The Entourage Effect: Why THC and CBD Are Better Together

The Entourage Effect: Why THC and CBD Are Better Together

Posted by Lily Kiepke on Oct 22nd 2020

Like any consumer, you want to make sure you’re getting the most out of your products.

That’s why if you’re using CBD, or any other cannabis product, you need to know about the entourage effect and how it can work for you.

Imagine if there was a way to target more areas of your body for relief, absorb more active ingredients, prevent bacteria from becoming resistant to treatment, and minimize nasty side effects all at once.

The entourage effect is capable of just that, and more.

As research continues to explode in the cannabis industry, evidence consistently supports the phenomenon known as the entourage effect.

In the end, some things are just better together.

Different Components of Cannabis

The cannabis plant contains many different chemical components, including cannabinoids, terpenes, terpenoids, and flavonoids.

In addition to these components, the cannabis plant also has “amino acids, proteins, sugars, enzymes, fatty acids, esters” and other chemical compounds, adds Dr. Malik Burnett of Medical Jane, a prominent resource for medical marijuana patients.

When all of these ingredients are taken together, they work in collaboration to provide powerful therapeutic relief through a theory known as the “entourage effect.”


Cannabinoids are defined as the “major active chemical ingredients of the cannabis plant” by Visual Capitalist, a leading source for data-driven infographics. Cannabinoids found in the cannabis plant are also referred to as phytocannabinoids.

Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most well-known and widely researched cannabinoids. THC can be used to relieve pain and nausea, as a sleep aid, and as an appetite and mood stimulant. CBD has additional anti-inflammatory and anti-anxiety effects, as well as the ability to reduce seizures.

Other cannabinoids include cannabichromene (CBC), cannabigerol (CBG), and cannabinol (CBN), which have “similar therapeutic properties” according to Visual Capitalist.

Cannabinoids bind to different receptors of the body-wide signaling system known as the endocannabinoid system (ECS). Discovered in the late 90’s, the ECS consists of cannabinoid receptors, endocannabinoids (cannabinoids naturally produced by the body), and enzymes that break down substances after they have served their purpose.

Medical Jane uses a “key and lock” metaphor to describe the relationship between cannabinoids, endocannabinoids, and cannabinoid receptors; cannabinoids and endocannabinoids are the “keys” that “unlock” cannabinoid receptors on the surface of cells when they bind to them.

Cannabinoids can be described as either “agonists” or “antagonists” depending on their behavior when they bind to cannabinoid receptors.

If the receptor responds to the cannabinoid “the same way as it would to a naturally occurring hormone or neurotransmitter,” it is known as an agonist, asserts Medical Jane.

In contrast, if a cannabinoid “prevents the receptor from binding to the naturally occurring compound, thereby causing the resulting event (e.g. pain, appetite, alertness) to be altered or diminished,” it is classified as an antagonist, states Medical Jane.

Depending on whether a cannabinoid is an agonist or an antagonist, it can either enhance positive effects or block negative ones.

Terpenes, Terpenoids, and Flavonoids

Visual Capitalist defines terpenes as “organic, aromatic compounds found in the oils of all flowers, including cannabis.”

Terpenes are responsible for the distinct smell and flavor of cannabis. Some examples of terpenes include myrcene, pinene, and limonene; each have their own distinct smell and can be found in other plants such as lemongrass, pine needles, and peppermint.

Terpenes have their own “potential medical value,” such as relieving pain or enhancing sleep, notes Visual Capitalist. Additionally, Medical Jane details how terpenes can have similar effects to antidepressant medications like Prozac and Elavil by acting as serotonin uptake inhibitors and enhancing or increasing norepinephrine and dopamine activity.

Medical Jane also clarifies the difference between terpenes and terpenoids, informing readers “the main difference between terpenes and terpenoids is that terpenes are hydrocarbons (meaning the only elements present are carbon and hydrogen); whereas terpenoids have been denatured by oxidation (drying and curing the flowers) or chemically modified.”

Similarly to terpenes, flavonoids also occur naturally in many fruits, vegetables, and other plants and plant products. Flavonoids are nutrient compounds found in plants known as phytonutrients.

Medical Jane explains the impact and importance of flavonoids, stating “flavonoids are known for their antioxidant and anti-inflammatory benefits, as well as their contribution of vibrant color to many of the foods we eat,” with the blue in blueberries or red in raspberries given as examples.

Of the 6,000 flavonoids known to scientists, “about 20 of these compounds [...] have been identified in the cannabis plant,” says Medical Jane. The potential therapeutic effects of flavonoids are still being explored by researchers, but clinical findings thus far have been promising.

The Difference Between THC and CBD

THC and CBD have the exact same chemical structure, including 21 carbon atoms, 30 hydrogen atoms, and 2 oxygen atoms.

However, the cannabis research resource Loud Cloud Health reveals “what sets them apart is a slight difference in how the atoms are arranged, which accounts for the different effects on your body.” The arrangement of CBD does not allow it to bond with the body’s CB1 receptors directly. In fact, CBD may even neutralize the “high” induced by THC.

THC, on the other hand, can bind directly to CB1 receptors, which are highly concentrated in the brain. “This is the reason why THC has psychoactive effects on the brain,” explains Loud Cloud Health.

The Entourage Effect

The entourage effect is the theory that cannabis compounds work better together than in isolation. The theory is based on the synergy between the chemical compounds, or the idea that the combined effect is greater than the sum of their separate effects.

