high on life” or to get a “runner's high,” and research shows that people who don't have enough anandamide are more likely to suffer from anxiety, and other mood disorders like PTSD. A 2003 study done by GW Pharmaceuticals identified a condition they refer to as “clinical endocannabinoid deficiency,” resulting in people developing migraines, fibromyalgia, IBS, and other conditions. Clearly, a healthy endocannabinoid system is crucial to healthy functioning, which may explain why cannabinoids have been found in breast milk.
Aside from the chemicals that use the endocannabinoid system, there are also receptor sites that those chemicals interact with. The two main type of endocannabinoid receptors are CB1 and CB2 receptors. Both types of receptors are located throughout the body at certain key points; in the central nervous system (CNS), in the immune system, and in the reproductive system. These receptors control everything from basics, like movement, pain regulation and inflammation, all the way up to our higher cognitive functions, including memory and learning. While these receptors are widespread, they are not present in the brain stem, which means that even very high doses of cannabinoids will not stop breathing the way that opiate drugs do at small doses.
CB1 receptors are called that because they were the first discovered and had been believed to be the only endocannabinoid receptors in the CNS, but recent research has shown that CB2 receptors are also present in the CNS. While there had been speculation about other types of receptors in the endocannabinoid system it was not until 2007 that another endocannabinoid receptor had been discovered, the orphan receptor GPR55. This receptor was shown to be activated by both anandamide and virodhamine; the researchers speculated that cannabidiol (CBD) may also interact with GPR55.
Outside of the endocannabinoid system, endocannabinoids and phytocannabinoids have been shown to interact with other types of receptors, such as the 5HT1a receptor, the TrpV1 receptor, and the α2-adrenoceptor. The 5HT1a receptor is critical in the creation and proper function of serotonin, if this receptor is under-active it can lead to the formation of depression and anxiety. CBD has been shown to be an agonist of the 5HT1a receptor, binding to it and activating it, leading to a relief of anxious or depressed feelings. A different phytocannabinoid, cannabigerol (CBG), has been shown to be an antagonist of the HT1a receptor, dampening or blocking the effects of that receptor site, making it harder to activate. The TrpV1 receptor is responsible for our ability to feel scalding heat and pain, regulation of this receptor site can lead to relief of pain and numerous other medical benefits. CBD and THC have both been shown to have interactions with TrpV1, numerous terpenes and other cannabinoids also interact with this protein channel. It would appear that many of the medical effects of cannabinoids are due to their interaction with the TrpV1 receptor, even moreso than the endocannabinoid system itself.