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The Entourage Effect: Is it Real?

The “entourage effect” occurs when natural components within a plant interact together to produce strong effects within the human body. It is a synergistic effect, or “an effect arising between two or more agents, entities, factors, or substances that produces an effect greater than the sum of their individual effects.”

If multiple compounds in their natural state are combined, the effects are often multiplied. The different compounds can amplify each other’s effects, making the plant more effective in treating unwanted medical symptoms. Several studies support the entourage effect, including a 2015 study from the Journal of Pharmacology and Pharmacy, that stated that “It is likely that other components in the (Cannabis) extract synergize with CBD to achieve the desired anti‐inflammatory action.”

Natural and alternative medicine commonly uses entire plants for medical purposes. This typically makes the remedy more powerful than just isolating part of the plant. This is referred to as whole plant medicine, where herbalists excel at matching holistic, plant-based treatments to a variety of ailments. In this case, treatment may be more effective in plant form than in pills due to mounting evidence that suggests medical substances are more useful as plant-based treatments.

The CBD-THC Tag Team: Entourage Effect at Work

Cannabis contains many more active compounds than THC alone. A number of cannabinoids have been found to work in conjunction with THC to enhance symptom relief. Cannabidiol (CBD), the major cannabinoid that contains no psychoactive effects, has potential to modulate the psychoactive effects of THC.

An example of the Entourage Effect was witnessed in the mid 1980s with the drug “Marinol,” a popular form of synthetic THC. Medical professionals expected this drug to work just as well as it would if it consisted of whole plant medication. However, Marinol contained only one cannabinoid, and it was soon realized that patients preferred to use whole plant medication.

Hemp is different from cannabis, and contains far more CBD than THC. Although THC content in CBD is low, cannabis can be specially grown to produce equal levels in both of the cannabinoids. This translates into some of the most effective treatments around. The ratio of THC to CBD plays an exceptional role in determining the efficacy of the cannabis plant and its therapeutic applications.

The entourage effect can be produced by a myriad of mechanisms and activities. Each of these mechanisms falls into one of three categories: (1) Pharmacokinetic Interaction, (2) Direct Pharmacodynamic Interaction, and (3) Indirect Pharmacodynamic Interaction.
Here is a look at how these mechanisms work in the CBD-THC tag team’s favor:

Pharmacokinetic Interaction

Pharmacokinetic activities of the entourage effect include the absorption, distribution, metabolism and elimination of chemical compounds within the body. There are instances where one compound can interfere with another compound’s pharmacokinetic processes. For example, research has found CBD to possess the ability to inhibit the CYP2C9 enzyme, one of the main enzymes for metabolizing THC. By doing so, CBD can reduce the intensity and duration of the psychoactive effects of THC.

Direct Pharmacodynamic Interaction

A direct pharmacodynamic interaction occurs when two compounds from the cannabis plant are simultaneously interacting at the same receptor. This comes in three different forms: (1) Antagonistic Interaction, (2) Additive Interaction, (3) Synergistic Interaction.

  • Antagonistic Interaction
    • In an antagonistic interaction, one compound inhibits the effects of another compound. For example, CBD acts as an antagonist to turn down the activation of the CB1 receptor by THC. Other than this receptor, CBD also blocks THC activities at the CB2 receptor and GPR55 receptor.
  • Additive Interaction:
    • CBD and THC can focus their functions towards specific targets in the body. When this occurs, the compounds typically have the same level of potency at the target, even if they are ingested at different dosages. Interestingly, this means that 10 mg of CBD can have the same effect as 5 mg as THC.
  • Synergistic Interaction:
    • A synergistic interaction produces a greater than additive effect when two compounds combine. According to a study, CBD can prolong the therapeutic effects of THC by slowing down its breakdown process in the liver.

Indirect Pharmacodynamic Interaction

An indirect pharmacodynamic interaction refers to the interaction between two cannabis compounds through two different receptors. It enables CBD to modulate some specific effects of THC in a particular neurotransmitter system. For example, CBD could potentially inhibit the anxiety producing effects of THC through the serotonin system.

CBD & Terpenes

CBD-Terpene team can improve/enhance the treatment of inflammation, pain and other ailments through a different approach. Terpenes are similar to CBD and have their own healing capabilities. The combination of CBD and terpenes create an entourage effect, enhancing the healing properties provided by CBD.

Terpenes are the essential oils found in the trichomes of the cannabis plant and give all plants, flowers and herbs their diverse aromas. Research has shown that terpenes can enhance the health effects of CBD. When CBD and terpenes combine, these two compounds can produce synergy for improving treatment of inflammation, bacterial infection, pain, anxiety, depression, epilepsy, and other conditions. Researchers have discovered that a terpene called “myrcene” can loosen the blood-brain barrier in order to facilitate easy absorption of CBD. In addition to this, the terpenes “linalool” and “limonene” are known to work with CBD to fight acne. Another honorable mention is the terpene “pinene,” that helps CBD reduce the psychoactive effects of cannabis.

Food For Thought on the Entourage Effect

If using the entire plant (or plant extract), is more effective than using lab-produced drugs, why aren’t we using the whole-plant-as-medicine more often?

Unfortunately, many obstacles stand in the way of a “whole plant medicine” approach. The three main reasons for this restriction are:

  1. The quality control of plants is poor, resulting in potentially contaminated, adulterated, less effective or even unsafe herb products. The Food and Drug Administration (FDA) does not closely monitor herbal medicine products the same way it does for medical products.
  2. The potency of botanical extracts is inconsistent because the environment and weather affect each year’s crop of plants, causing uncertain circumstances for production.
  3. Botanical products are not standardized due to insufficient knowledge and understanding of the many components that contribute to the therapeutic effects from cannabis plants.

Ongoing research should shed more light on whole plant medicine, enabling consumers and medical professionals to harness the true medicinal power of the plant in its entirety.


  • The “entourage effect” refers to compounds working together to create the most powerful effects a cannabis plant can produce.
  • The ratio of THC to CBD plays an important role in determining the efficacy of the cannabis plant.
  • Whole-plant CBD may be more effective than CBD on its own.
  • The combination of terpenes and CBD enhance the positive effects of CBD.

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