Better pain management with CBD according to Harvard Med

Two Harvard Medical School professors combined their respective skills to find the optimal treatment for pain. Cannabinoids initially lacked a researcher’s focus, but CBD hit the right targets for better pain management. An optimal pair of pain signals was the focus of their joint research, proving the promiscuous nature of CBD.

Clifford Woolf, MB, B.Ch., Ph.D. of Boston Children’s Hospital, along with Bruce Bean, Ph.D. at Harvard Medical School to find a drug that treats pain. More specifically, her quest was for a drug that would orchestrate an iconic duet. The neurobiologists wanted a drug to produce a specific signal, and Dr. Bean already knew that CBD turns off another (sodium ions). (1)

THC versus CBD and pain

We have discussed the relationship that another signaling pair has with CB1 receptor agonists in the gut nerve (vagus nerve). THC relieves pain by regulating the cellular potassium and calcium switches that send signals up and down the nerves. Otherwise, CB1 agonists like THC inhibit acetylcholine, further bypassing sensitivity at the nerve endings.

Cannabinoids relieve pain by moderating a symphony of sensory signals. (1, 2) However, unlike THC, CBD does not act directly on CB (cannabinoid) receptors. And mechanisms targeted by CBD to treat pain have not been fully identified in research. (2) Professors Woolfe and Bean quantified the current and flux of potassium ions in mice under different conditions to assess pain responses.

Sensory maneuvering

A 2008 paper co-authored by Ken Mackie identified the function of a putative third binding site for cannabinoids. (3) THC and CBD have opposite effects on the receptor known as GPR55, which affects a specific type of potassium signal – the M-current. So CBD performs half of the duet via the third cannabinoid receptor.

A particular heat-sensing channel likely exists on the sodium side of CBD’s pain management duet. For example, ionic sodium helps carry sensation from the base of a large facial nerve to its control board in the brainstem. And CBD partially reverses this type of pain signal by desensitizing TRPV1—sodium ions are one of TRPV1’s less-discussed targets. (4-6)

Pain treatment with CBD and toxic receptors

Another example of TRPV1 desensitization is the pleasant sensation of a hot shower. However, CBD is more dynamic than hot water and spicy peppers. As such, the cannabinoid hits multiple targets in the body. Previously discovered Dr. Bean that tiny doses of CBD inhibit a toxic receptor, TTX. And sodium channels are blocked by TTX inhibition and not just TRPV1 desensitization. (1)

In mouse neurons, small doses of CBD act as a more potent pain reliever than an equal dose of bupivacaine. Of course, CBD is an imperfect drug due to its lack of selectivity. (2) In summary, CBD targets multiple sensory signals to induce analgesia.

Let us know in the comments if you or someone you know uses CBD for pain management. Would you like a follow-up study on CBD and toxic receptors in human neurons??

Sources

1. Zhang HB, Heckman L, Niday Z, et al. Cannabidiol activates neuronal Kv7 channels. elf. 2022;11:e73246. Published February 18, 2022. doi:10.7554/eLife.73246
2. Zhang HB, Bean BP. Cannabidiol inhibition of mouse primary nociceptors: tight binding to slowly inactivated states of Nav1.8 channels. J Neurosci. 2021;41(30):6371-6387. doi:10.1523/JNEUROSCI.3216-20.2021
3. Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M-current. Proc Natl Acad Sci US A. 2008;105(7):2699-2704. doi:10.1073/pnas.0711278105
4. Gambeta E, Chichorro JG, Zamponi GW. Trigeminal neuralgia: A review from pathophysiology to pharmacological treatments. mol pain. 2020;16:1744806920901890. doi:10.1177/1744806920901890
5. U. Anand, B. Jones, Y. Korchev et al. CBD effects on TRPV1 signaling pathways in cultured DRG neurons. J Pain Res. 2020;13:2269-2278. Published September 11, 2020. doi:10.2147/JPR.S258433
6. Binshtok, A., Bean, B. & Woolf, C. Inhibition of nociceptors by TRPV1-mediated entry of opaque sodium channel blockers. Nature 449, 607-610 (2007).