Cannabinoids were originally thought to act in a nonspecific way by interacting with cell membrane-associated mechanisms. However, the discovery of the endocannabinoid system and the investigation of the CB1 receptor has lead researchers to discover the specific activity of the cannabinoid 2 receptor (CB2 receptor). Research has suggested that endocannabinoid signaling through CB2 receptors serves an overall protective role in the body.5
Introduction: Cannabinoid 2 Receptor
Unlike CB1 binding compounds like THC, CB2 receptor agonists do not produce a psychoactive “high.” Because of this, the medical community is very interested in CB2-binding compounds. Compounds that can bind with CB2 (receptor agonists) have the potential to aid in the treatment of neurological, psychiatric, cardiovascular, and liver disease and dysfunctions in particular.5
CB2 receptor agonists like CBD have demonstrated their value in reducing inflammatory pain, acute pain, post-operative pain, neuropathic pain, and cancer pain. Substantial research of CB2 receptor agonists like CBD is ongoing. This research is mainly for their use in defending against neurodegenerative diseases, immunological dysregulation, inflammation.4,6 CB2 agonists may also promote the healthy function of the heart, liver, kidneys, and bones.
CB2 Receptor: ECS Relationship
The endocannabinoid system (ECS) regulates chemical signaling of neurotransmitters in the body and has been found to play a vital role in maintaining balance (homeostasis). In recent years, research has demonstrated that the endocannabinoid system plays a significant role in regulating everyday bodily functions.
ECS Regulated Functions
- Temperature regulation
- Pleasure sensation
- Pain sensation
- Psychological reward system
In the endocannabinoid system, cannabinoid receptors CB1 and CB2 are distributed through the central and peripheral nervous systems. This distribution runs through the brain, organs, and tissue of the body. Endocannabinoids are naturally produced by the body to interact with the ECS. However, cannabinoids from the cannabis plant and synthetic versions created in laboratories are also able to bind to cannabinoid receptors.6
You can find the CB1 receptor in the central nervous system. However, CB2 is distributed mainly in the peripheral nervous system.5,6 The CB2 receptor was identified initially in the spleen, and its discovery was published in 1993. Both receptor types have similar biological pathways, where they are coupled through G proteins to adenylyl cyclase and mitogen-activated protein kinase.
CB2 receptors are mainly found in immune cells like microglia, osteoclasts, and osteoblasts.4,6 Cannabinoid 2 receptors are also located in some central and peripheral neurons, but their activity with those neurons is less understood. Activation of CB2 receptors leads to inhibition of neurotransmitters, which are chemical signals that help the cells of the body communicate with each other. CB2 receptor activation also affects immune cell secretion of inflammatory compounds called cytokines.
What Are CB2 Receptors?
CB2 receptors bind with the endocannabinoid 2-AG. They are indirectly activated but also weakly directly activated by CBD found in cannabis. The cannabis terpene β-caryophyllene also interacts with CB2 receptors, which has stimulated interest in the use of terpenes alone or in conjunction with cannabinoids to stimulate the endocannabinoid system.1,6
CB2 receptors help regulate pain sensation and immune system functions like inflammation and appetite. The activation of the cannabinoid 2 receptor through CBD results in powerful anti-inflammatory action that is thought to be even stronger than aspirin.
Potential for Relief
Since inflammation plays a vital role in the pathologies of many diseases and conditions, CB2 agonists have fantastic potential as a natural source of symptom relief. High concentrations of CB2 receptors have been found throughout the gastrointestinal (GI) system. Compounds like CBD could help regulate and relieve symptoms of Crohn’s disease, colitis, and inflammatory bowel syndrome (IBS).6
Using CBD for joint pain and arthritis may also strongly benefit from the anti-inflammatory activity of cannabinoid 2 receptor agonists. Skin conditions like acne and rashes are thought to benefit from CBD and other CB2 agonists. CB2 agonists are also studied for their ability to affect the brain’s “reward system.”3 There is growing evidence that CB2 can help in addiction therapy for substances like opioids, recreational drugs, and nicotine.
Importance of CB2 Receptors
CB2 receptors help realize primary CBD benefits. These extensive benefits range from reducing symptoms of anxiety, reducing pain and inflammation, and promoting CBD brain effects and nerve health. The CB2 receptor’s abilities to prevent and relieve symptoms of some cancers are suspected.2 Severe conditions like Multiple Sclerosis, Alzheimer’s Disease, Post Traumatic Stress Disorder, epilepsy, and diabetes have shown evidence of improvement through the use of CBD products.
Final Thoughts: CB2 Receptors
CB2 receptors are drawing more and more attention as a target for improving overall health. Scientists everywhere are exploring new ways to relieve symptoms of several diseases and health conditions using the CB2 receptors. The cannabinoid 2 receptor is widespread through the body and lacks the psychoactive effects of THC (see our comparison article of THC vs. CBD). CBD is growing a reputation for providing the natural benefits of cannabis without the high.
CB2 binding compounds like CBD and the cannabis terpene β-caryophyllene have become particularly popular in research for their therapeutic potential. Many people are already experiencing the benefits of CBD products, which may be more effective than THC products, especially for inflammation reduction.
- Dhopeshwarkar, A., & Mackie, K. (2014). CB2 cannabinoid receptors as a therapeutic target-what does the future hold?. Molecular pharmacology, 86(4), 430–437. doi:10.1124/mol.114.094649 Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164977/
- Grotenhermen, F., & Müller-Vahl, K. (2012). The therapeutic potential of cannabis and cannabinoids. Deutsches Arzteblatt international, 109(29-30), 495-501.
- Katona, I., & Freund, T. F. (2012). Multiple functions of endocannabinoid signaling in the brain. Annual review of neuroscience, 35, 529-558. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273654/?report=classic
- Kaur, R., R Ambwani, S., & Singh, S. (2016). Endocannabinoid system: a multi-facet therapeutic target. Current clinical pharmacology, 11(2), 110-117. Retrieved from: https://www.researchgate.net/profile/Sneha_Ambwani/publication/301533431_Endocannabinoid_System_A_Multi-Facet_Therapeutic_Target/links/5a544667a6fdccf3e2e29f74/Endocannabinoid-System-A-Multi-Facet-Therapeutic-Target.pdf
- Mechoulam, R., & Parker, L. A. (2013). The endocannabinoid system and the brain. Annual review of psychology, 64, 21-47. Retrieved from: https://www.researchgate.net/profile/Raphael_Mechoulam2/publication/229163258_The_Endocannabinoid_System_and_the_Brain/links/5469dae80cf2f5eb18054fc8/The-Endocannabinoid-System-and-the-Brain.pdf
- Turcotte, C., Blanchet, M. R., Laviolette, M., & Flamand, N. (2016). The CB2receptor and its role as a regulator of inflammation. Cellular and molecular life sciences : CMLS, 73(23), 4449–4470. doi:10.1007/s00018-016-2300-4 Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075023/