The entourage effect is a proposed mechanism by which compounds present in cannabis which are largely non-psychoactive by themselves modulate the overall psychoactive effects of the plant (these resulting principally from the action of the main psychoactive component of cannabis, tetrahydrocannabinol (THC).
Cannabidiol (CBD) is believed to be the major modulatory component of cannabis, mitigating some of the negative, psychosis-like effects of THC, and is included in some medicinal formulations alongside THC. CBD co-administration also reduces the negative effects of THC on memory. Myrcene, which is recognized as a sedative component in hops, may be responsible for the sedative effects ("couch lock") of certain cannabis strains (sedative effects are commonly ascribed to the indica cannabis type). Linalool may also contribute to the entourage effect, modulating the glutamate and GABA neurotransmitter systems to produce sedative and anxiolytic effects.
Though the idea of the entourage effect has taken root in the cannabis industry and among consumers, the concept is often based on conjecture and anecdotal evidence as rigorous scientific underpinning is lacking.
The phrase entourage effect was introduced in 1998 by S. Ben-Shabat, and by Raphael Mechoulam, to represent a novel endogenous cannabinoid molecular regulation route. The phrase 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”, according to Chris Emerson. Other cannabinoids', terpenoids', and flavonoids' contribution to clinical cannabis effects has been espoused as an “entourage effect”.
The entourage effect is considered a cannabinoid system modulator and is achieved in pain management through increasing receptors affinity to enhance endogenous anandamide activity and/or reducing enzymatic anandamide degradation.
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 be said to exhibit the entourage effect, increasing receptors affinity to enhance endogenous anandamide activity and/or reducing enzymatic anandamide degradation.
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