The Entourage effect
The Entourage effect

What is the Entourage effect?

The term ‘entourage effect’, first mentioned in 1999 [1], describes a phenomenon where the activity of the two main active endocannabinoids (anandamide and 2-Ara-Gl) is potentiated when biologically inactive endocannabinoids with similar structure are present. The idea that close-structured inactive substances potentiate the actions of active ones, intrigued scientists to investigate if the same goes for cannabinoids contained in cannabis (i.e. phytocannabinoids), as the plant contains approximately 120 cannabinoids and 445 non-cannabinoids (flavonoids, terpenes and other minor components), a rich profile of possible entourage substances [2]. 
Indeed, experiments have shown that in a lot of cases, cannabis extracts are more effective than single compounds contained in cannabis in alleviating inflammation, pain relief, and inhibition of cancer cells in vitro and in vivo. The best evidence of the superiority of cannabis extracts compared to pure substances is a meta-analysis of 11 epilepsy-related clinical studies involving 670 patients. The data showed that cannabis extracts high in CBD have almost the same therapeutic efficacy as 97% pure CBD but require only one fifth of the dose, indicating an entourage effect on epilepsy [3]. 
Note

Note: Although the entourage effect by definition, refers to the potentiation of the effect of an active substance with the help of some biologically inactive substances, the term nowadays is also used to describe a synergistic-polypharmacy effect of two or more active substances, such as (in the case of cannabis) Cannabidiol (CBD), Cannabinol (CBN), Cannabigerol (CBG), etc. 

Bibliography

1. Ben-Shabat S, Fride E, Sheskin T, et al: An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. European Journal of Pharmacology 353: 23-31, 1998. 

2. Mechoulam R and Ben-Shabat S: From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Natural prod- uct reports 16: 131-143, 1999. 

3. Russo EB: The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No “Strain,” No Gain. Frontiers in Plant Science 9: 2019.

Bibliography

1. Ben-Shabat S, Fride E, Sheskin T, et al: An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. European Journal of Pharmacology 353: 23-31, 1998. 

2. Mechoulam R and Ben-Shabat S: From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Natural prod- uct reports 16: 131-143, 1999. 

3. Russo EB: The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No “Strain,” No Gain. Frontiers in Plant Science 9: 2019.