What is an Entourage effect?

If you’ve been around the cannabis world for a while, you’ve probably heard of the entourage effect. This is the interconnection of individual cannabis ingredients that support each other through their mutual bond and multiply their effect.

This effect is all the better because all the molecules work relatively quickly than if those parts were working independently.

The findings on this effect were published in 1998 in a paper by Professors Raphael Mechoulam and Shimon Ben-Shabat. In their work, they described that the endocannabinoid system responds better to extracts that contain all the necessary molecules than to extracts that contain only single components (THC and CBD). The entourage effect also makes whole plant-based medicines better than those that contain only one isolated molecule.

Thus, in general, the entourage effect has been experienced and is mentioned regularly. But what does it entail and should we understand it today through further research? A lot of studies have been devoted to this effect in 2019, with scientists figuring out which molecules process this effect, but it is not yet clear. One study also looked at the fact that the entourage effect is quite overrated.

What do we know so far about the entourage effect?

For starters, we know that each cannabinoid enhances the effects of the other (THC enhances the therapeutic effects of CBD).

In a study on breast cancer tissue in vitro and in experimental animals, the presence of minor cannabinoids improved the outcome. “The cannabis extract was much more effective than the THC isolate in terms of killing and reducing tumor growth,” said Dr. Ethan Russo, MD, a pioneer in entourage effect research and founder/director of CReDO Science. “The synergistic effect of hemp extract can be explained by the presence of significant amounts of cannabigerol (CBG) and tetrahydrocannabinolic acid (THCA) in the extract compared to THC alone.”

However, according to Dr. Jordan Tishler, a medical cannabis expert and instructor of medicine at Harvard Medical School, the elements of the additive effect are proven but over-generalised. “For example, there is incontrovertible evidence that CBD … modulates the effects of THC at the site of the main receptor. Therefore, the entourage effect is real,” he said.

“The entourage effect also explains why pure THC is not particularly effective and the whole cannabis plant is better,” he said. However, he argues that the effects of the entourage effect have been extrapolated beyond the current evidence. “The ideas that other chemicals are important for CBD to work are not currently supported by anything.”

Tishler also articulates that the role of minor cannabinoids such as CBG or CBN is not yet fully understood in relation to THC or other cannabinoids. “In other words, many molecules may play a role supporting the action of THC, but that doesn’t mean they have a role supporting other cannabinoids,” he said.

What role do terpenes play here?

Terpenes play an important role in the entourage effect. However, the research to substantiate this has been rather sparse. For example, in some studies it is given that terpenes are not related to the entourage effect at all. According to the research, none of the five common terpenes in any way support the initiation of the entourage effect.

But as it happens with cannabis research, it’s never the final version.

In a 2020 study, research showed that three known terpenes (Humulene, Pinen and Geraniol) activated the CB1 receptor. The latter is responsible for physical responses such as suppression of pain perception. These terpenes kicked CB receptor function in the mice tested, confirming their therapeutic use.

According to Tishler, there is insufficient evidence that terpenes contribute to the synergistic effect of whole cannabis. However, this does not mean that we dismiss these aromatic compounds as ineffective. “There are two exceptions,” Tishler said. “Myrcene, which causes drowsiness but does so on its own, not as part of an accompanying effect, and β-caryophyllene, which may be important in pain management.”

So is the entourage effect real at the moment or not?

Tishler says the entourage effect is a real phenomenon that is poorly understood. “Currently, our understanding of entourage effect interactions is quite limited,” he said. There is not enough data to make specific products or recommendations based on other cannabinoids or terpenes. That’s not to say there isn’t whole-plant alchemy, but we haven’t yet consolidated our understanding of the mechanisms of action.

“On a clinical level, products that contain pure THC and CBD seem to be less effective than whole cannabis, suggesting that other chemicals are indeed involved – it’s just not yet clear which ones and how they work,” Tishler said.

Despite conflicting findings appearing in some publications, Ethan Russo remains a firm believer in the entourage effect. “Despite occasional failures to demonstrate the benefits of the entourage effect, which could be attributed to drugs that are not therapeutically optimized, the concept of the entourage effect is well established contemporaneously,” he asserted.

Russo, however, points to inconsistent quality standards for cannabis that can lead to inconsistent findings.

“It remains extremely difficult for consumers or their caregivers to gain access to the most effective and highest quality cannabis-based medicines,” Russo explained. “The only way to do this is by mandating that full analytical and safety information, including complete cannabinoid and terpenoid profiles, be available at the point of sale through analytical certificates on current batches. This will need to be coupled with better education on the pharmacological benefits of the various cannabinoid and terpenoid constituents.”

The Entourage effect is a very interesting phenomenon and by all accounts will be a very hot topic in the cannabis world. The good news for you is that you can also try the entourage effect on our strains.