What is the Entourage Effect?

The Entourage Effect: How Cannabinoids & Terpenes Work Together
If you’ve read any cannabis news articles or blog posts in recent years, chances are you’ve come across the aptly named “entourage effect.”

No, it doesn’t refer to a group of weed enthusiasts that follow a cannabis plant around and attend social functions together. In this case, the term “entourage” is used more as a metaphor than a literal interpretation of the word.

The entourage effect is a term used to describe the synergistic effects of combining various chemical compounds found in cannabis.

Simply put, the entourage effect is a term used to describe the synergistic effects of combining various chemical compounds found in cannabis. Most commonly, it refers to the interaction between THC/CBD and other cannabinoids or terpenes.

Cannabinoids and Terpenes

Before we get into too much detail about the entourage effect, let’s review some basic terms that help define the chemical composition of cannabis.

Cannabinoids

Cannabinoids & the Entourage Effect

You might be familiar with THC and CBD, but did you know that these are only two of over 120 cannabinoids that occur naturally in the cannabis plant1?

Cannabinoids interact with the Endocannabinoid System (ECS), a system composed of chemical messengers (endocannabinoids) and binding sites (receptors) located throughout the human body which regulates diverse functions including pain, sleep and appetite.

THC is psychoactive and intoxicating. It’s the cannabinoid that causes the “high” feeling that many consumers experience after inhaling or ingesting cannabis.

CBD, on the other hand, is non-intoxicating. This helps explain the rising popularity of CBD in the medical realm, as many patients who wish to use cannabis for medicinal purposes do not want to feel “high.”

On their own, THC and CBD have demonstrated a broad range of potential therapeutic applications2. In some cases, however, they work best together. Keep reading to find out why.

Terpenes

Terpenes & the Entourage Effect

Have you ever opened a container of cannabis and immediately noticed a citrus aroma? Or perhaps you smelled a hint of pine, pepper or lavender.

The chemicals responsible for this diverse range of aromas are known as terpenes.

Terpenes are aromatic flavour compounds found in cannabis, as well as a plethora of other plants, fruits, herbs and spices.

In cannabis, terpenes develop in the resinous glands (trichomes) of the plant. They are believed to protect the cannabis plant by warding off predators with their scent.

Interestingly, they also possess certain therapeutic properties.

For example, pinene (also found in pine trees) may reduce inflammation, while linalool (also found in lavender) exhibits anti-anxiety effects3.

How Does the Entourage Effect Work?

So, we know that cannabinoids and terpenes can both produce certain effects on their own. But what about mixing different cannabinoids together, or combining cannabinoids with terpenes?

As it turns out, this isn’t a straightforward equation of 1 + 1 = 2. That is to say, combining THC with CBD doesn’t simply add the effects of CBD and THC together. Rather, THC and CBD interact with each other (and other cannabinoids like THCV, CBN and CBG) and terpenes to produce a synergistic effect – this is known as the entourage effect.

You might be wondering precisely which combination of cannabinoids and terpenes is ideal for treating a specific condition. Unfortunately, due to decades of prohibition and stigma against cannabis, research into the entourage effect is only just beginning. As such, we know very little about which cannabinoids and terpenes pair best together.

That said, some ground-breaking studies have provided insight into how the entourage effect works.

The Entourage Effect with Cannabinoids

One study looked at the effectiveness of THC in reducing cancer-related pain versus THC and CBD combined, and found that “the THC:CBD combination showed a more promising efficacy profile than the THC extract alone4.”

These results are intriguing, as they provide further evidence of an entourage effect from combining different cannabinoids together.

Besides potentially amplifying THC’s analgesic properties, CBD produces another interesting cannabinoid entourage effect: it has been shown to reduce the psychoactive effects of THC.

The mechanism for how this works is complex, but it is thought that CBD interacts indirectly with the body’s CB1 receptors (part of the ECS) in a way that negatively affects the ability of THC to bind to these receptors5.

These are just a couple examples of the entourage effect from combining cannabinoids. It’s important to remember, though, that most cannabis strains have been selectively bred to optimize THC or CBD content. As a result, little is known about the other 118+ cannabinoids – so you can imagine the numerous other potential cannabinoid entourage effects that may exist, but have yet to been studied.

The Entourage Effect with Terpenes

No discussion of the entourage effect would be complete without mentioning Dr. Ethan Russo’s seminal research paper, Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects.

Dr. Russo’s paper features a compelling summary of studies that have demonstrated the therapeutic effects of cannabinoids and terpenes, providing an overview of some of the best known (and most researched) chemical compounds in cannabis.

Since every terpene is unique in its chemical composition, each one offers something different in terms of effects. Most cannabis strains contain a variety of terpenes, making it nearly impossible to ascertain which cannabinoid-terpene pairings elicit a terpene entourage effect.

With that in mind, research into terpenes provides some clues.

For example, Dr. Russo contends that “data would support the hypothesis that myrcene is a prominent sedative terpenoid in cannabis, and combined with THC, may produce the ‘couchlock’ phenomenon of certain chemotypes3.”

If THC + myrcene = couchlock, what other terpene entourage effects are possible?

As research into the entourage effect is still in its infancy, only time will tell. But it’s entirely possible that in the future, instead of classifying strains by physical characteristics (i.e. sativa versus indica), we will instead think of cannabis in terms of their chemotype (chemical profile) – a much more accurate predictor of the strain’s effects.

References:

  1. Morales P, Hurst DP, Reggio PH. Molecular Targets of the Phytocannabinoids: A Complex Picture. Progress in the Chemistry of Organic Natural Products, 2017;103–131.
  2. Freeman TP, Hindocha C, Green SF, Bloomfield M. Medicinal use of cannabis based products and cannabinoids. BMJ, 2019;365-1141.
  3. Russo, EB. Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects. BJP, 2011;163(7);1344–1364.
  4. Johnson J R, Lossignol D, Ganae-Motan ED, Fallon MT. 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. JPSM, 2010;39(2);167-179.
  5. Laprairie RB, Bagher AM, Kelly ME, Denovan-Wright EM. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. BJP, 2015;172(20);4790-805.