The entourage effect is the mechanism in which cannabinoids act synergistically with each other and numerous other compounds within the plant, such as terpenes, flavonoids and resins. The entourage effect was coined in the late 1990s by the famous Rafael Mechuolam, Shimon Ben-Shabat and their group of Israeli researchers. 

The discovery of cannabinoids’ ability to enhance and compliment each other has led to huge advances in extraction and formulation strategies. While the term ‘entourage effect’ is primarily used in the cannabis industry, this phenomenon is thought to occur in a wide range of botanical medicines. 

How does the entourage effect work?

In the realms of recreational cannabis, the entourage effect is touted for its capacity to enhance the effects of THC and contribute to the psychoactive and somatic experiences of cannabis. 

However, in the medical setting, the synergistic action of cannabinoids and other plant compounds is appreciated for its propensity to alleviate symptoms of complex or difficult to treat conditions such as autoimmune, gastrointestinal and mood disorders.

At a physiological level, combinations of cannabinoids, terpenes and flavonoids can increase the activity of endogenous cannabinoids and interact with the body’s endocannabinoid system. 

Cannabinoids working together

Additionally, cannabinoids are thought to have a symbiotic action, the most well-known example of this is CBD’s action mitigating the psychoactive effects of THC. Terpenes also have their role in the entourage effect: to name a couple, 𝛽-myrcene as an anti-inflammatory and linalool with anticonvulsant activity. Both of these examples correspond with well-documented actions of CBD oil.

You could imagine the action of the entourage effect to be much like an orchestra. Each musician has great skill individually, their talent can operate in isolation or can have an entirely different impact when combined with other musicians in the orchestra.

Isolated cannabinoids vs formulations: beneficial results and side effects

For medical cannabis patients, the choice between isolated cannabis treatments and full or broad-spectrum formulations primarily is determined by the presenting condition. 

The drug Marinol has been on the market since the 1980s used as a potent appetite stimulant in treating anorexia as well as nausea and vomiting associated with cancer therapy. In the case of Marinol, isolated synthetic THC produces the desired effect in increasing hunger, yet is commonly associated with side effects such as paranoia and a subjective high. 

When taking formulations or whole-plant extracts, patients are ingesting a range of carefully measured cannabinoids, terpenes and other plant compounds. By choosing formulations prescribers can select products that are most suitable to the patient’s needs, in doing so utilising the potential benefits of the entourage effect.

Evidence for the entourage effect

In studies relating to human breast cancer cells in vitro, formulated extracts were compared to pure THC, with positive outcomes seen from the formulated treatment, rather than THC-only. The authors believed this may be attributed to the combined action of THC with minor cannabinoids, CBG and THCA.

Other evidence for the entourage effect’s impact in treating skin conditions, bacterial infections, mood and cognitive disorders is beginning to be uncovered. In contrast, a recent study has reported no differences when administering terpenes with phytocannabinoids in the context of activating cannabinoid receptors.

While there is little solid evidence for either side of the debate, a strong appetite for information on the topic continues to fuel clinical research.