The Entourage Effect: Part 2

The Entourage Effect: Part 2

So how can a plant like cannabis potentially play such a diverse treatment role across a variety of health conditions?

The answer may lie in the pharmacological phenomenon dubbed the “entourage effect”, a mechanism that is unique to whole-plant cannabis medicine and one that paints a much more illustrious and detailed picture of the inner workings of cannabis on the human body and mind.

Essentially, consuming whole-plant cannabis unlocks a much more diverse symphony of cannabinoids (active chemical compounds in cannabis) and terpenes (aforementioned aromatic hydrocarbons that give cannabis its unique smell) that also bind to receptors in the brain, consequently complementing and synergizing with the cannabinoid profile of that plant to provide more nuanced physiological and psychoactive effects (Russo, 2011). This pharmacological synergy among “~140 distinct cannabinoids and ~400 terpenes, the relative levels of which largely determine their therapeutic effect” is called the “entourage effect” and is exactly what makes cannabis such a unique medicinal product (Fanelli et al., 2017). This sort of harmonious synergy among the hundreds of active constituents in the cannabis plant obviously cannot be emulated in pharmaceutical drugs, which rely on a “single molecule” mechanism.

While whole plant medicine like cannabis is considered “living medicine”, the downside here is that our extremely rigorous system for testing and approving drugs makes testing something like cannabis extremely difficult if not impossible under the current structure. For those who have seen “The Price is Right”, a pharmaceutical drug can be represented by dropping one single ball (the drug) in the game Plinko and observing how it hits each one of the pegs and (hopefully) falls into the right hole (receptor in the brain/body). In the context of cannabis, this would be like dropping a hundred different colored balls and trying to study them all at once.

It becomes almost impossible to control for confounding factors and identify which combination and permutation of cannabinoids/terpenes causes what effects. However, this lack of proper testing protocols and mechanisms to be able to adequately experiment and approve whole plant cannabis as a medical treatment should push us further to develop better testing methods instead of throwing the baby out with the bathwater and disregarding cannabis treatment entirely. There is much to be learned still about the mysterious effects of cannabis on the human body and, as with most things science, the more we find out the more questions and complexities we unravel.

It’s said that the most sophisticated pharmacy in the world is in our brains. Indeed, our brain produces a variety of neurotransmitters from endorphins to dopamine to cannabinoids, all of which can be also be exogenously affected and modulated by drugs such as opiates, stimulants and cannabis respectively. To better understand our own, intrinsic cannabinoid receptor system, we need to further research the novel and specific pharmacological effects exogenous phytocannabinoids and terpenoids have on the human body. A 2006 study by Massa & Monory discuss the protective role the endocannabinoid system has on the GI tract and how medicinal preparations of cannabis have been used to treat GI disorders “in past centuries” (2006). Indeed, cannabis has been successfully shown to be efficacious in the treatment of inflammatory bowel disease (IBD), even showing successful remission in a small sample of Crohn’s patients (Naftali et al., 2013)(Ahmed & Katz, 2016).

The radically dramatic therapeutic effects observed in epilepsy patients, especially pediatric ones, who use cannabis to treat their seizures is stark and cannot be ignored. Rosenberg, in his 2015 study, discussed cannabinoid treatment for epilepsy and the novel role of CBD in preventing seizures, however, using whole plant cannabis in this case “both contribute to and reduce seizures” (2015). This further demonstrates the unique and elusive pharmacology of Cannabis Sativa and it’s relationship with our own endocannabinoid system. Thus, this also demonstrates the dire need to conduct more studies and trials using cannabis to gain a better understanding of not only cannabis but a better understanding of us.

As the cannabis industry continues to evolve, the wide range of products being manufactured/grown/crafted will continue to expand and experiment with different levels of cannabinoids and terpenes. Creating extracts and concentrates allows one to customize THC:CBD ratios that are difficult or perhaps even impossible to find in nature.  Thus, it is the prevalence and concentration of cannabinoids and terpenes in the trichromes of the Cannabis Sativa plant that, when consumed, work synergistically to provide the unique and diverse experiences that is whole plant medical cannabis. While it may be difficult to truly grasp the biological and pharmacological mechanisms behind the “entourage effect”, it is now clear that there is a more intertwined and complex relationship between the hundreds of active constituents in the cannabis plant and their individual effects on human physiology. Factoring in the diverse biology of each individual patient begins to indicate just how many orders of magnitude there are in the many levels of harmonious pharmacological synergy between the symphony of cannabinoids and terpenoids, all coming together to create an experience that is truly unique and special unto itself.

This author supports the descheduling of C. Sativa and increased, more affordable access to medical cannabis across the country.

References

Ahmed, W., & Katz, S. (2016). Therapeutic use of cannabis in inflammatory bowel disease. Gastroenterology & Hepatology, 12(11), 668-679.

Massa, F., & Monory, K. (2006). Endocannabinoids and the gastrointestinal tract. Journal of Endocrinological Investigation, 29(3 Suppl), 47-57.

Mechoulam, R., & Parker, L. A. (2013). The endocannabinoid system and the brain. Annual Review of Psychology, 64, 21-47. doi:10.1146/annurev-psych-113011-143739 [doi]

Naftali, T., Bar-Lev Schleider, L., Dotan, I., Lansky, E. P., Sklerovsky Benjaminov, F., & Konikoff, F. M. (2013). Cannabis induces a clinical response in patients with crohn’s disease: A prospective placebo-controlled study. Clinical Gastroenterology and Hepatology : The Official Clinical Practice Journal of the American Gastroenterological Association, 11(10), 1276-1280.e1. doi:10.1016/j.cgh.2013.04.034 [doi]

Rosenberg, E. C., Tsien, R. W., Whalley, B. J., & Devinsky, O. (2015). Cannabinoids and epilepsy. Neurotherapeutics : The Journal of the American Society for Experimental NeuroTherapeutics, 12(4), 747-768. doi:10.1007/s13311-015-0375-5 [doi]

Russo, E. B. (2011). Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology, 163(7), 1344-1364. doi:10.1111/j.1476-5381.2011.01238.x [doi]

Welty, T. E., Luebke, A., & Gidal, B. E. (2014). Cannabidiol: Promise and pitfalls. Epilepsy Currents, 14(5), 250-252. doi:10.5698/1535-7597-14.5.250 [doi]

 

By Gaurav Dubey

 

 

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