What is the Entourage Effect

The Cannabis Entourage Effect Explained

The cannabis entourage effect is frequently mentioned in relation to CBD products. But what does it actually mean? Here’s a detailed explanation.

Gleb Oleinik Updated on July 27, 2021

You’ve probably heard the term “entourage effect.” It gets thrown around quite frequently in the CBD industry, but what does it mean?

The entourage effect is the idea that whole-plant cannabis preparations work better than those containing only THC or CBD. It’s the result of the synergy between the hundreds of active compounds found in the plant.

That’s why it’s thought best to use full-spectrum CBD products rather than those containing CBD isolate whenever possible.

Read on to learn more about the entourage effect, how it was discovered, how it works, and why it’s so important.

What is the Entourage Effect?

The entourage effect is the theory that cannabis provides the most benefits when used as a whole plant extract. It’s what happens when you use all of the cannabinoids, terpenes, and other active phytochemicals in cannabis together.

You’re getting not just the individual benefits of each compound in this entourage, but, more importantly, their synergistic relationships with each other. As the popular saying goes, “the whole is greater than the sum of its parts.”

One of the best examples of the entourage effect is the synergy between THC and CBD. If you were to take pure THC, especially in large doses, there’s a good chance you’d feel its notable mind-altering effects. But when you pair it with CBD, something happens.

CBD reduces THC’s intoxicating effects such as anxiety and psychosis. ¹ That’s why cannabis — and especially strains rich in CBD — is less intoxicating than pure THC.

Not only that but CBD and THC also strengthen each other’s beneficial effects. For example, a 2010 study in patients with treatment-resistant cancer pain found that combining THC with CBD greatly enhanced its pain-relieving therapeutic effects.

Individuals in the study treated with THC on their own did not differ significantly from the placebo treatment group. However, 43% of the people in the THC plus CBD group had a 30% or greater improvement in pain. ²

It’s also important to note that the entourage effect applies to both marijuana and hemp, the two main types of cannabis. Whereas marijuana is rich is in THC and low in CBD, hemp is high-CBD and low-THC. Aside from that major difference, they both contain similar compounds.

The Discovery of the Entourage Effect

The entourage effect was first proposed in 1998 by Israeli researchers Raphael Mechoulam and Shimon Ben-Shabat. They coined the term after performing a study of 2-AG, one of the main endocannabinoids made by our bodies.

The researchers noticed that when 2-AG was given to mice alongside other closely related molecules, its effects were stronger. ³ Yet, by themselves, these related endocannabinoid compounds showed no activity.

In the years since, numerous studies have provided further evidence for the entourage effect.

The Cannabis Entourage

When we think of cannabis, we tend to associate most of its effects with THC and CBD. It’s easy to think this way because THC and CBD are the two most abundant active compounds in the plant and have received the most attention from researchers and the media.

However, cannabis plants contain dozens of other cannabinoids, as well as many other classes of compounds, including terpenes, flavonoids, fatty acids, minerals, and vitamins. All in all, cannabis plants are made up of over 400 chemical compounds. ⁴

All of them can have benefits and more importantly modify or amplify each other’s effects — what scientists call synergy. Let’s take a closer look at these different chemicals and how they contribute to the entourage effect.

Cannabinoids

Cannabinoids are believed to play a pivotal role in the entourage effect. In a nutshell, cannabinoids can enhance each other’s effects when used together. We already discussed the prime example of this: the synergy between THC and CBD.

Another lesser-known example of cannabinoid synergy occurs between THC and cannabinol (CBN). When researchers studied the effects of these two cannabinoids, CBN did not produce any notable effects by itself.

Yet, when taken together with THC, it enhanced feelings of dizziness, drowsiness, and drunkenness. ⁵

Keep in mind that the cannabis plant contains over 120 different cannabinoids, most of which (like CBN) are considered “minor” because they’re present in very small quantities. All of these cannabinoids could potentially be interacting or indirectly with THC, CBD, and each other. ⁶

That means the list of potential cannabinoid synergies that we don’t yet know about is immense. And we haven’t even touched on terpenes.

Terpenes

Without a doubt, terpenes are the most overlooked component of the entourage effect. These natural aromatic compounds are found in many plants – including fruits, trees, spices, and cannabis.

Terpenes are responsible for the unique aromas of plants, such as the distinct smells of different strains of cannabis. For example, pinene is one of the main compounds responsible for the characteristic smell of pine trees.

