The CB1 receptor is one of the two most studied receptors of the Endocannabinoid System (ECS); the other being the CB2 receptor. The CB1, in full, is Cannabinoid Receptor type 1. CB1 receptors alongside the CB2 and their other counterparts in the ECS help maintain homeostasis; CB1 contributes to the modulation of our metabolism, reproduction, sleep, etc.
CB1 receptors are found in the central nervous system, especially in the basal ganglia of our brains. They are also found in the cerebellum, gonads, eye, connective tissues and some glands. However, they are not in the medulla oblongata, which is why CB1 activation via Cannabis use rarely leads to issues of the respiratory or cardiovascular system—the medulla oblongata controls our cardiovascular and respiratory systems.
Activation, Structure, and Mechanism of CB1 receptors
CB1 receptors are G protein-coupled receptors (GPRCs). The receptors are encoded in our DNA by the CNR1 gene. However, due to our human differences and mutation, we tend to have varying versions of the CNR1 gene. This difference has an effect on how each person responds to cannabinoids—the substances that activate the CB1 receptors.
Cannabinoids activate CB1 receptors by acting as a key, while a CB1 receptor is in the form of a lock. In this context there are two kinds of cannabinoids:
- Endocannabinoids are produced in our bodies, with the major ones being Anandamide (AEA) and 2-arachidonoglycerol (2-AG).
- Phytocannabinoids are from plant sources and the two main ones are Cannabidiol (CBD) and Tetrahydrocannabinol (THC).
These main sources of phytocannabinoid are two of the most popular compounds extracted from the hemp plant.
Its Role in the ECS
The major role of CB1 is regulating the release of neurotransmitters including glutamate, dopamine, and serotonin - thus reducing pain, regulating sleep and improving our appetite.
CB1 and Pain
When cannabinoids bind to CB1 receptors they cause different actions including the inhibition of neurotransmitters, activation of MAP kinase, activation of potassium channels, and deactivation of Calcium voltage-gated channels. This series of actions leads to our relief from the sensation of pain (nociception), and others.
CB1 receptors, being presynaptic receptors, have been shown to facilitate antinociceptive (inhibit pain sensation) effects in our body, when activated. The receptors have done these in the cases of acute pain, chronic pain, neuropathic pain, postoperative pain, etc.
People suffering from conditions characterised by intense pain such as endometriosis, PTSD, Osteoporosis, Fibromyalgia, migraine and arthritis have relied on the ability of their CB1 receptors to attenuate their pain, hence they seek hemp-derived substances like Cannabidiol to activate the CB1 receptors.
CB1 and Brain Aging
Aging, including brain aging, is increasingly connected with neurodegenerative diseases and cognitive inabilities. To understand how CB1 receptors may help when activated, a study showed how mice were experimented upon. Mice with the CNR1 gene responsible for the expression of CB1 receptors, and the ones without it were studied.
The study showed that the mice without the CNR1 gene lost principal neurons in their hippocampus, which are essential for learning. Other tests were performed on the mice showed effects of lack of the CNR1 gene on memory as well.
This study gives a clear picture of the impact of CB1 receptors on aging. Also in another study, research revealed that the activation of CB1 reduced oxidative stress. And as we all know, oxidative stress is caused by free radicals which are the major cause of premature aging.
CB1 and Immune Modulation
Although the CB2 is largely associated with immune functions (due to its presence in abundance in the immune system), CB1 receptors also mediate some major immune functions, especially immune modulation via the T-cells and B-cells.
Through immune modulation, CB1 may be involved in the reduction of neuroinflammation by combining some of our immune responses, while protecting our neurons.
The relativity of CB1 and immune modulation is not far-fetched. Since the discovery and continued research of the ECS, there has always been evidence to prove that CB1 receptors and ligands are found in the immune cells. A study shows that the signalling of CB1 and CB2 regulates the immune cells thereby aiding in the suppression of tumours.
CB1 and Sleep
No one wants to have their sleep disturbed but a lot of people are currently living with different kinds of sleeping disorders. CB1 receptors, when activated, can help with this. Activated CB1 receptors can sedate us. The signal for this is sent from the basal ganglia where the CB1 receptors are found in abundance.
In an experiment involving the administration of Delta9-THC, evidence suggests that the cannabinoid receptors play an active role in modulating different neurobiological functions including sleep generation.
CB1 and Food Intake
One of the major roles of CB1 in ECS is managing our appetite. CB1 receptors, especially those located in the hypothalamus, play a huge role in our appetite and metabolism. Our drive to eat for hunger and survival, and the drive to eat for pleasure and enjoyment is controlled to a large extent by the CB1.
There have been recent discoveries on the connection between microbes in our gut and the ECS. Further studies into the relationship show the promise of explaining other roles of CB1 in our metabolism.
The CB1 receptor is the most popular of the receptors in the Endocannabinoid system, it is activated by both Endocannabinoids and Phytocannabinoids. The CB1 receptor is a G protein-coupled receptor (GPRC), which allows it to react with G1 and Gs proteins in carrying out its roles in the ECS, especially the inhibition of neurotransmitters.
The CB1 receptors are encoded in the CNR1 gene which is on the 6th chromosome. The deletion of this gene through injury to the chromosome may lead to accelerated aging, especially brain aging. The cognitive abilities will be affected and neurogenerative diseases may occur.
CB1 receptors are very key to our metabolism as they stimulate our drive to eat for survival as well as our drive to eat for enjoyment.