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Terpenes & THC Activate the ECS Study
A June 2023 study entitled "Selected Cannabis Terpenes Synergize with THC to Produce Increased CB1 Receptor Activation" that was published in the peer-reviewed journal Biochemical Pharmacology explored the ways in which some cannabis-derived terpenes interact with delta-9 tetrahydrocannabinol (THC) to increase the activation of CB1 receptors in the human endocannabinoid system (ECS).
"In the current study we used a controlled in-vitro heterologous expression system to quantify the activation of CB1 receptors by sixteen cannabis terpenes individually, by THC alone, and by THC-terpenes mixtures," stated the researchers.
"In the current study we examined the activation of CB1 receptors by sixteen cannabis terpenes individually, by THC alone, and by THC-terpenes mixtures."
The study described cannabis as a "multifaceted plant containing hundreds of different chemical compounds" and that these include cannabinoids, terpenes, and flavonoids (among many others). It noted that a continually growing body of evidence and research employs terms such as "full spectrum" and "whole plant," "suggesting that combinations of cannabis plant components—more specifically, compositions of selected chemovars—provide better treatment results compared to results of isolated cannabinoids."
"To the best of our knowledge, this is the first demonstration of THC-terpene synergism in an in vitro controlled setting. Importantly, synergism here is found at terpene/THC ratios similar to those in the cannabis plant," reported the research.
Sixteen Terpenes Studied
Terpenes & THC Activate the ECS. Sixteen cannabis terpenes were studied, including the following monoterpenes (the most common class of terpene that features two isoprene units):
Beta-pinene
Sabinene
And the following monoterpenoids (oxygen-containing monoterpenes):
And the following sesquiterpenes (three isoprene units):
And the following sesquiterpenoids (oxygen-containing sesquiterpenes):
Terpenes & THC Activate the ECS Results
Terpenes & THC Activate the ECS. Overall, the researchers found that terpenes activated CB1 receptors in the ECS. Moreso, they observed that this ECS activation was enhanced (often, significantly) by the addition of THC. "CB1-dependent activations were demonstrated upon application of twelve cannabis terpenes tested; activation degrees ranged between 10-50 percent of the activation obtained using similar THC concentrations," reported the study.
"The terpenes that most enhanced CB1 activation when combined with THC included beta-pinene, borneol, geraniol, limonene, linalool, ocimene, sabinene, and terpineol."
The terpenes that most enhanced CB1 activation when combined with THC included beta-pinene, borneol, geraniol, limonene, linalool, ocimene, sabinene, and terpineol. The scientists noted that this was true even at relatively low doses of terpenes that reflect those found naturally in the plant.
The terpenes that least enhanced CB1 activation, displaying limited activity, included alpha-pinene (α-pinene), myrcene, and BCP (β-caryophyllene).
Terpenes & THC: Entourage Effect?
The study's authors reported that the term "entourage effect" was coined by Ben-Shabat, an Israeli researcher, to "describe cases wherein co-existence of a compound having no ECS activity on its own, result in an increased ECS activation by a cannabinoid." They reported that not only do terpenes and THC feature a synergistic relationship within the ECS that could be labeled an entourage effect, but that this bond goes "beyond the classical definition of entourage."
Terpenes & THC Activate the ECS Conclusions
Terpenes & THC Activate the ECS. The scientists concluded that terpenes enhance the activation of the CB1 ECS receptor, sometimes significantly (to the point that it exceeds the common definition of entourage effect). The conclusions section of the study is featured below:
"While the term 'entourage' might not fit here, this study demonstrates synergism in selected terpene-THC systems."
"In the current study, we demonstrated terpene-derived CB1 receptor activation and terpene-derived amplification of THC activity at CB1 receptor by a subset of cannabis terpenes. Importantly, for some of those terpenes, a major amplification exists already at terpene to THC ratios similar to those in the cannabis plant, and at terpene concentrations as low as 0.001–0.01 µM.
"While the term 'entourage' might not fit here, this study demonstrates synergism in selected terpene-THC systems, indicating terpene-induced modulation of THC-CB1 receptor interactions. This finding motivates searching for such synergism in other receptor-cannabinoid-terpene systems as well.
"The notable CB1 receptors activation and the desired synergism with THC were shown by only a fraction of the cannabis terpenes, many of which are not the most common ones. Thus, reaching 'whole plant' or 'full spectrum' composition is not necessarily an advantage.
"For enhanced therapeutic effects, medical cannabis should be rich in the terpenes most suitable for activation of receptors involved with the specific indication to be treated."
"For enhanced therapeutic effects, medical cannabis should be rich in the terpenes most suitable for activation of receptors involved with the specific indication to be treated. Developing genetics rich in selected terpenes is doable, but requires major efforts and time. Enrichment of cannabis extracts with selected terpenes, sourced from cannabis or from other plants, is much easier and applicable to tablets and capsules produced from such extracts.
"The use of selected terpenes may enable reducing the THC dose in some treatments, and as a result, potentially minimizing the THC-related adverse effects. This would also help in adjusting the treatment to more sensitive populations such as children and elderly. Enrichment with selected terpenes may allow for composition adjustment to personal needs and to changes during chronic use, such as for daytime versus for sleep."
View the original study.
Also see our related article Study: Terpenes & Entourage Effect.
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