Terpenes contribute to the entourage effect not only through their distinct effects on health but also by synergizing with cannabinoids. Examples of cannabis terpenes and various studies highlighting their potential benefits include:

  • Linalool – may have sedative, anxiolytic (anxiety-reducing), ⁷ anti-inflammatory, and antioxidant effects that can contribute to the effects of CBD and other cannabinoids. ⁸
  • Myrcene – may provide anti-inflammatory, muscle-relaxing, ⁹ sedative, and anticancer ¹⁰ properties and may also make it easier for cannabinoids to cross the blood-brain barrier, enhancing their effects. ¹¹ It might also contribute to the “couch lock” often experienced by cannabis users. ¹²
  • Pinene – may have anti-inflammatory, ¹³ bronchodilating, ¹⁴ and memory-aiding properties. It may also help offset the short-term memory impairment from THC intake. ¹⁵
  • Limonene – may have anxiolytic properties and pair well with CBD. ¹⁶
  • Caryophyllene – may provide anti-inflammatory effects and stimulate CB2 receptors. ¹⁷ It’s also been shown to reduce alcohol intake in a mouse study, potentially pairing well with efforts to use CBD for anti-addiction. ¹⁸

 

Again, these are just a few preliminary studies highlighting various examples of terpenes. There are many other terpenes and related compounds called terpenoids in cannabis, all of which can have potential synergies with cannabinoids and other compounds present in the plant.

Other Phytochemicals

Although cannabinoids and terpenes play the most important role in the entourage effect, we shouldn’t forget the remaining chemicals in cannabis. These include flavonoids, fatty acids, minerals, vitamins, and other phytochemicals such as chlorophyll.

For example, it’s common knowledge that fatty acids, minerals, and vitamins play an essential role in human health, so we know they can have effects of their own. But it’s also possible that they could synergize with cannabinoids or terpenes in some way.

At this time, research is limited about how these compounds contribute to the cannabis entourage effect. However, scientists are continuing to explore their effects as it’s possible that they do play a role.

The Endocannabinoid System

Most of the effects of cannabis are the result of the interaction between cannabinoids and the endocannabinoid system (ECS). This system is composed of three key elements:

  1. Endocannabinoids — cannabinoids made by our bodies
  2. Metabolic enzymes that make and break down endocannabinoids
  3. Cannabinoid receptors (CB1 & CB2) that respond to cannabinoids

 

The ECS is thought to play a large role in maintaining homeostasis in our bodies, a scientific term for a state of internal balance where everything is functioning as it should — not too much and not too little.

Put simply, the ECS helps maintain your overall health by regulating major processes, including immunity, inflammation, pain, sleep, mood, cognitive function, metabolism, and stress. ¹⁹

Although the ECS is activated by our body’s endocannabinoids, it can also respond to phytocannabinoids — cannabinoids coming from plants such as cannabis. For example, some phytocannabinoids, such as THC, can bind directly to the body’s cannabinoid receptors.

Others, like CBD, don’t bind to cannabinoid receptors. Instead, CBD can change how the CB1 receptor responds to other cannabinoids. ²⁰ It remains to be researched and confirmed whether this can explain how CBD may synergizes with THC and potentially counteracts its psychotropic side effects.

CBD can also suppress the enzyme that breaks down endocannabinoids, potentially enhancing their effects. ²¹

Full and Broad Spectrum CBD Oils vs Isolates

You may have heard that there are three kinds of CBD oil: full-spectrum, broad-spectrum, and isolate.

Full-spectrum and broad-spectrum oils are both whole-plant extracts, which means they contain all of the beneficial components of hemp and make use of the entourage effect.

The only difference between these two extracts is that full-spectrum CBD contains small amounts (<0.3%) of THC, which is completely removed in broad-spectrum CBD.

Meanwhile, isolate is a pure form of CBD without any other cannabis compound. As such, it doesn’t benefit from the entourage effect.

This explains why it’s commonly recommended to use CBD products formulated with full-spectrum or at least a broad-spectrum CBD extract over those made with isolate.

Of course, whole plant CBD products are not without their downsides. For example, full-spectrum CBD might not be the best choice for someone who’s extremely sensitive to THC or has to pass drug tests for work.

However, when we’re talking about the effectiveness of CBD for various purposes, whole-plant CBD tends to be the winner compared to other hemp plant extracts.

Possibly due to the entourage effect, full and broad-spectrum CBD products tend to produce greater desired effects, require smaller doses, and have a smaller chance of causing side effects than those formulated with CBD isolate. ²²

Whole-Plant Medicine: The Way Of the Past and the Future?

To sum up, the entourage effect is the proposed scientific theory that the effects of cannabis may be most effective when used in the form of a whole-plant extract.

Perhaps what’s most interesting about this idea is that it lines up with anecdotal evidence throughout history. If we look back at thousands of years, we can see that human civilization always used cannabis and other herbal medicines in their whole-plant form.

These herbal remedies must carry some merit, or we wouldn’t find written and archaeological records of their use. In that sense, the entourage effect may be more of a rediscovery of one of nature’s greatest gifts to mankind.

