What do chili peppers, hemp and runners high all have in common?

For all of you jumping up and down screaming, “TRPV1 Receptor Sites!” take a bow, claim your molecular biology nerd prize, and hush up. For the rest here is a quick introduction:

TRPV1 are just one of many TRPV receptor sites located throughout the central and peripheral nervous systems. The V part of their name stands for the vanilloid family of compounds that have an affinity for these sites, and TRP (“trip”) are a group of receptors throughout cell membranes where they play a role in ion flow from one side of a cell membrane to the other, or more specifically in TRPV1’s case, the transmission and modulation of pain.1

It is this special characteristic of TRPV1 sites that we will focus on.

So why hot peppers?

Well, to get there, let’s introduce another bit of trivia first. The TRPV family of receptors have another common name, the Capsaicin Receptors. If capsaicin sounds familiar to you, it is because it is the compound responsible for the spicy sensation we experience when we eat chili peppers. So why capsaicin? Well this is because capsaicin is actually a member of the vanilloid family. While it is true that capsaicin can burn if rubbed into your eyes or other mucus membranes it is this ability that capsaicin has to stimulate the nervous system that we can rely upon to create neurological fatigue in the TRPV1 sites. It is this fatigue through repeated exposure that ultimately leads to a general desensitization of the receptor site which results in pain relief.1,2

The Bliss Molecule

Runner’s high is usually described as elation upon completion or during exercise coupled with reduction in anxiety and a sense of calm. The endocannabinoid – those cannabinoids which are created inside your body and have an affinity to the same receptor sites as THC – largely believed responsible for this sensation is named anandamide (AEA), hence its nickname the Bliss Molecule.3 Unrelated research done on TRPV1 receptors has shown that AEA also acts as an agonist and has an affinity for TRPV1 sites.4

What’s the pay off? Well if you recall these are the receptor sites which are responsible for pain signaling and modulation. As we saw before over stimulation of these receptors can lead to pain management. The key difference is that anandamide stimulates these receptors in a manner different from capsaicin.

But wait, you mentioned HEMP before?

Absolutely and here is the pay off for all of it.

Hemp also has an affinity to the same TRPV1 receptors that capsaicin and AEA do which result in further methods of stimulation.5, Hemp also produces anti-inflammatory responses inside the body and plays a role in pain management via non-TRPV1 routes.6,8 Hemp enhances the effects of AEA as it remains in your system longer due to hemps interaction on the sites which help process AEA from your bloodstream.6,7 AEA around longer in your system to stimulate TRPV1 sites longer? Yes, please.

It is this synergy of hemp, AEA, and capsaicin and their interaction with TRPV1 sites that are of particular interest here and require more advanced study.

The next blog post in this series will be about the endocannabinoid system in general.

1 – Wong, G. Y. & Gavva, N. R. (2009). Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: Recent advances and setbacks. Brain Research Reviews, 60(1), 267–277. https://doi.org/10.1016/j.brainresrev.2008.12.006
2 – Fattori, V., Hohmann, M., et al (2016). Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses. Molecules. 2016 Jul; 21(7): 844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273101/
3 – Fuss, J., Steinle, J., et al (2015). A runner’s high depends on cannabinoid receptors in mice. PNAS October 20, 2015 112 (42) 13105-13108; first published October 5, 2015; https://doi.org/10.1073/pnas.1514996112
4 – Muller, C., Lynch, D. L., et al. A Closer Look at Anandamide Interaction With TRPV1 Front. Mol. Biosci., 21 July 2020 https://www.frontiersin.org/articles/10.3389/fmolb.2020.00144/full
5 – Bisogno, T., Hanuš, L., et al (2001). Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. British Journal of Pharmacology (2001) 134, 845–852; doi:10.1038/sj.bjp.0704327
6 – Russo, E. (2008). Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008 Feb; 4(1): 245–259 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660/
7 – Leweke, F. M., Piomelli, D., et al (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia Transl Psychiatry. 2012 Mar; 2(3): e94.
Published online 2012 Mar 20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/
8 – Argueta, D. Ventura, C. M., et al., (2020). A Balanced Approach for Cannabidiol Use in Chronic Pain. Front Pharmacol 1010; 11:561. Published Online 2020 Apr 30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204604/

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