Entourage Effect 2.0: The Entourage Effect is Real, but Full-Spectrum Cannabis is Not the Answer

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In this guest op-ed, ebbu’s CEO discusses how cannabis science finds success between the extremes.

One of the hot phrases in the cannabis industry right now is the “entourage effect.” Simply put, the thesis is that combining cannabis compounds creates a different physical or psychological impact than a single compound on its own.

While some still question the efficacy of the entourage effect, let me put to bed the question of whether it is real. It is, and I work with a team of scientists who have thousands of data points to back that up.

Before we go further, a little background:

Plants in the Cannabis Sativa L. species, which includes both marijuana and hemp, contain hundreds of different chemical compounds, including cannabinoids and terpenoids, which all interact with the mind and body to various degrees.

While two cannabinoids—psychoactive tetrahydrocannabinol (THC) and non-intoxicating cannabidiol (CBD)—have received the most attention among researchers and consumers, more than 100 other cannabinoids have been identified so far. Terpenoids/terpenes, are found in many other plants including spices, herbs, trees and fruits, and are what give cannabis strains their distinctive smells and flavors.

Each cannabinoid and terpene has a specific biochemical effect on the body. The phrase “entourage effect” was first used in the cannabis context in 1998 by a group of scientists that included “the father of cannabis research,” renowned Israeli biochemist Dr. Raphael Mechoulam. More recently, the phrase has been popularized in Dr. Ethan Russo’s 2011 paper Taming THC: Potential Cannabis Synergy and Phytocannabinoid-Terpenoid Entourage Effects, where he investigated the interactions between cannabinoids and terpenes, looking for synergies to treat pain, inflammation, depression, anxiety, addiction, epilepsy, cancer and bacterial infections.

Russo had reported previously in 2008 that: “Good evidence shows that secondary compounds in cannabis may enhance the beneficial effects of THC” as well as reduce THC’s unwelcome side effects.

From that, many people have concluded that all of the synergistic effects are beneficial. And from this, they conclude that “full spectrum” oil (the collection of all of the cannabinoids and terpenes from one or more plants) makes for the best cannabis products or cannabis-based medicine.

So, is full-spectrum oil is always the best solution for cannabis medicine and consumer products? The quick answer is no. Tailored cannabinoid formulations are far more effective and consistent, and will make up a large portion of mainstream adult cannabis consumption in the future.

Over the last three years in our cellular pharmacology lab, we have studied the effects of individual cannabinoids and terpenes on receptor cells, and then measured the activity in those cells when in the presence of a formulation that combines two or more cannabis compounds. Like Mechoulam and Russo, we have found that different combinations result in quantitatively different reactions from the cells. One compound magnifies the effect of another; another compound mitigates the effect of another.

In full-spectrum consumption, different cannabinoids act on several different receptors in the human body at the same time. I call this “chemical chaos.” You are consuming some compounds that are helpful for a condition or achieving a certain state of being, but many of the effects experienced from the whole-plant entourage effect are neither desirable nor necessary.

Worse, other cannabinoids can invoke the complete opposite of the desired result. You can try a strain that is “high CBD” or “high THC,” but products infused with whole plants will always be delivered inconsistently because each plant, even from the same strain, has a slightly different combination of compounds. A report in Nature earlier in 2018 found that the cannabinoid content of legal cannabis in Washington state varies systematically across consumer products and even across testing facilities.

Whole-plant consumption effectively throws an unknown and unquantified combination of cannabinoids at every receptor and hopes for the best. It is the ultimate in polypharmacology. The other side of the coin is using a single cannabinoid to target a single receptor like CB-1 (cannabinoid receptor 1) to perform a single activity. This is the approach taken by Big Pharma thus far, ignoring the entourage effect altogether.

Neither extreme is ideal. But between these two poles lies the best way to truly take advantage of the entourage effect: conducting scientific research to determine the best combinations of purified cannabinoids and terpenes to yield known, reliable, consistent effects.

Every day, cannabinoid scientists are identifying the unique effects of each cannabinoid and terpenoid, and the interactions between them. In our lab we have shown that formulations produce consistent, reproducible physiological and psychological effects in humans. For patients and consumers, this means a repeatable, predictable, consistent reaction or experience.

If you are trying to create a wellness product, full-spectrum is likely not the answer, as it creates an inconsistent, wildly variable reaction that we can’t control. Using scientifically proven combinations is safer and more effective than pouring all of the compounds into your body at once, and that is the true value of the entourage effect.

As the body of scientific research grows, a more thorough understanding of the exact synergistic interplay among discrete cannabinoids and terpenes will lead to sophisticated harnessing of the entourage effect. This knowledge will drive the future of cannabis products, developed for specific patient and adult consumer needs and desires.

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