What is the entourage effect? How does it all work? We will take a look at how cannabinoids work together as a team to boost CBD's benefits.
As we experience the legalization of cannabis and its growth in popularity, people are becoming more curious about using it for themselves.
The main industry focus surrounds cannabidiol (CBD) and tetrahydrocannabinol (THC); these two natural compounds are found in cannabis plants.
Let's start by comparing the two major cannabinoids in cannabis:
CBD is found primarily in extractions from hemp, and it does not have any psychoactive properties. It's sold in gels, gummies, oils, supplements, extracts, and more.
THC is the primary psychoactive compound in marijuana that gives users the feeling of being high. It can be consumed by smoking marijuana or ingesting oils, edibles, tinctures, and capsules.
Research has shown that both of these two compounds interact with your body's endocannabinoid system, but they have very different effects.
What are THC-Only and CBD-Only Medicines?
THC-only medicines refer to a synthetic extraction of THC. Two common examples of THC-only medications are Cesamet (nabilone) and Marinol (dronabinol).
When pure, synthetic THC options became available, as with Marinol in the mid-1980s, scientists hoped and expected that they would work just as well as cannabis. However, scientists soon learned that patients preferred real cannabis over synthetics.
According to a 2011 survey surrounding patients’ preferred forms of consumption, out of nearly 1000 patients in the study, less than 2% of participants preferred synthetic THC over other methods.
So, while these synthetic varieties are technically legal, and have been prescribed to treat nausea related to cancers, their overall efficacy is questionable.
The other point to consider is how quickly a pill works in the body versus an inhaling the medicine through smoke or vape, methods which take effect almost instantly. The speed at which drugs enter the bloodstream is called bioavailability.
The science here also didn’t take into account the nearly 100 other compounds within cannabis, which may offer other helpful effects. Most notably, a compound is known as Cannabidiol (CBD), which is now understood to modulate the psychoactive effects of THC on the human body.
On the other hand, CBD, considered a significant cannabinoid while accounting for nearly 40% of hemp’s extracted volume, has been shown to bind with a wide variety of endocannabinoid receptors within the human body. This results in many beneficial physiological effects.
CBD is not, by itself, a cure-all, by any stretch, but it does share many medical benefits with THC. Both cannabinoids may provide relief from similar conditions, but CBD does not cause the euphoric or psychoactive effects most attributed to THC and marijuana. It is due to the lack of these side effects that many people prefer to use CBD over THC.
Even though CBD-only medicines have proven to help many patients who have epilepsy, as with FDA-approved Epidiolex, research has shown when combining various cannabinoids; their combined benefits are stronger than each on their own.
This is in no way an argument against using synthetic medicines or an effort to dissuade patients from trying them, especially when the law limits access to better alternatives. I am merely pointing out that as we make legislative leaps forward to full legalization, we learn there is more to whole plant medicine than individual extracts.
Let’s look more into that now.
What Makes "Whole Plant Medicine" Different?
Before we determine what makes whole plant medicine different from single-molecule extracts, let’s define what whole plant medicine is for a better context.
“Whole plant medicine” describes medicines that utilize a full spectrum of compounds, cannabinoids, and terpenes to provide the most therapeutic benefits the plant has to offer.
Cannabinoids and Terpenes Work Together
Both the cannabinoids THC and CBD are available in isolated forms, and so are terpenes. You can buy isolated terpene extracts to add to foods, and even add them to cannabis and marijuana products.
Combining terpenes with cannabinoids results in better efficacy when compared to isolates alone. For this reason, many medicinal cannabis experts advocate for whole plant medicine, rather than taking specific compounds in isolation.
In Ethan Russo, M.D.'s research "Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects," he explains how combining Cannabinoids and Terpenes work together.
Let's take a look at inflammation, for example.
Most Effective Cannabinoids
Most Effective Terpenoids
Most Effective Cannabinoids
Most Effective Terpenoids
Notice how many cannabinoids have been shown to assist in treating inflammation. When we only rely on a single molecule, we lose out on the potential assistance these other cannabinoids have to offer.
Similarly, when we take a look at the terpenes that are best suited for treating inflammation, we learn that using an isolate for inflammation may not be the best solution. If you are not fully grasping why terpenes are as crucial as they are, please take a look at this article, where we discuss terpenes in greater detail.
Suffice it to say that terpenes exist in all sorts of natural plant extracts, not just cannabis. Unfortunately, many extractions, especially those using solvents, remove these helpful terpenes from the end product.
NOTE: Whole plant medicines extracted from a CO2 extraction process are the most potent for medicinal applications.
To be brief, when we look at the terpenes pinene, myrcene, and caryophyllene, it is found that the combination may help unravel anxiety when taken together.
Also, mixing the terpenes linalool and limonene with the cannabinoid CBG shows promise in treating MRSA.
THC plus CBN yields enhanced sedating effects which help with sleep.
Linalool and limonene combined with CBD are being examined as an anti-acne treatment.
There are countless examples.
Now, due to the fact, there are more cannabinoids and terpenes in whole-plant extracts, the potential breadth of conditions and symptoms that may be treated with it are more comprehensive than with single cannabinoid extracts as discussed above.
Furthermore, herbalists have used whole plant medicines for thousands of years within ancient Ayurvedic and Traditional Chinese Medicinal practices.
The whole plant CBD's anti-inflammatory and anti-pain responses increase in higher doses, whereas the purified and isolated CBD results in a bell-shaped dose-response, meaning it loses effectiveness when the dosage is below or above a certain amount.
All roads point to whole plant medicine over isolates.
What is the Entourage Effect?
