CB1 Receptors: The Endocannabinoid System’s Catcher’s Mitts For THC

CB1, short for Cannabinoid Receptor 1, is the name of a molecule-sized docking station on the membranes of nerve cells throughout the brain, gut and to a lesser degree, the entire body. CB1 receptors are the most studied of the neuro-receptors that make up the endocannabinoid system, the neuro-signaling system that interacts with the cannabinoids found in the cannabis plant to produce its therapeutic and recreational effects.

The CB1 receptor is a G protein-coupled receptor (GPCR). This means it is built from the same base protein molecule that is the foundation of thousands of other similar nerve receptors in the body, each of which has its own special job in keeping you functioning day-to-day.

The atoms in a generic G-protein coupled receptor form a ring shape that acts as an entrance through the cell membrane. Build on top of this ring are other atoms that make the receptor unique — CB1 receptors rather than, say, histamine receptors, which are implicated in allergic reactions and triggering inflammation. Both are GPCRs, but the shape of the openings dictates which nerve signaling chemical fits in there.

The CB1 receptor acts as a lock, and the keys that fit in it are the body’s endocannabinoid neurotransmitters, called its “ligands.” In the case of CB1, its neurotransmitter ligands are anandamide (AEA) and 2-AG, the more abundant but less-studied endocannabinoid.

Your body naturally produces anandamide, and it’s been shown to regulate appetite, mood, inflammation response and stress response — a huge proportion of all the targets of pharmaceutical research.

THC, or Delta-9 tetrahydrocannabinol, is shaped a lot like anandamide. THC will activate the CB1 receptors, but in not quite the same way as anandamide because it’s a slightly different molecule. And on the molecular level, slight differences in structure translate to large differences in properties and effects.

THC is known as a “partial agonist” of the CB1 receptor, meaning it fits in the lock, but can’t turn the bolt all the way. So when you consume cannabis, it is activating the CB1 receptors by flooding them with THC so more than normal are activated for a longer period of time, and they are activated in a different way than with the body’s own endocannabinoids.

As a result, you experience a shift in mood and perception known colloquially as a “high”.

The reason THC, cannabidiol (CBD) and other molecules in the cannabinoid family (called phytocannabinoids when found in plants) have so much potential to treat so many conditions is that the endocannabinoid system is responsible for regulation of most other neural signaling processes. One prominent neuroscientist called the endocannabinoid system the “traffic cop of the nervous system.”

Did you know? Cannabinoids found in the body are called endocannabinoids. Cannabinoids found in plants like cannabis are called phytocannabinoids.

One interesting fact about the human endocannabinoid system is that it squirts out neurotransmitters between neurons to carry impulse messages, but it does it backwards compared to most other nerve signaling systems. This is called “retrograde signaling.” Scientists theorize this is how the ECS regulates nerve impulses, by traveling backward across the synapse (the tiny space between nerve cells) to tell the cell to stop or adjust the transmission of other neurotransmitters.

Another interesting fact about the endocannabinoid system is that endocannabinoids (as well as THC and CBD) are fat-soluble as opposed to water-soluble. Neurologists for decades thought fat-based neurotransmitters were impossible because cell membranes (where CB1 receptors are found) are made of fat. This means instead of fitting into particular receptors, a hypothetical fat-based molecule would pass willy-nilly in and out of the fat-based membranes of cells, wreaking chemical havoc on the nervous system.

This isn’t the case with the endocannabinoid system, however: It works just fine with fat-soluble neurotransmitters. But, because of the problem of cell permeability, the body has to clean up the used cannabinoids really fast to keep them from bouncing around and messing with brain processes they’re not supposed to. 

Enzymes called FAAH, MAGL and potentially others snatch up the used cannabinoids — whether they’re your body’s or from pot — and begin metabolizing them so that they aren’t tonically exciting your CB1 receptors.

The CB1 receptor has its own gene in our DNA called CNR1. CNR1 codes for the protein that forms the CB1 receptor. Diseases associated with mutations of the CNR1 gene include anxiety and a propensity toward forming a cannabis habit. CNR1 “mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain,” according to the gene summary at GeneCards.org.