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.
A 2020 review of research found no entourage effect in most studies, while other reports claimed mixed results, including the possibility of increased adverse effects. The review concluded that the term, "entourage effect", is unfounded and used mainly for marketing.
- Grof, Christopher P. L. (24 May 2018). "Cannabis, from plant to pill". British Journal of Clinical Pharmacology. 84 (11): 2463–2467. doi:10.1111/bcp.13618. ISSN 0306-5251. PMC 6177712. PMID 29701252.
- Russo EB (August 2011). "Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects". British Journal of Pharmacology. 163 (7): 1344–64. doi:10.1111/j.1476-5381.2011.01238.x. PMC 3165946. PMID 21749363.
- "Cannabis study reveals how CBD offsets the psychiatric side-effects of THC". ScienceDaily. Retrieved 2020-01-22.
- Chen A (20 April 2017). "Some of the Parts: Is Marijuana's "Entourage Effect" Scientifically Valid?". Scientific American. Retrieved 2017-12-31.
- Fine PG, Rosenfeld MJ (2013-10-29). "The endocannabinoid system, cannabinoids, and pain". Rambam Maimonides Medical Journal. 4 (4): e0022. doi:10.5041/RMMJ.10129. PMC 3820295. PMID 24228165.
- Russo, Ethan B (2011). "Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects". British Journal of Pharmacology. 163 (7): 1344–1364. doi:10.1111/j.1476-5381.2011.01238.x. PMC 3165946. PMID 21749363.
- Ben-Shabat, Shimon; Fride, Ester; Sheskin, Tzviel; Tamiri, Tsippy; Rhee, Man-Hee; Vogel, Zvi; Bisogno, Tiziana; De Petrocellis, Luciano; Di Marzo, Vincenzo; Mechoulam, Raphael (July 1998). "An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity". European Journal of Pharmacology. 353 (1): 23–31. doi:10.1016/s0014-2999(98)00392-6. PMID 9721036.
- Gupta S (11 March 2014). "Medical marijuana and 'the entourage effect'". CNN. Retrieved 31 December 2017.
- Russo, Ethan B. (2019-01-09). "The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No "Strain," No Gain". Frontiers in Plant Science. 9: 1969. doi:10.3389/fpls.2018.01969. ISSN 1664-462X. PMC 6334252. PMID 30687364.
- Jerome, Bouaziz (April 1, 2017). "The Clinical Significance of Endocannabinoids in Endometriosis Pain Management". Cannabis and Cannabinoid Research. 2 (1): 72–80. doi:10.1089/can.2016.0035. PMC 5436335. PMID 28861506.
- Bouaziz, Jerome; Bar On, Alexandra; Seidman, Daniel S.; Soriano, David (January 2017). "The Clinical Significance of Endocannabinoids in Endometriosis Pain Management". Cannabis and Cannabinoid Research. 2 (1): 72–80. doi:10.1089/can.2016.0035. PMC 5436335. PMID 28861506.
- Cogan (2 March 2020). "The 'entourage effect' or 'hodge-podge hashish': the questionable rebranding, marketing, and expectations of cannabis polypharmacy". Expert Review of Clinical Pharmacology. 13 (8): 835–845. doi:10.1080/17512433.2020.1721281. PMID 32116073. S2CID 211726166.