The entourage effect is a proposed mechanism by which cannabis compounds other than tetrahydrocannabinol (THC) act synergistically with it to modulate the overall psychoactive effects of the plant. Cannabidiol (CBD) is under preliminary research for its potential to modify the effects of THC, possibly mitigating some of the negative, psychosis-like effects of THC. There are numerous terpenes present in the cannabis plant and variation between strains. Some of the different terpenes have known pharmacological effects and have been studied.
The phrase entourage effect was introduced in 1999. While originally identified as a novel method of endocannabinoid regulation by which multiple endogenous chemical species display a cooperative effect in eliciting a cellular response, the term has evolved to describe the polypharmacy effects of combined cannabis phytochemicals or whole plant extracts. The phrase now commonly refers to the compounds present in cannabis supposedly working in concert to create “the sum of all the parts that leads to the magic or power of cannabis”. Other cannabinoids, terpenoids, and flavonoids may be part of an entourage effect. The entourage effect is considered a possible cannabinoid system modulator and is achieved in pain management.
Endogenous 2-acyl-glycerols can increase 2-arachidonoylglycerol biological activity, which alone shows no significant activity. This entourage effect may represent a novel endogenous cannabinoid activity molecular regulation route. Cannabinoid system modulators like N-palmitoylethanolamine may exhibit the entourage effect, increasing receptor affinity to enhance endogenous anandamide activity and/or reducing enzymatic anandamide degradation.
One study found that none of the six most common terpenoids in Cannabis directly activated CB1 or CB2, or modulated the signalling of the phytocannabinoid agonist Δ9-THC. The study focused on whether the terpenes had activity at the CB receptor but did not identify other receptors ( non CB-receptors) whose function may be altered by the terpenes, causing indirect modulation of the CB-receptors.
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