Updated: Mar 21
A 2020 study entitled "Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors" that was published in the journal Frontiers in Pharmacology investigated the issue of a possible ensemble, or entourage, effect caused by the synergistic interaction of cannabinoids and terpenes within the human endocannabinoid system (ECS).
The study observed that much interest has developed for the entourage effect theory, which has "provoked research into the activity of minor chemical constituents of the [cannabis] plant—including volatile [terpenes] such as myrcene, α-pinene and β- pinene, β-caryophyllene [BCP], and limonene." It also noted that, to date, "no clear interaction has been identified" in terms of proof of a theoretical entourage effect.
This study had the goal of determining "whether terpenes in the cannabis plant have detectable receptor-mediated activity, or modify the activity of Δ9-THC, CBD, or the endocannabinoid 2-AG at the cannabinoid receptors [CB1 and CB2]."
Brief Cannabinoid Discovery History
The study's introduction provides a short history lesson, noting that the first cannabinoid for which the molecular chemical structure was determined was cannabinol (CBN) in 1933.
American chemist Roger Adams
In 1940, celebrated American chemist Roger Adams isolated and identified the molecular structure of cannabidiol (CBD). Although tetrahydrocannabinol (THC) was isolated from the plant by a group in 1942, the complete chemical structure of this popular cannabinoid was not determined until the mid-1960s by pioneering cannabinoid researcher Raphael Mechoulam in Israel (due to the emergence of modern testing equipment, most notably gas chromatography, an innovation that did not occur until 1952).
"The report noted that the 'entourage effect' theory was first proposed and coined by a team of Israeli scientists in 1998."
"In the years since, at least 489 different compounds...have been identified from cannabis," reported the study in an illustration of the complexity of the plant's literal pharmacopeia of phytomolecules. Among these, cannabinoids, flavonoids, and terpenes are the major families that have proven positive efficacy in a range of thousands of peer-reviewed research studies.
The report noted that the "entourage effect" theory was first proposed and coined by a team of Israeli scientists in 1998. "Since the publication of the  study, the term 'entourage effect' has been co-opted to refer to the idea that whole cannabis possesses greater therapeutic potential than its individual components, with many websites suggesting that terpenes can modify the high produced by Δ9-THC."
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The study's authors reported that two separate studies from 2019 explored the topic of a potential entourage effect produced by the interaction of cannabinoids and terpenes, with both revealing no hard evidence for such a mechanism.
Five Terpenes Examined
The study examined the biochemical activities of five terpenes for any evidence of entourage effect activity:
The study found that "none of the terpenes tested significantly altered the binding of [cannabinoids with] CB1 [receptors in the ECS]. The scientists found the same lack of binding affinity on the part of the terpenes for CB2 receptors—with the exception of BCP, which displayed weak binding.
"None of the terpenes tested significantly altered the binding of [cannabinoids with] CB1 [receptors in the ECS]," reported the study's authors.
The researchers concluded that their study data "do not support the idea that any of the five terpenes tested...contribute to a putative entourage effect directly through the cannabinoid receptors [CB1 and CB2]."
While the study reiterated that "β-Caryophyllene was found to bind weakly to CB2," it summarized by stating that "no other functional or binding effects were detected for the terpenes alone or in combination with CBD, [the endocannabinoid] 2-AG, or Δ9-THC."
Visit the original study.
But Wait, There's More
Students and readers who are fans of terpenes or the entourage effect may, understandably, be a bit saddened by the results of this study. However, that's not the end of the story.
In April 2021, a group of researchers for the first time uncovered proof of the interaction of terpenes with the CB1 receptor of the endocannabinoid system. Read the Higher Learning LV study summary here: How Terpenes & Cannabinoids Work Together.
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