Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors
The two most abundant cannabinoids in cannabis are tetrahydrocannabinol (THC) and cannabidiol (CBD), both of which have known therapeutic effects in pain relief and immune regulation; however, only the former, THC, is responsible for the intoxicating effects that cannabis is most commonly known and used for. This is because THC binds to and activates both the type 1 cannabinoid receptors (CB1) in the nervous system and the type 2 cannabinoid receptors (CB2) in the immune system. In contrast, CBD only interacts with CB2. Therefore, CBD has received attention as a promising analgesic with low side effects.
The entourage effect is a proposed mechanism by which components in cannabis other than cannabinoids act synergistically with them to modulate the overall effects of the plant. Not only does this mean other components of cannabis can enhance the “high” sensations created by THC, but it also implies that whole cannabis possesses greater therapeutic potential than its individual components, as suggested by its proponents.
Minor chemical constituents of cannabis proposed to contribute to such entourage effects are volatile terpenoids including myrcene, alpha- and beta-pinene, beta-caryophyllene, and limonene. However, recent research has demonstrated that none of the above terpenoids interact with the cannabinoid receptors. Scientists have also found no evidence that terpenoids’ mediate the cannabinoids’ downstream psychoactive, analgesic or inflammatory effects. While these findings rule out direct interactions between terpenoids and cannabinoid receptors as the mechanism for entourage effects of terpenoids, they don’t rule out the existence of the entourage effect itself. More studies are already underway to further elucidate the biological mechanisms of this interesting effect.