The entourage effect is a phenomenon that results when multiple components within cannabis interact with the human body's endocannabinoid system to produce a stronger influence than any one of those components alone.
Each of these cannabis compounds synergistically enhance the natural properties of other cannabis compounds. This means that cannabis compounds will deliver a multiplying effect together more than a single compound could on its own.
Many cannabinoids have been found to work together with THC to produce relief that is often reported by cannabis users. Most notably, cannabidiol (CBD) has been shown to modulate the effect that THC has on the human body the most.
Cannabinoids, Terpenes & The Entourage Effect
Plants in the Cannabis Sativa L. species, including both hemp and marijuana, contain hundreds of chemical compounds; among these are cannabinoids and terpenoids. These all have their ways of interacting with the human body.
The phrase "entourage effect" was first coined in 1998 by a group of scientists led by the renowned Israeli biochemist Dr. Raphael Mechoulam. It has come back into the limelight thanks in large part to Dr. Ethan Russo's paper, as discussed above.
In 2008, Russo reported, "Good evidence shows that secondary compounds in cannabis may enhance the beneficial effects of THC" while reducing the adverse side effects of THC.
As we covered earlier, science has identified over 120 different cannabinoids within cannabis, with discoveries occurring regularly!
The unique effects and properties of each cannabinoid are enhanced through the entourage effect, naturally delivering more significant relief than they would have individually. Even the lesser-known and less studied cannabinoids play an active role in hemp's efficacy as a medicine.
Cannabis contains resin glands in which Terpenes are produced. Terpenes are why there are so many unique aromas associated with marijuana and can stimulate a variety of beneficial physiological and psychological effects by stimulating receptors in our olfactory system (sense of smell).
We refer back to Dr. Russo's research that specific terpene combinations result in exciting and unique results in patients. It makes sense to combine these terpenes with THC and CBD products for particular outcomes.
The Entourage Effect
Due to the combined efforts, these scientists and researchers have paved the way forward. Many cannabis proponents conclude that "full-spectrum" oils containing all the contents from cannabis with added terpenes from cannabis and others make for the most effective cannabis-based medicine.
Thanks to their research, we know that when we combine all of these ingredients, we don't just get the sum of all their parts, but we end up with a compounding effect in which each piece amplifies the others', making it more effective in addressing unwanted symptoms.
The Entourage Effect in Different CBD Products: A Comparison
Depending on the extraction method, what is left in, and what is left out can have a tremendous impact on a CBD product's entourage effect.
CBD isolate products do not contain any other cannabinoids or terpenes, and will not deliver any compounding benefits touted by the entourage effect. Even if CBD isolates can provide some therapeutic effects, unless the user is constrained to using pure CBD only due to legal reasons, the potential impact is significantly limited versus the potential benefits offered by a broad or full spectrum option.
This contains CBD isolated from other cannabinoids with the addition of specific terpenes for specific effect. This does not contain THC or any other cannabinoids. This is less effective than Broad Spectrum CBD, but more effective than CBD in Isolated form.
Broad Spectrum CBD
This contains a broad range of cannabinoids and terpenes without the psychoactive properties of THC; it delivers a limited entourage effect since it does not also contain THC, but it is still more effective than a CBD isolate.
Full Spectrum CBD
This contains a full range of cannabinoids and terpenes including the legally allowed quantities of THC; it delivers a significant entourage effect difference over CBD isolates with a minor benefit over broad-spectrum products.
Whole Plant Medicine
Whole plant extracts will deliver the most potent and powerful entourage effect over all other options. This is truly using cannabis to its fullest medicinal potential since nothing is removed and in some instances, terpenes are added for enhanced effect.
Most medicine practitioners prefer a one-to-one relationship with illness and medication.
When we discuss synthetic medications, isolated treatment options may work well, but "Whole Plant Medicine" works better since it uses everything the plant has to offer within the product.
A single compound can treat a specific ailment, but cannabis therapy takes advantage of the whole plant to create the entourage effect and also provide preventative care before symptoms of an unknown illness take hold.
Today, most cannabis researchers' advise to doctors is that they should reject the idea of creating a single potent drug to treat an isolated problem; they believe that western medicine should return to a philosophy of preventative holistic treatment that targets the whole body's improved function with a natural plant.
What do you think?
Hazekamp, A., Ware, M., Muller-Vahl, K., Abrams, D. and Grotenhermen, F. (2013). The Medicinal Use of Cannabis and Cannabinoids—An International Cross-Sectional Survey on Administration Forms. Journal of Psychoactive Drugs, 45(3), pp.199-210.
Niesink, R. and van Laar, M. (2013). Does Cannabidiol Protect Against Adverse Psychological Effects of THC?. Frontiers in Psychiatry, 4.
Russo, E. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology, [online] 163(7), pp.1344-1364. Available at: https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.2011.01238.x [Accessed 6 Oct. 2019].
Ben-Shabat, S., Fride, E., Sheskin, T., Tamiri, T., Rhee, M., Vogel, Z., Bisogno, T., De Petrocellis, L., Di Marzo, V. and Mechoulam, R. (1998). An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. European Journal of Pharmacology, 353(1), pp.23-31.
McPartland, J. and Russo, E. (2001). Cannabis and Cannabis Extracts. Journal of Cannabis Therapeutics, 1(3-4), pp.103-132.
Rasoanaivo, P., Wright, C., Willcox, M. and Gilbert, B. (2011). Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions. Malaria Journal, 10(S1).
Dr. Sanjay Gupta, C. (2014). Medical marijuana and 'the entourage effect' - CNN. [online] CNN. Available at: http://www.cnn.com/2014/03/11/health/gupta-marijuana-entourage/ [Accessed 6 Oct. 2019].