The Guide To The Cannabis Entourage Effect

Cannabis is the most widely used "illegal drug" in the United States. Ironically, it's also one of the least researched. Just how is this contradiction possible?

In 1971, the federal government classified marijuana as Schedule I in the Controlled Substances Act. This means that cannabis was considered a substance with a high potential for abuse, with no currently accepted medical use. As a consequence, cannabis research was severely stifled.

Despite mountains of evidence to the contrary, cannabis remains a Schedule I narcotic in the US. Regardless, some research has moved forward despite this misguided legislation.

In 2018 the World Health Organization (WHO) published a study on "Drug Dependence" that covered the cannabinoids CBD, THC, Delta 9 as well as resins and extracts. However, it was inconclusive as to the entourage effect.

In 2020, a review of research to date found no evidence of the entourage effect. However, in 2021, a study from the University of Arizona found evidence that supports it.

So where does that leave us? Hmmm. The state of the science is, at best, inconclusive. But all of that begs the most basic question. What, exactly, is this elusive entourage effect?

What Is The Entourage Effect?

The cannabis plant contains numerous cannabinoids, terpenes, and flavonoids. The entourage effect is the theory that they work together synergistically to enhance or limit effects depending on the specific ratios of cannabinoids, terpenes, and flavonoids in a given cultivar. By way of example, many cannabis users believe that the cannabinoid CBD may balance the anxiety that some feel from the cannabinoid THC, resulting in improved relaxation.

While this example may be useful in understanding the entourage effect, it is also an oversimplification. There is so much more to the cannabis plant than CBD and THC.

What Compounds Contribute To The Entourage Effect?

To date, there have been more than 120 types of cannabinoids identified in the cannabis plant. And every one of those compounds may affect your endocannabinoid system.

What Are Cannabinoids?

Cannabinoids are found in the trichomes on the flowers of the female cannabis plant. The major cannabinoids include THC, CBD, CBG, CBC, CBN, and THCV.


Tetrahydrocannabinol ("THC") is psychoactive. It is the cannabinoid that makes you feel high. It may impact how the user thinks, feels, and perceives. It may also release dopamine to create euphoria, and affect how information is processed in the brain’s hippocampus, which forms new memories.


Cannabidiol ("CBD") may be derived from the cannabis or hemp plant. It is not psychoactive in the way that THC is, although many users report a calming effect and use it for treatment of insomnia and/or anxiety. CBD may also treat epilepsy and inflammatory diseases such as Crohn's.


Cannabigerol ("CBG") is a cannabinoid usually extracted from the cannabis plant. CBG is sometimes called the mother of all cannabinoids because other cannabinoids are obtained from cannabigerolic acid ("CBGA"), an acidic form of CBG.

Like CBD, CBG is considered non-psychoactive, but may improve feelings of happiness and/or motivation. It may also increase appetite, maintain the sleep cycle, and treat pain.


Cannabichromene ("CBC") effects the brain and nervous system and may ease swelling and pain. CBC may also inhibit the growth of microbes.


Cannabinol ("CBN") results from the degradation or heating of cannabis. It has mild psychoactive effects, and is often used as a sedative. It may also reduce pain, inflammation and increase appetite.


Tetrahydrocannabivarin ("THCV"), is non-psychoactive when consumed in low doses. THCV at high doses is psychoactive. It may also suppress appetite and treat diabetes.

What Are Terpenes?

Surprise. The entourage effect is about more than just cannabinoids. It's also about terpenes. Terpenes are natural, aromatic compounds in plants. They give plants their unique aromas, flavors, colors, and work with cannabinoids to create distinct effects depending on a cultivar's terpene profile.

By way of example, the terpene pinene may limit the memory loss caused by THC. Similarly, limonene may treat anxiety and depression.

There are approximately 400 types of terpenes in the cannabis plant. Some of of the more prominent terpenes include:

  • Beta-caryophyllene
  • Geraniol
  • Limonene
  • Pinene
  • Geraniol
  • Myrcene
  • Humulene
  • Ocimene
  • Terpineol
  • Bisabolol
  • Eucalyptol
  • Linalool
  • Phytol
  • Nerolidol

I know. That's a lot terpenes. And a lot of cannabinoids. That's a big part of what makes the entourage effect so challenging to quantify.

What cannabinoid is having what effect?

What terpene is having what effect?

