Is the Cannabis Entourage Effect Real?

Some of you may have already heard about the cannabis entourage effect. This phenomenon refers to the combination of all the components of cannabis, where cannabinoids and terpenes interact with each other and provide greater benefits to the body than when used separately. The entourage effect is also called “whole plant medicine” or “whole plant synergy.” The idea is that the entire cannabis flower offers health benefits that individual compounds and cannabinoids alone cannot provide.

Professors Raphael Mechoulam and Shimon Ben-Shabat first presented arguments in favor of whole plant synergy in 1998. Their research showed that the body’s endocannabinoid system responds more favorably to whole cannabis extracts, increasing the activity of the two main endocannabinoids, THC and CBD. This may explain why whole plant medicines are often more effective than drugs containing only isolated plant molecules. Numerous studies published in recent years have begun to deepen our understanding of this phenomenon.

What Do We Really Know About the Entourage Effect?

There is evidence that some cannabinoids enhance the effects of other cannabinoids. For example, THC can improve the therapeutic effectiveness of CBD. Lesser-known cannabinoids may also provide benefits.

In an in vitro study on breast cancer tissue in lab animals, the presence of lesser-known cannabinoids improved the experimental results.

“Cannabis extract was much more effective than THC isolate in destroying tumors and reducing their growth,” said Ethan Russo, MD, founder and CEO of CReDO Science. “The synergy of cannabis extract may be explained by the presence of significant amounts of cannabigerol (CBG) and tetrahydrocannabinolic acid (THCA) in the extract.”

A similar study also showed that using a whole plant extract with a high CBD content was more effective in treating severe epilepsy than isolated cannabidiol. Moreover, the required dosage was 20% lower.

Dr. Jordan Tishler, a cannabis expert and instructor at Harvard Medical School, believes the entourage effect has been proven, but is often overgeneralized.

“There is irrefutable evidence that, for example, CBD modulates the effects of THC at the main receptor site. So the entourage effect is real,” he said. “However, the consequences of the entourage effect have been extrapolated beyond the available data. The idea that other chemicals are important for CBD’s action is not currently supported.”

Tishler also states that the role of minor cannabinoids, such as CBG or CBN, has not yet been fully studied in relation to THC or CBD. Many molecules may play a role in supporting the effects of THC, but that does not mean they support other cannabinoids in the same way.

Scientists recognize these findings and therefore distinguish between two different types of the entourage effect:

• The entourage effect related to interactions between cannabinoids and terpenes.
• The entourage effect related to interactions among cannabinoids themselves and among terpenes themselves.

What About Terpenes?

Terpenes are believed to play a crucial role in the entourage effect. However, until recently, research on cannabinoids and terpenes was relatively limited. Many recent studies suggest that terpenes may not be as involved in the entourage effect as previously thought.

According to a study published in March 2020, terpenes present in cannabis may not contribute to the entourage effect at all. Researchers found no evidence that the five most common terpenes—myrcene, α- and β-pinene, β-caryophyllene, and limonene—contributed to the entourage effect by binding to the body’s cannabinoid receptors.

Another study conducted the same year also supported the hypothesis that cannabinoids and terpenes do not work together in the body.

However, as is often the case with cannabis research, these results are not definitive. In a study conducted in April 2020 on mice, three common cannabis terpenes—humulene, pinene, and geraniol—were shown to activate the CB1 receptor. The CB1 receptor is responsible for inducing physiological responses such as reduced pain perception. Scientists suggested that terpenes may offer therapeutic benefits.

According to Tishler, there is not enough evidence to show that terpenes contribute to whole plant cannabis synergy. However, this does not mean these aromatic compounds are ineffective. There are two exceptions: myrcene, which causes drowsiness but does so independently, not as part of the entourage effect; and β-caryophyllene, which may be important for pain control.

Conclusion

Tishler asserts that the entourage effect is a real phenomenon, but it is often misunderstood.

“Currently, our understanding of the interactions involved in the entourage effect is quite limited,” he said. “There is not enough data to make specific products or recommendations based on other cannabinoids or terpenes. But that does not mean that non-whole plant products have no advantages.”

At the clinical level, products containing pure THC or CBD seem less effective than whole cannabis, suggesting that other chemicals are indeed involved. It just remains unclear which ones and how they work, according to Tishler.