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The Entourage Effect

You got your feet wet with our CBD Basics article and then took your learning to the next level with our ECS article. Now it’s time to further your knowledge with one of the most challenging topics to understand – “The Entourage Effect”. The name even sounds mysterious (or maybe a little like a cable channel series.) 

Cannabis research and all things associated with it such as the ECS (see Level 2) and the therapeutic potential of CBD is in its infancy. Although “The Entourage Effect” is theorized, additional research is underway that hopes to turn theory into reality. We hope you enjoy this Level 3 topic.

Where Did This All Start?

Back in 1998, Professors Raphael Mechoulam and Shimon Ben-Shabat posited that the endocannabinoid system demonstrated an “entourage effect” in which a variety of “inactive” metabolites and closely related molecules markedly increased the activity of the primary endogenous cannabinoids, anandamide and 2-arachidonoylglycerol.1

In 1999, Mechoulam and Ben-Shabat also postulated that this helped to explain how botanical drugs were often more efficacious than their isolated components, even though the single molecule synthesis remains the dominant model for pharmaceutical development.

Ethan Russo, a neurologist and director of research and development at the International Cannabis and Cannabinoids Institute in Prague realized that Mechoulam and Ben-Shabat’s findings could lend support to his idea that THC wasn’t the only pharmacological component of cannabis. Russo proposed that there were compounds other than THC in cannabis that could account for the differences in therapeutic effects various strains. After learning about terpenoids and other compounds that could be extracted Russo suggested that the compounds might be able to enhance the effects of THC.2

“When a group of compounds from the hemp plant work together, it increases the plant’s therapeutic effect as a whole.”

What is the Entourage Effect

If you’ve read any John C. Maxwell books, you’re probably familiar with the phrase, “Teamwork makes the dream work”, right? “The Entourage Effect” theorizes that when a group of compounds from the hemp plant work together, it increases the plant’s therapeutic effect as a whole. These compounds come from combined extracts from the hemp plant that are derived from the stems, seeds, stalks, leaves, and flowers of the plant. 

When it comes to CBD, choosing a full spectrum CBD product containing all of the naturally occurring components of the plant is a great way to achieve the “entourage effect”.

What Does the Science Say?

A study by pharmacologists at the University of Sydney shows that cannabinoids in a cannabis extract interact to produce much higher concentrations of cannabidiolic acid (CBDA) in the bloodstream than when CBDA is administered alone as a single molecule. 

Associate Professor Jonathon Arnold  from the Lambert Initiative for Cannabinoid Therapeutics said their study shows cannabinoids in a cannabis extract interact to produce much higher concentrations of cannabidiolic acid (CBDA) in the bloodstream than when CBDA is administered alone as a single molecule. In fact, the cannabis extract delivered 14-times higher CBDA concentrations in the bloodstream when administered orally to mice.

“Our study has shown how this operates pharmacologically for the first time. Hemp extracts provide a natural vehicle to increase the absorption of CBDA into the bloodstream via the interaction of cannabinoids at specific transport proteins in the gut,” he said.

“The entourage hypothesis holds that cannabis constituents interact to engender greater effects but there is little scientific evidence to support such an assertion. Our study shows that different cannabinoids interact to alter plasma levels of cannabinoids themselves due to what we call a ‘pharmacokinetic entourage’ effect”.

“The Entourage Effect has yet to be formally proven, but there exists some proof that combining THC and CBD may have a therapeutic impact.”

