2021 Study: How Terpenes & Cannabinoids Work Together

In April 2021, a research study entitled "Cannabis Sativa Terpenes are Cannabimimetic and Selectively Enhance Cannabinoid Activity" that was published in the journal Scientific Reports was released. It investigated the ways in which terpenes and cannabinoids interact.

Of note, the study referenced the controversial theory (or hypothesis) of how cannabinoids and terpenes may synergistically interact to reveal or amplify particular efficacies that is called the entourage effect. Because the study was performed using rodent subjects instead of humans, readers are warned to avoid jumping to conclusions and assuming major benefits for humans.

Of note, the study referenced the controversial theory of how cannabinoids and terpenes may synergistically interact to reveal or amplify particular efficacies that is called the entourage effect.

That said, rodents feature an endocannabinoid system (ECS) that is relatively similar to that of humans (the same can be said for dogs and cats). Studies of this type provide valuable data and insight into the mechanisms of phytomolecules such as cannabinoids and terpenes. Because the entourage effect is a theory, much data—both clinical studies involving human subjects and non-clinical investigations with petri dishes or animals—must be collected and analyzed prior to declaring health benefits in people.

Reported the study's authors, "Limited evidence has suggested that terpenes found in cannabis...are analgesic [pain reducing] and could produce an 'entourage effect' whereby they modulate cannabinoids to result in improved outcomes. However this hypothesis is controversial, with limited evidence."

The researchers found that, while many patient-activists and thought leaders tout the benefits of whole plant medicines that feature broad-spectrum or full-spectrum formulations, "the few studies performed to date have shown no interaction."

They reported that their study is the first to identify the cellular receptors (neurotransmitters) utilized by terpenes within the ECS—chiefly the CB1 and A2a receptors. When terpenes bind with these specialized microscopic receptors, the researchers found that they sometimes demonstrate cannabinoid-like (cannabimimetic) behavior.

"We found that the terpenes α-humulene, geraniol, linalool, and β-pinene produced cannabinoid...behaviors in mice, suggesting cannabimimetic activity."

"We found that the terpenes α-humulene, geraniol, linalool, and β-pinene produced cannabinoid...behaviors in mice, suggesting cannabimimetic activity."

The scientists reported that their study data and results suggest that "terpenes are cannabimimetic, inducing at least three out of four of the classic cannabinoid...behaviors."

They concluded that their data reveal that "cannabis terpenes are multifunctional cannabimimetic ligands that provide conceptual support for the entourage effect hypothesis and could be used to enhance the therapeutic properties of cannabinoids."