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An Analysis of the Entourage Effect

May 5, 2020 in Cannabinoids

If you have been a medical cannabis user for some time, you are most likely familiar with the term Entourage Effect. It explains why it is more beneficial to use products which contain an assortment of cannabinoids and terpenes when choosing medical cannabis products. I will be citing some studies that substantiate this theory and will touch on the downsides of using single compound and full spectrum products.

What is the Entourage Effect?

The term Entourage Effect was first coined in 1998 by a group of cannabis researchers which included the “Father of Cannabis Research,” Dr. Raphael Mechoulam, an Israeli biochemist, who in 1964 identified THC, anandamide and 2-AG .

It refers to the synergy between all the compounds of medical cannabis, cannabinoids, terpenes, flavonoids and other phytochemicals, which results in an overall enhancement effect as they interact with one other. The way the compounds influence each other determines how effective your medication is.

Since this is a fairly new concept, there is not a lot of scientific research to substantiate this claim. It is also important to note that there are dozens of different possible combinations between the many cannabinoids, terpenes, flavonoids and phytochemicals that exist in medical cannabis.

The leading research study, Taming THC: Potential Cannabis Synergy and Phyto Cannabinoid-Terpenoid Entourage Effects, that is constantly cited, comes from Dr. Ethan Russo, one of the most notable and highly acclaimed cannabis researcher in his field. In his 2011 paper, Dr. Russo investigated the symbiotic relationship between cannabinoids and terpenes with the goal of finding the best combinations to treat pain, cancer, bacterial infections, inflammation, anxiety, addiction, epilepsy and treatment-resistant depression.

In addition to THC and CBD, Dr. Russo’s research also targeted other cannabinoids; THCV, CBDV, CBG, CBC and CBN.

He also examined the interaction of cannabinoids with the folllowing terpenes:
Limonene, myrcene, α-pinene, linalool, ß-caryophyllene, caryophyllene oxide, nerolidel and phytol

It is interesting to note that Dr. Russo cited some ancient antidotes used to relieve the unwanted psychotropic effects of THC. These include:
1. Lemon
2. Calamus plant roots
3. Pine nuts
4. Black pepper

Prior to that paper, in 2008, Dr. Russo had written that his research led him to discover that some of the lesser compounds in medical cannabis enhanced the effectiveness of THC. He also realized that they reduced the intense psychotropic effects of THC which some people find unpleasant.

Cannabinoid Interactions

The Entourage Effect of THC and CBD: British Study

In a 2010 British study conducted at Severn Hospice, Shrewsbury, UK, researchers compared the effects of cannabis extracts on patients with cancer pain using the following; THC only, 1:1 ratio of THC: CBD, and a placebo. This was a randomized, double-blind, placebo controlled, parallel group study. The subjects had advanced cancer pain that was not relieved by strong opioids. Those who received 1:1 THC: CBD experienced the most beneficial outcome. Twice as many patients reported a pain reduction of more than 30% from their baseline pain assessment when compared to those who received THC only and the placebo.

CBD May Mitigate the Effects of THC

There is much anecdotal information to corroborate the claim that CBD will mitigate the psychotropic effects of THC, including anxiety, paranoia cognitive impairment, increased risk of developing chronic psychosis or drug addiction. This information is very helpful for those who are new to using edibles and have unwittingly eaten a product with more THC than they can handle. While there is some animal model research to support this evidence, unfortunately, there are no human trials to support it.

CBN Interaction with THC

Dr. Russo concluded in his research that adding CBN to THC will enhance its sedation effects.

Terpene-Cannabinoid Interactions

1. Adding myrcene to THC overcomes a resistance to the blood-brain barrier, making it easier for other compounds to pass through it.
2. The addition of pinene counteracts any compromise of memory and cognition activities resulting from consuming THC.
3. CBG in combination with linalool and limonene treats MRSA
4. CBD in combination with linalool and limonene treats acne and other skin problems

Terpene Interactions

Pinene, myrcene and caryophyllene when combined have been seen to relieve long-term anxiety.

Single Cannabinoid Compound Products

The most popular single cannabis compound product is CBD. It gained a huge amount of popularity in 2011 when the Stanley Brothers of Colorado created Charlotte’s Web to treat Charlotte Figi’s Dravet Syndrome, an intractable form of epilepsy. It contained a ratio of CBD:THC of 30:1. In the past 9 years, the CBD market has exploded in the US with millions of products for sale online. While it was life-changing for Charlotte in helping to control her 300 seizures a day, much has been learned since then about the relationship between CBD and THC. Even those who are not fans of the psychotropic effects of THC recognize that the addition of a significant amount of THC greatly enhances the benefits and efficacy of CBD for many medical conditions.

Full-Spectrum Products 

Full-spectrum cannabis products maintain the full profile of the cannabis plant. They contain a variety of cannabinoids, terpenes, flavonoids, proteins, phenols, sterols and esters. They do provide many benefits due to the Entourage Effect. However, as we gain more and more understanding of how the different compounds in cannabis interact, there are those that recognize that not all the synergistic effects are beneficial.

Jon Cooper, formerly of ebbu, now with CaaMTech, and his team have spent the last three years investigating the effects of individual cannabinoids and terpenes on receptor cells. They assessed the activity level in those cells when two or more cannabis compounds were present. What they discovered was that different combinations result in measurably different reactions from the receptor cells. In some cases, one compound enhances the effect of another. In other cases, it reduces the effect of another.

With full-spectrum products, different cannabinoids simultaneously have an effect on several different receptors in the body. While some of those cannabinoids are extremely beneficial, many of them are neither useful nor essential. In some cases, certain cannabinoids can result in the opposite of the desired effect.

Because of the nature of the cannabis plant, each plant, even from the same strain, has a slightly different combination of compounds.

Cooper compares the blind use of whole-plant products as throwing everything you can at every receptor, hoping for the best result.

With the current understanding of how cannabis compounds interact, using an array of different cannabinoids and terpenes provides a better outcome than using single cannabis compounds. However, it is interesting to consider that as researchers learn more, they will be in a position to “fine tune” the combinations of cannabis compounds for even better results.

Sources:, How Might Terpenes Contribute to the “Entourage Effect” of Cannabis? Mike Tagen, Terpenes and The Entourage Effect, THC & CBD: The Entourage Effect Explained Simply, Dr. Singh, Sept 2, 2018, Entourage Effect 2.0: The Entourage Effect Is Real, But Full Spectrum Cannabis Is Not The Answer, Jon Cooper, Aug 9, 2018; Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of the Efficacy, Safety and Tolerability of THC:CBD Extract and THC Extract in Patients with Intractable Cancer-Related Pain, Feb. 2010

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