CB2 and Pain: The Elusive 2nd Cannabinoid Receptor

A research team composed of members from China, Russia, and the US have announced a significant advance in understanding the structure of CB2, one of 2 cannabinoid receptors in the human endocannabinoid system. Cannabinoid receptors can be targeted to address a range of pathological conditions, including chronic pain. CB1 receptors are mostly located in the nervous system, while CB2 receptors are mostly in the immune system, and are seen as potential targets for treating inflammatory neuropathic pain, among other conditions. But since the amino acid sequences that encode the 2 receptors are 44% the same, creating a drug that selectively targets CB2 requires a precise knowledge of its structure, that has heretofore been elusive.

The researchers created a crystal from CB2 receptors bound to antagonists, or molecules blocking the receptor. X-ray analysis permitted the determination of both the CB2 structure and the way in which it connects to the antagonist. A further advance in the current work involved the use of predictive software to identify mutations that could be introduced to stabilize the naturally unstable receptor and enabling their study. Coauthor Petr Popov, PhD, assistant professor at the Skolkovo Institute of Science and Technology, Moscow, commented, “Now that the structures of both cannabinoid receptors are known, we can design selective compounds targeting only one of the receptors, as well as agents with a desired polypharmacological profile targeting both receptors at once.” The work was published in January in the journal Cell.

Read about the findings.

The journal abstract may be read here.

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• medical cannabinoids