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An Examination of the Entourage Effect

Leslie kahn

In this article I will define the Entourage Effect. I will discuss the different interactions that occur between the cannabinoids and terpenes in medical cannabis. I will also discuss single cannabis compound products vs full-spectrum products and explain some of the drawbacks of each.F

What Is the Entourage Effect? 

When the various cannabis compounds of cannabinoids, terpenes and flavonoids work together, they interact to create an enhanced product with unique effects and benefits. In other words, the whole is greater than the sum of the parts. Researchers are now understanding that the lesser known cannabinoids and terpenes all play important roles in the Entourage Effect. Until very recently, the existence of terpenes was not even on most people’s radar. These days, dispensary products list the percentages of the cannabinoid profile as well as the terpene profile.

2011 Paper on the Entourage Effect by Dr. Ethan Russo

One of the most important studies on the Entourage Effect was conducted by Dr. Ethan Russo, one of the most notable, highly-acclaimed neurologist and psychopharmacology researcher.

In his paper, Taming THC: Potential Cannabis Synergy and Phyto Cannabinoid-Terpenoid Entourage Effects, Dr. Russo investigated THC and CBD as well as several other phytocannabinoids. These included THCV, CBC, CBG, CBDV and CBN. He also investigated terpenes which he described as essential oil agents (EO). These included limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol.

He examined the following:
1. The interactions between the different cannabinoids
2. The interactions between the different terpenes
3. The interactions between the different cannabinoids and terpenes

Dr. Russo’s goal in doing this research was to find new approaches to treating the following disorders:

  • Anxiety
  • Dermatological disorders
  • Dementia
  • Drug dependency
  • Treatment-resistant depression
  • Pain
  • Cancer
  • Inflammation
  • Epilepsy

He was also very interested in finding industrial solutions for safer pesticides and antiseptics.


It is important to point out that the effects of terpenes on humans is based almost entirely on anecdotal information. Their interactions with THC have rarely been assessed as a result of scientific studies. There are some animal model terpene studies but those used such high doses of terpenes that it is not possible to extrapolate the results to human consumption in any meaningful way. But, things are changing for the better!


As you have already guessed, it is associated with a citrus aroma. Anecdotal information reports that it affects mood. It is also thought that limonene interacts with several different neurotransmitter systems such as the serotonin system, the adenosine system and the GABA system. These systems control alertness, mood and critical thinking.

Limonene Studies 

  • In a 2013 Brazilian study using a 14 day treatment of limonene on rodent models, researchers concluded that it reduced anxiety, depression and cholesterol levels.
  • A 2019 human study demonstrated that its inhalation lowered heart rate.

Three Clinical Studies on The Cannabinoid-Terpene Entourage Effect

The National Institutes of Health (NIH) granted Dr. Ryan Vandrey, Associate Professor of Psychiatry and Behavioral Sciences at Johns Hopkins University, funding for three clinical trials of the interactions between cannabinoids and terpenes.

First Trial: How Limonene Regulates the Effects of THC

In one of the most comprehensive studies of its kind, 20 healthy adults will make nine separate visits to a research unit. At each visit, they will vaporize THC only, limonene only, a combination of THC and limonene or a placebo. There are two different dosing levels of THC; 15 mg and 30 mg and two different dosing levels of limonene; 1 mg and 5mg.

The Expected Outcome of Cannabinoid-Terpene Interactions 

Researchers believe that such interactions may increase the permeability of the blood-brain barrier as well as affect the binding capacity of THC to CB1 receptors. It is thought that another common terpene, α-pinene, found in pine and other coniferous trees, may have the ability to counteract the short-term memory loss that often accompanies high dosages of THC.

Additional Factors Contributing To The Entourage Effect 

It may be possible that the combination of cannabinoids and terpenes affect different receptors or other cellular pathways to produce a better overall outcome. An example of this would be a multi-layered attack on inflammation by the different cannabis molecules. Some researchers posit that terpenes may enhance the ability of the body to better absorb or process cannabinoids.

Interaction of CBD and THC 

There is much anecdotal evidence that CBD counteracts the paranoia and anxiety that THC elicits in some consumers. Until there is more research of human trials, this claim cannot be scientifically substantiated.

Single Cannabis Compound Products 

There are many CBD only products and even some THC only products available for purchase. Single cannabis compound products do provide some benefits for some consumers. However, the overwhelming anecdotal evidence suggests that the myriad of chemical phenotypes of the cannabis plant work together to deliver many more benefits than each individual compound could possibly furnish by itself.

Full-Spectrum Products 

Both research and anecdotal evidence have shown that whole plant medicine is much more effective in treating medical conditions than single compound products. However, according to Jon Cooper, ebbu founder and a member of the Board of Directors at CaaMTech, most people’s understanding of the Entourage Effect is wrong. They think that by using the full spectrum of compounds that the end result will be better than using a single compound. The reality is that there are specific combinations of compounds that interact with the body’s receptors. The way in which different cannabinoids and terpenes are combined will produce dramatically different outcomes.

He cites the following example:
An individual receives pure THC which when applied to CB1 receptors and measured will elicit a 40% response. If the amount of THC is reduced and combined with very specific cannabinoids and terpenes in a specific ratio, the individual’s response will increase to over 80% with triple the potency.

With our current level of understanding of how cannabis compounds interact, full-spectrum products produce better overall results than single compound product. However, the more researchers learn about the nuances of the cannabis plant, the more adjustments that can be made to create even better strains.

Sources:, How Might Terpenes Contribute to the “Entourage Effect” of Cannabis? Mike Tagen, Terpenes and The Entourage Effect, Ebbu Founder Jon Cooper on Consistency in the Cannabis Market, July 15, 2019, Patricia Miller; Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT1A-receptors and reduces cholesterol after repeated oral treatment, BMC Complementary Medicine and Therapies, Feb. 23, 2013