How CBD Interacts with CB1 & CB2 Receptors

Cannabidiol (CBD) interacts with two dominant receptors (CB₁ and CB­₂) of the endocannabinoid system (ECS). How it does so has been widely debated in the literature. The truth about CBD’s interaction with CB­₁ & CB­₂ is broken down in this article.

Generally, it is understood that CBD produces its effects through diverse molecular pathways. As it is, about 65 different pathways have been identified.[1] When it comes to endocannabinoid receptors, CBD has a definite action on each of them. Through this action, some of CBD’s therapeutic effects are appreciated.

CB₁ Receptors

These receptors are predominantly found in the central nervous system.[2] CBD acts as an allosteric modulator of CB₁ receptors.[3] An allosteric modulator changes the way the receptor works without actually activating it. This means that CBD can cause inhibitory effects on CB₁ agonists (substances that increase the receptor’s activity), such as tetrahydrocannabinol (THC).

Since CBD does not occupy the same position as THC on the receptor, it cannot displace THC. However, it can “negate” some of its effects.[4] These include improving memory loss associated with THC use and counteracting THC’s psychoactive effects .

CB₂ Receptors

Early on, it was believed that CBD binds directly to CB₂ receptors. Crazy enough, it was also thought that there were no CB₂ receptors in the central nervous system (the brain and spinal cord).[5] What we now know is that these are myths.

While it’s true that there are CB₂ receptors in the brain, most are found in the immune system.[2] CBD acts as an inverse agonist at the CB₂ receptor, meaning that it occupies the same position on the receptor and produces the opposite effect of the agonist. And–to make things a bit more complicated–its effects vary widely depending on its concentration.[6]

In summary, CBD acts on cannabinoid receptors very differently. And, unlike THC, CBD also acts through many different non-cannabinoid receptor pathways to produce some of its therapeutic effects, explaining how it can be beneficial for so many different conditions. It’s also important to remember that CBD and THC are not the only cannabinoids in the plant and we are still learning how other compounds interact with this system, as well as terpenes.

As research continues to reveal complex interactions within in the ECS and beyond, stayed tuned as we keep on the beat of the evolving literature.

Image Source: https://www.cbddelivered.com/blog/cannabinoid-receptors-why-care-about/

References

1. Ibeas Bih C, et al. Molecular targets of cannabidiol in neurological Neurotherapeutics. 2015;12(4):699-730.
2. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153(2):199-215.
3. Laprairie RB, et al. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. British J Pharmacol. 2015;172(20):4790-4805.
4. Hudson R, et al. Cannabidiol counteracts the psychotropic side-effects of Δ-9-tetrahydrocannabinol in the ventral hippocampus through bi-directional control of ERK1-2 phosphorylation.” J Neurosci. 2019;39(44):8762-8777.
5. Onaivi ES. Commentary: Functional neuronal CB2 cannabinoid receptors in the CNS. Curr Neuropharmacol. 2011;9(1):205-208.
6. Pellati F, et al. Cannabis sativa L. and nonpsychoactive cannabinoids: Their chemistry and role against oxidative stress, inflammation, and cancer. Biomed Res Int. 2018:1691428.