Which raises an important question for the future of healthcare: is the single-molecule approach championed by modern medicine, where most pharmaceutical drugs contain a single active compound, taking us in the wrong direction?

References

1. Niesink, Raymond JM, and Margriet W. van Laar. “Does cannabidiol protect against adverse psychological effects of THC?.” Frontiers in psychiatry 4 (2013): 130.

2. Johnson, Jeremy R., et al. “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.” Journal of pain and symptom management 39.2 (2010): 167-179.

3. Ben-Shabat, Shimon, et al. “An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity.” European journal of pharmacology 353.1 (1998): 23-31.

4. Atakan, Zerrin. “Cannabis, a complex plant: different compounds and different effects on individuals.” Therapeutic advances in psychopharmacology 2.6 (2012): 241-254.

5. Karniol, Isac G., et al. “Effects of Δ9-tetrahydrocannabinol and cannabinol in man.” Pharmacology 13.6 (1975): 502-512.

6. Morales, Paula, Dow P. Hurst, and Patricia H. Reggio. “Molecular targets of the phytocannabinoids: a complex picture.” Phytocannabinoids. Springer, Cham, 2017. 103-131.

7. Costa, Celso ARA, et al. “Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT 1A-receptors and reduces cholesterol after repeated oral treatment.” BMC complementary and alternative medicine 13.1 (2013): 42.

8. Sabogal-Guáqueta, Angélica Maria, Edison Osorio, and Gloria Patricia Cardona-Gómez. “Linalool reverses neuropathological and behavioral impairments in old triple transgenic Alzheimer’s mice.” Neuropharmacology 102 (2016): 111-120.

9. Pacher, Pál, Sándor Bátkai, and George Kunos. “The endocannabinoid system as an emerging target of pharmacotherapy.” Pharmacological reviews 58.3 (2006): 389-462.

10. Sobral, Marianna Vieira, et al. “Antitumor activity of monoterpenes found in essential oils.” The Scientific World Journal 2014 (2014).

11. Hartsel, Joshua A., et al. “Cannabis sativa and Hemp.” Nutraceuticals. Academic Press, 2016. 735-754.

12. Russo, Ethan B. “Taming THC: potential cannabis synergy and phytocannabinoid?terpenoid entourage effects.” British journal of pharmacology 163.7 (2011): 1344-1364.

13. Gil, M. L., et al. “Comparative study of different essential oils of Bupleurum gibraltaricum Lamarck.” Die Pharmazie 44.4 (1989): 284-287.

14. Falk, Agneta A., et al. “Uptake, distribution and elimination of α-pinene in man after exposure by inhalation.” Scandinavian Journal of Work, Environment & Health (1990): 372-378.

15. Perry, Nicolette SL, et al. “In?vitro inhibition of human erythrocyte acetylcholinesterase by Salvia lavandulaefolia essential oil and constituent terpenes.” Journal of pharmacy and pharmacology 52.7 (2000): 895-902.

16. Carvalho-Freitas, Maria Isabel Roth, and Mirtes Costa. “Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L.” Biological and Pharmaceutical Bulletin 25.12 (2002): 1629-1633.

17. Gertsch, Jürg, et al. “Beta-caryophyllene is a dietary cannabinoid.” Proceedings of the National Academy of Sciences 105.26 (2008): 9099-9104.

18. Al Mansouri, Shamma, et al. “The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice.” Pharmacology Biochemistry and Behavior 124 (2014): 260-268.

19. Aizpurua-Olaizola, Oier, et al. “Targeting the endocannabinoid system: future therapeutic strategies.” Drug discovery today 22.1 (2017): 105-110.

20. Chung, Hery, Angélica Fierro, and C. David Pessoa-Mahana. “Cannabidiol binding and negative allosteric modulation at the cannabinoid type 1 receptor in the presence of delta-9-tetrahydrocannabinol: An In Silico study.” PloS one 14.7 (2019): e0220025.

21. Leweke, F. M., et al. “Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.” Translational psychiatry 2.3 (2012): e94-e94.

22. Russo, Ethan B. “The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain.” Frontiers in plant science 9 (2019): 1969.


Gleb Oleinik

Gleb Oleinik is a freelance CBD & cannabis writer from Vancouver, Canada. He’s read thousands of studies about cannabinoids and other beneficial natural compounds, helping him translate complex science into plain language. He’s also written third-party lab test reports of CBD products and knows the industry inside and out. When he’s not writing, Gleb likes to spend his time in the gym and out in nature.

Frequently Asked Questions

The entourage effect doesn’t really produce any discernible feeling. However, its overall impact is much more complex and varied than isolated THC or CBD because you’re simultaneously experiencing the individual effects and synergies of dozens of compounds.