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What is the entourage effect?

03/12/2020 6 MIN. READ Mirko Berger
03/12/2020 6 MIN. READ Mirko Berger

Cannabis is an incredible plant with an astonishing number of applications. Industrial hemp can be used as a raw material in an unbelievable number of end products, like textiles, building materials, biodegradable plastic alternatives and even automobiles. But in addition to all of these practical uses, cannabis also has a completely different aspect, namely as a medicinal plant. Nearly 600 different chemical compounds have been detected in the cannabis plant so far, and that includes over 120 cannabinoids, hundreds of different terpenes, flavonoids, polyphenols, lignans and numerous trace elements.

The theory behind the entourage effect is that the naturally occurring compounds and substances in the plant (in particular the cannabinoids and terpenes) work together in synergy to reinforce one another or influence one another in different ways. It’s why when it comes to the entourage effect, you’ll often hear the age-old saying: "The whole is greater than the sum of its parts."

At this point, it’s important to note that the entourage effect is currently a still-controversial theory. While many cannabis researchers are firmly convinced of its existence, there are others who say that there’s no evidence to support it, and the term itself is typically used only by the cannabis industry for marketing purposes.

What is the entourage effect?

In 1964, we learned that certain cannabinoids are responsible for specific effects when Israeli scientists Raphael Mechoulam and Yechiel Gaoni isolated the first known cannabinoid tetrahydrocannabinol (better known as THC). Thanks to their “discovery,” cannabis researchers finally had a better understanding of what constitutes the well-known “high” feeling that often comes from consuming the plant. However, after many years of further research, Mechoulam and his colleagues came to the conclusion that THC was probably responsible for only parts of that “high.” They suspected that other compounds in the plant played a role in determining the sensation and called this phenomenon an “entourage effect.”

For example, studies in 2006 showed that the occasional yet extremely unpleasant negative side effects of THC could be significantly reduced by CBD. This led to theories that CBD could slow down the breakdown of THC in the body and thereby alleviate negative effects like anxiety, while at the same time increase the positive effects of THC. The author of this study, Ethan Russo, has become one of the main proponents of the entourage effect; he takes the position that we need to look at the cannabis plant in its entirety to understand all of its potential effects.

The entourage effect is also responsible for why some believe that full- and broad-spectrum CBD extracts work better than CBD isolates, since many other compounds from the hemp plant are still present in these types of extracts. A study that was published in early 2020 supports this assessment as well. These researchers found that whereas pure CBD isolate reached its maximum effect at a certain dose, the plant-derived extract also had a stronger effect as the dose increased, finding it more efficacious for the treatment of inflammatory conditions. However, this study was carried out on mice and so far there have been no comparable tests on humans.

That said, the concept of plant synergy did not just come about because of cannabis. In herbal medicine, great importance is attached to synergy, and preparations often combine several herbal components whose effects are intended to support and enhance each other. Yet here, too, the evidence is extremely thin. In 2009, the German medical journal Deutsches Ärzteblatt explained: “According to the testing rules in place today, a separate controlled study would be required for each ingredient in the extract and in the total mixture, which is hardly economically justifiable. The therapeutic synergy of the ingredients of total plant extracts can neither be proven nor disproven."

The cannabis plant and its ingredients

Cannabis is much more than just THC and CBD. The plant also produces more than 100 other cannabinoids like CBN, CBC, CBG and dozens more — as well as hundreds of terpenes, flavonoids, amino acids, proteins, sugars and micronutrients. According to the theory of the entourage effect, all of these components work together in synergy and thus achieve the resulting effects generated by the respective plant.  


What are terpenes?

Terpenes are aromatic compounds in cannabis that can also be found in the essential oils of lavender, orange, black pepper, eucalyptus, and in many other plants. They give cannabis its unmistakable smell. Depending on the plant’s terpene profile, which can vary greatly from variety to variety, they give off a different scent and flavor. Advocates of the entourage effect also speculate that terpenes are also responsible for or at least contribute to how different cannabis plants yield different effects.

More than 40,000 naturally occurring terpenes and terpenoids have been identified thus far, over 200 of which are found in the cannabis plant.

The most common terpenes

Myrcene
Myrcene is the most common terpene found in the cannabis plant and accounts for up to 50% of the total terpene content in some cultivars. It is a monoterpene, which means that it has a relatively simple structure. Like many other terpenes, myrcene is a component found in numerous everyday products, occurring naturally in, for example, fresh mangos, hops, basil and thyme. It has a pleasant, earthy and clove-like scent and tastes slightly sweet and citrusy, and has therefore become a popular aroma in many food and household products.

Myrcene is said to have relaxing, anti-inflammatory and analgesic effects.

Limonene
Like myrcene, limonene is a monoterpene with a sweet citrus flavor and a strong lemon aroma, which is why it’s used in a wide variety of products, such as detergents and cosmetics. It’s also one of the most commonly terpenes found in nature, best-known for appearing in citrus peels, but it is also found in many other plant species, including cannabis.

Research, albeit mostly from animal studies, has shown limonene to have a large number of potentially beneficial properties. Like many other terpenes, limonene is “considered to be a potential anti-inflammatory candidate,” as demonstrated in this 2010 study. According to the American National Cancer Institute, limonene could be responsible for “potential chemopreventive and antitumor activities.” Although the exact mechanism is unclear, limonene appears to induce cell death, also known as apoptosis. A 2017 study suggests that limonene's anti-inflammatory effects could help fight ulcerative colitis in rats. It’s currently unclear whether or not these takeaways can be applied to humans. Another study from 2013 also found that inhaled limonene has anti-anxiety properties, but again, these data come from animal experiments as well.

Alpha-pinene
Alpha-pinene (also known as α-pinene) has a pleasant pine scent and is found in large quantities in the resin of conifer trees. Other sources of alpha pinene include rosemary, eucalyptus oil and orange peel oil. Because of its fresh aroma, alpha pinene is often used in detergents, air fresheners, and perfumes.

According to this study from 2014, alpha pinene appears to be effective at reducing inflammation. It’s also believed that it plays a crucial role in the Japanese nature therapy called shinrin-yoku (“forest bathing") in which forest trees, particularly coniferous forests, are sought out so that practitioners can take in or "bathe" in their aromatic air — a trend that’s gaining more and more traction in Germany.

Linalool
Linalool is found in more than 200 plant species, in addition to cannabis, and has a variety of uses. Thanks to its floral scent, it’s a common ingredient of many hygiene products. If you have soaps or shampoos at home (assuming you do...), some are likely to contain linalool.

Linalool also appears to have anti-inflammatory properties. A 2013 study examined the anti-inflammatory effects of linalool and found that it inhibited inflammatory processes, both in vitro and in the body (in this case in mice). The study concluded that it might be worth taking a closer look at linalool as a possible candidate for the treatment of inflammatory diseases.

The importance of the entourage effect for CBD products

With terpenes exhibiting such great potential, it’s easy to understand why they (at least theoretically) could also bolster the positive properties of CBD. Proponents of the entourage effect argue this exact point. With several hundred ingredients in the hemp plant, many of which containing their own health-boosting properties, it stands to reason that the interaction of all these compounds is far greater than either of the substances alone. 

That’s why full- or broad-spectrum CBD products are typically viewed as “more complete” than pure isolates by most in the cannabis industry. Then again, a recently published study was determined that terpenes were unlikely to have an entourage effect... 

As you can see, we’re still far from getting a final word on the topic. And as with so many topics related to cannabis, the same applies here: More research is needed!

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