The term was first coined in 1998 by Israeli scientists Shimon Ben-Shabat and Raphael Mechoulum, who extensively researched the endocannabinoid system throughout the early to mid-90s.

In his article “The Entourage Effect: Whole-Plant Cannabis Medicine,” Dr. Burnett details how the entourage effect was later expanded upon in 2009 by researchers Wagner and Ulrich-Merzenich, who defined the four ways whole-plant products are more beneficial:

  1. Ability to affect multiple targets within the body
  2. Ability to improve the absorption of active ingredients
  3. Ability to overcome bacterial defense mechanisms
  4. Ability to minimize adverse side effects

In a 2003 study on whether or not THC is necessary to receive all the benefits of cannabis, researchers found the whole-plant extract to have “significantly more antispastic effect” than THC alone when used in a mouse model of multiple sclerosis (MS), cites Dr. Burnett. Researchers credited the difference to the presence of CBD, which can increase activity within the endocannabinoid system.

Additionally, when terpenes and terpenoids are present, cannabinoids can be more easily and extensively absorbed by the body.

While cannabinoids themselves are antibacterial, Dr. Burnett reveals “whole-plant cannabis extracts have non-cannabinoid constituents which also have antibacterial properties.” These additional cannabis components are valuable in preventing the development of resistant bacteria. This is beneficial as bacteria can evolve over time to become resistant to antibiotics or other forms of treatment.

The entourage effect is also said to minimize negative side effects of individual cannabinoids. For example, some users of THC report feelings of anxiety or paranoia—these effects are minimized when THC is taken in conjunction with CBD, likely due to CBD acting as an antagonist on CB1 receptors.

Research on the Entourage Effect

Author and health outcomes expert Sarah Ratliff at Cannabis Tech, a media company devoted to the cannabis market, guides readers through existing cannabis research on the entourage effect.

Ratliff describes a 2010 randomized controlled clinical trial in which patients received the pain relieving drug Sativex, which contains a balance of THC and CBD. Cancer patients experiencing pain were given either Sativex, an identical amount of pure THC, or a placebo.

“Sativex was found to offer a significant pain-killing effect in 40 percent of the patients who took it, which made it twice as potent as the THC extract,” reveals Ratliff. The increased impact on pain reduction is attributed to CBD, likely due to its own interactions with the endocannabinoid system.

Later, in 2010, a study explored the differences in experiences of those who smoked solely THC, and those who used cannabis containing both THC and CBD. Ratliff explains how “those who consumed pure THC experienced memory problems and other cognitive difficulties (typically associated with that compound), [while] those who smoked THC and CBD together experienced no such troubles.” 

While research has mostly focused on the interactions between THC and CBD, the true therapeutic potential of the terpenes, terpenoids, and flavonoids present in cannabis is still being explored.

Ratliff recalls a 2018meta-analysis which proved “CBD extracts were far less effective in reducing the occurrence of seizures in epilepsy patients than extracts that included a mixture of cannabis cannabinoids, including terpenes.” In fact, 71% of patients who took the mixture experienced improvements, whereas only 46% of those who took pure CBD reported the same result, the study concluded.

How to Achieve the Entourage Effect

Experiencing the entourage effect firsthand is simple and easy with full spectrum CBD.

Full spectrum CBD contains all of the beneficial cannabinoids, terpenes, terpenoids, and flavonoids that drive the entourage effect. Full spectrum CBD differs from broad spectrum CBD in that it still contains a THC content of up to 0.3%, as per legal regulations.

Enjoy the amplified health benefits quickly and conveniently with the convenience of a dropper. As with other tinctures, full spectrum CBD can be taken sublingually (under the tongue) for fastest results, or added to any food or beverage.

Already use THC or THC-infused products? Check out PHD Organic’s extensive line of third-party lab tested CBD products to alleviate adverse side effects caused by THC alone.

Let’s Review

The cannabis plant is made up of cannabinoids, terpenes, terpenoids, and flavonoids, among other substances.

Cannabinoids, such as THC and CBD, are active ingredients in cannabis that bind with cannabinoid receptors. A cannabinoid that interacts with a receptor naturally is known as an agonist, whereas, if a cannabinoid blocks a receptor’s response, it’s classified as an antagonist.

Terpenes are the compounds that produce the smell and flavor associated with cannabis, and have their own therapeutic potential similar to antidepressants. A terpene that has been dried, cured, or chemically modified is called a terpenoid. A flavonoid is a phytonutrient, or a nutrient found in plants, with additional anti-inflammatory and antioxidant benefits.

While CBD and THC have the same chemical structure, CBD is arranged in a way that does not bind directly with the CB1 receptor, and therefore does not affect the brain.

The entourage effect theorizes whole-plant products are more powerful due to the synergy between the chemical compounds. When taken together, there is an increased ability to affect more of the body, absorb more of the active ingredients, fight the development of resistant bacteria, and curtail adverse side effects.

Research supports the entourage effect, although mostly focusing on the benefits of taking CBD in conjunction with THC, which can reduce pain, paranoia, and anxiety.

Achieving the entourage effect is easy with an all-in-one product like full spectrum CBD.

Check Back for PHD Organic’s Latest Product: Full Spectrum CBD Available in Tinctures!


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About the Author

Lily Kiepke is a freelance writer and blogger based in the Denver metropolitan area. She enjoys using CBD to relieve anxiety and improve sleep. When she is not writing about cannabis, she can be found hiking in the Rocky Mountains or curled up with a good true crime book.