How are these cannabinoids and terpenes influencing each other?

How do they influence each other when the ratios change?

The questions endless, but there's still one more variable to consider in the entourage effect: Flavonoids.

What Are Flavonoids?

Flavonoids refer to a class of compounds found in many plants, including cannabis. Notably, they are rich in antioxidents and may help the body defend against everyday toxins. They are divided into six subclasses:

  1. Anthocyanidins
  2. Flavan-3-ols
  3. Flavonols
  4. Flavanones
  5. Flavones
  6. Isoflavones

The flavonoids specific to cannabis are known as cannaflavins. Cannabis plants receive their pigmentation from flavonoids. Flavonoids may work together with terpenes and cannabinoids in the entourage effect.

What Are The Origins Of The Entourage Effect?

The entourage effect was initially proposed by Raphael Mechoulam, a chemist at the Hebrew University of Jerusalem, in 1998. He analyzed the gut, spleen, and brain of mice and found that certain compounds could enhance the effects of others. Thus, some cannabis researchers believe it's likely that the cannabinoids, terpenes, and flavonoids in cannabis may enhance each other. Likely. But not proven. Not yet, at least.

How Can These Compounds Create The Entourage Effect?

As previously stated, it’s complicated. We can’t focus on a single terpene, cannabinoid, or flavonoid to create the entourage effect in cannabis. They all work together, synergistically, and the possible combinations are literally limitless.

By way of example, THC in high doses may cause anxiety. CBD may decrease anxiety. The terpenes linalool and myrcene may also decrease anxiety, thereby boosting the effects of the CBD and limiting the effects of the THC. Add some CBN, and that anxiety reduction may take on a more sedative effect and assist with insomnia. That’s an entourage effect in full effect and we haven't even considered flavonoids.

Logic notwithstanding, more research is needed. A lot more. Tons. But that doesn't mean that you can't try to find an entourage effect that works for you.

Think about it this way: A cannabis is not the same. If you're an experienced consumer, you know that different cultivars affect you differently; and that different cultivars affect different people differently. What could account for that other than their unique cannabinoid, terpene, and flavonoid profiles

How Can You Get The Most Out Of The Entourage Effect?

The simple answer is by choosing whole plant or full spectrum cannabis products. These are both terms used to describe cannabis products in which the "full spectrum" of cannabinoids, terpenes, and flavonoids in the source material are present in the end product.

Are There Any Health Benefits?

More research is needed to determine the entourage effect's health benefits. However, when cannabinoids, terpenes, and flavonoids work together, the synergistic effects may make them work more effectively together than they do by themselves:

Again, as an example: A cannabinoid like CBD that may reduce inflammation may be enhanced by a terpene and flavonoid with the same effect. Wouldn’t it be nice to chuck that ibuprofin bottle? We think so too!

What Does The Scientific Community Think Of The Entourage Effect?

Well, we're finally back to where we started and the answer hasn't changed. There are very few studies on the entourage effect, and the studies that we do have are inconclusive. But there's one thing that advocates and skeptics do agree on, and that is that more clinical trials are needed to determine whether the entourage effect is the real deal.

A huge step in the right direction would be for the federal government to take cannabis off of Schedule I. This would create a more robust environment conducive to research on this complex plant that has already helped so many.

Get Your Cannabis Products From Panacea Wellness

At Panacea Wellness, you can find a wide array of high-quality cannabis products. Our dispensary is stocked with premium flower, concentrates, edibles, tinctures, vapes, and more!

Deep dive our fire concentrate collection with live resin, bubble hash, diamonds, wax, kief, sugar, and RSO.

Our edible selection is also fat with fresh baked goodies, gummies, chews, and refreshing cannabis powered drinks.

Panacea is proud to serve both medical and recreational consumers. But remember, to purchase medical cannabis, you will need a Massachusetts Cannabis card and your ID. And if you’re purchasing medical cannabis for a patient, you must be registered as a caregiver with the Massachusetts Department of Public Health.

If you'd like to become a patient at Panacea Wellness, you can visit us at our dispensary at 29 Harding Street in Middleborough, or you can register through our online form.

At Panacea, we're here for you and all your cannabis questions. Stop by our shop in Middleborough anytime from 10AM - 8PM, Monday - Saturday, and from 12PM - 7PM on Sunday. You can also pre-order your favorite cannabis products online and use our discreet delivery option.