CB1 and CB2: Cannabinoid Receptors of the Brain and Body

Key takeaways.

When we open up the scientific conversation about cannabinoids, we typically talk about CBD and THC and how they affect the brain differently. Cannabinoids are often spoken about in terms of how they affect different cannabinoid receptors, such as the CB1 and CB2. 

When learning cannabinoid science, it’s not uncommon to hear things like “THC has a great affinity for the CB1 receptor” and that “CBD has no real affinity for CB receptors”. CB receptors are essentially the vehicles by which cannabinoids move through the body and affect changes in the human body. 

Although CB1 and CB2 receptors are part of the same endocannabinoid system of the human body, they are distributed differently and their excitement causes different biological responses. While the CB1 receptor is primarily distributed in the brain, the CB2 receptor is primarily distributed in the gastrointestinal and immune system. 

In this article, we’re having a look at the difference between CB1 and CB2 receptors, their locations, and what kind of responses they are a part of.

The CB1 receptor.

(Image from Zou and Kumar)

The CB1 receptor is the prominent type of cannabinoid receptor in the central nervous system — a.k.a. The brain. In fact, the brain was the place that the CB1 receptor was first discovered. Since its discovery, we’ve also come to learn that the CB1 receptor is the most widely expressed GPRC (a group of cell receptor proteins) receptor in the brain. Recent research has demonstrated that CB1 receptors also live on the surface of neuronal mitochondria. 

Because the CB1 receptor likes to hang out in the brain, it comes as no surprise that many of its biological responses are of a nervous kind. The CB1 receptor is the one that lovingly receives THC and causes the cognitive effects we now call “high”.CB1 receptor activity has effects on learning, memory, cognition, motor control, appetite, anxiety and depression, sleep, reward and addiction and even more. Not every excitation of the CB1 receptor will affect all of these functions, but the CB1 receptor is involved, at least in part, with many aspects of these functions. 

The CB1 receptor is also modestly distributed around the rest of the body. It can be found in the liver, the reproductive system, skeletal muscle, and the gastrointestinal tract. The CB1 receptor is also found as a part of the enteric nervous system — the nervous system that lives in your gut! In the gastrointestinal tract, the CB1 receptor affects GI motility and energy metabolism. 

The CB2 receptor.

The CB2 receptor doesn’t like to be stationary like the CB1 receptor. Instead, the CB2 receptor likes to hang out on the surface of white blood cells which travel around the body and through lymph nodes. Therefore, CB2’s primary role is in the immune system. It’s generally understood that the CB2 receptor in the immune system regulates cytokine release. 

CB2 is also widely distributed through the gastrointestinal tract, where it’s thought to regulate gastrointestinal inflammation. This makes the CB2 receptor a huge target for gastrointestinal diseases such as Crohn’s disease and other inflammatory bowel diseases.

The CB2 receptor has a big role to play in inflammation all around the body, and clinical application of cannabis seeks to capitalise on this role of the CB2 receptor. Arousal of the CB2 receptor doesn’t cause a cognitive effect the way CB1 does, and that also makes it a great therapeutic target for many kinds of disorders.

Agonism and antagonism.

Cannabinoid receptors can be affected in a lot of ways. Many compounds from within (endogenous cannabinoids) and without the body (phytocannabinoids from cannabis) can stimulate, switch off, or cause the reverse effect on a cannabinoid receptor. These actions are called agonism, antagonism, and reverse agonism. 

THC is a full agonist at the CB1 receptor. It means that when THC binds to the CB1 receptor, it activates it, causing a cascade of events. CBD, on the other hand, may be a non-competitive antagonist at both the CB1 and CB2 receptors. It means that when CBD binds to the receptor, it inhibits the response typically caused by the CB receptor. 

Finally, certain chemicals can be inverse agonists. These are compounds that, when bound to the receptor, cause the inverse effect that the receptor would typically cause. 

Cannabinoid receptors are integral parts of the endocannabinoid system, and are key to the signalling process of the ECS. The more we learn about them, the more it makes sense why cannabis is a potent medicine for so many. The puzzle into understanding cannabis, the human endocannabinoid system, and how it’s all integrated is finally coming together through the understanding of different cannabinoid receptors.