How inflammation and pain affect the endocannabinoid system

Cannabis, and the endocannabinoid system found in all vertebrae, act through countless mechanisms. And typically topping lists of cannabinoid effects is anti-inflammation. Less known is a vicious cycle that occurs when inflammation and pain negatively affect the endocannabinoid system, or how to stop its degradation.

Dear doctor: Ibuprofen affects endocannabinoid metabolism

Anti-inflammatory drugs are a huge market projected to be worth USD 191.42 billion by 2027. But the drugs have vast differences and nuances. For starters, ibuprofen is a common anti-inflammatory recommended almost unanimously by medical doctors. What classic doctors fail to understand is how ibuprofen partially affects inflammation and pain by protecting the endocannabinoid system. Their failure is because medical academia only recently began to recognize endocannabinology — the study of the endocannabinoid system (ECS). (1)

The ECS is an intricate, major regulatory mechanism in the body. The system is comprised of several molecules, receptors, and chemo-responsive channels. And while inflammation and pain from specific sources can degrade endocannabinoids. (2) The ECS compensates in the sense that inflammatory signals increase cannabinoid receptor expression. (3)

Is inflammation useless?

Many different things in the body cause, inhibit, or regulate inflammation, and a few mechanisms affect the endocannabinoid system.

Our bodies use inflammation as a form of emergency protection. Broken bones require some inflammation to heal properly, for example. Degradation of the endocannabinoid system plays a role here where the body releases a substance (COX-2) in response to pain. COX-2 then breaks down endocannabinoids into different inflammatory compounds.

This means that inflammation has a purpose. It’s rather the uncontrollable proliferation of inflammatory compounds that can eventually assault and damage the organism they protect. As it turns out, though, increased levels of cannabinoid receptors in response to inflammation might naturally counter endocannabinoid degradation.

Therapy for inflammation requires a precise target

Natural design is imperfect. Thankfully, we can reach beyond the human body to exogenous substances that help tune our biological systems. But cannabinoids and terpenes are but one tool. Omega-3 fats, chocolate, maca root, and black peppercorns, for example, can be beneficial as well. (4) Although a few studies now suggest the best therapy for various ECS-related diseases is to block enzymes that degrade compounds within the system.

Let us know in the comments if you have any stories to share about inflammation or pain. And don’t forget to check out this story on endocannabinoid breakdown after a Traumatic Brain Injury.

Sources

1. Karlsson, J., & Fowler, C. J. (2014). Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen. PloS one, 9(7), e103589.
2. D.; Gao, F.; Chen, C. Endocannabinoid Metabolism and Traumatic Brain Injury. Cells 2021, 10
3. Morris, G., Sominsky, L., Walder, K.R. et al. Inflammation and Nitro-oxidative Stress as Drivers of Endocannabinoid System Aberrations in Mood Disorders and Schizophrenia. Mol Neurobiol (2022). https://doi.org/10.1007/s12035-022-02800-
4. Russo E. B. (2016). Beyond Cannabis: Plants and the Endocannabinoid System. Trends in pharmacological sciences, 37(7), 594–605. 4b. Russo, E. B., & Marcu, J. (2017). Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads. Advances in pharmacology (San Diego, Calif.), 80, 67–134.
5. Poddighe, L., Carta, G., Serra, M. P., Melis, T., Boi, M., Lisai, S., Murru, E., Muredda, L., Collu, M., Banni, S., & Quartu, M. (2018). Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion. Lipids in health and disease, 17(1), 23. https://doi.org/10.1186/s12944-018-0661-4