In a randomized controlled trial of oromucosal Cannabis-based extracts in patients with intractable pain despite optimized opioid treatment, a THC-predominant extract failed to demarcate favorably from placebo, whereas a whole plant extract (nabiximols, vide infra) with both THC and cannabidiol (CBD) proved statistically significantly better than both the only salient difference being the presence of CBD in the latter.3

A recent study of several human breast cancer cell lines in culture and implanted tumors demonstrated superiority of a Cannabis extract treatment to pure THC, seemingly attributable in the former to the presence of small concentrations of cannabigerol (CBG) and tetrahydrocannabinolic acid (THCA)4

The Entourage Effect Theory

The debate about THC and “The Entourage Effect” is complicated. So far many of the studies center on CBD isolate instead of broad or full spectrum CBD. Yet, some experts believe that THC, even the smallest amount, is needed to experience CBD to its fullest, which relates to the  interaction of terpenes, organic compounds found in cannabis, and phytocannabinoids to produce an “entourage effect”. (Sea King CBD carries CBD products that include terpenes and flavonoids in their formula to encourage the entourage effect.)

“…selective breeding of cannabis chemotypes rich in ameliorative phytocannabinoid and terpenoid content offer complementary pharmacological activities that may strengthen and broaden clinical applications and improve the therapeutic index of cannabis extracts containing THC, or other base phytocannabinoids.”5

Wikipedia offers a somewhat simple definition of the entourage effect. “The entourage effect is a proposed mechanism by which cannabis compounds other than tetrahydrocannabinol (THC) act synergistically with it to modulate the overall psychoactive effects of the plant.” In other words, the combination of THC, terpenes and perhaps other compounds work together to have a modifying influence on the effectiveness of CBD. 

Of course all of this relates to the impact CBD and it’s compounds has on the endocannabinoid system, which is not a theory, but has been long proven to exist in our bodies.

Conclusions

There is a lot of information concerning “The Entourage Effect” on the Internet so there is little value in rewriting what already exists; however, Sea King CBD is keenly interested in and will remain focused on learning about any new studies that validate the existence of an “entourage effect”.  When we acquire new knowledge you can count on us updating our FAQ page or writing a blog article about it. 

The good news is you have a choice when it comes to CBD products — Isolate, Broad Spectrum, or Full Spectrum. It gets down to your needs. As always we recommend that whichever product you choose, start taking it at a low dose and increase the dose until you get the effectiveness you desire.

Peace of Mind Guarantee

Remember, when you make a purchase from Sea King CBD you are also getting our 100% Peace of Mind Guarantee. Plus, all of our CBD is tested by third party laboratories plus.

References

[1] Russo EB. “The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No “Strain,” No Gain.” Front Plant Sci. 2019;9:1969. Published 2019 Jan 9. doi:10.3389/fpls.2018.01969 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334252/

[2] Lewis MA, Russo EB, Smith KM. “Pharmacological Foundations of Cannabis Chemovars.” Planta Med. 2018 Mar;84(4):225-233. doi: 10.1055/s-0043-122240. Epub 2017 Nov 21. PMID: 29161743. https://pubmed.ncbi.nlm.nih.gov/29161743/

[3] Johnson J. R., Burnell-Nugent M., Lossignol D., Ganae-Motan E. D., Potts R., Fallon M. T. (2010). “Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain.” J. Pain Symptom Manage. 39 167–179. 10.1016/j.jpainsymman.2009.06.008 https://pubmed.ncbi.nlm.nih.gov/19896326/

[4] Sandra Blasco-Benito, Marta Seijo-Vila, Miriam Caro-Villalobos, Isabel Tundidor, Clara Andradas, Elena García-Taboada, Jeff Wade, Stewart Smith, Manuel Guzmán, Eduardo Pérez-Gómez, Mara Gordon, Cristina Sánchez.
“Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer”.
Biochemical Pharmacology, Volume 157, 2018. Pages 285-293,
ISSN 0006-2952, https://doi.org/10.1016/j.bcp.2018.06.025. https://www.sciencedirect.com/science/article/pii/S0006295218302387

[5] Apeks Supercritical. “How to extract CBD oil – The extraction process & how to make CBD oil” https://www.apekssupercritical.com/cbd-extraction-process/

[6] Russo EB. “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.” Br J Pharmacol. 2011;163(7):1344-1364. doi:10.1111/j.1476-5381.2011.01238.x https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165946/

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