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The entourage effect is a hypothesis that cannabis compounds other than tetrahydrocannabinol (THC) act synergistically with it to modulate the overall psychoactive effects of the plant.

Compounds

Terpenes

There are numerous terpenes present in the cannabis plant and variation in their contents between strains. Some terpenes are under preliminary research for their possible effects in vivo.

Hypothetical differences between C. indica and C. sativa

The effects of sativa may be used for a high, while indica may be used for its sedative effects. Both types are used as medical cannabis.

• Cannabinoid ratios: On average, Cannabis indica has higher levels of THC compared to CBD, whereas Cannabis sativa has lower levels of THC to CBD. However, huge variability exists within either species. A 2015 study shows the average THC content of the most popular herbal cannabis products in the Netherlands has decreased slightly since 2005.
• Terpene ratios: Sativa ancestry is associated with farnesene and bergamotene, while Indica ancestry is associated with myrcene, elemene, and sesquiterpene alcohols.

Criticism

In 2022, studies found that plants identified as "indica" or "sativa" based on common methods of differentiation (e.g. plant height or leaf shape) are not, in fact, chemically distinguishable, with many identified as "sativa" having cannabinoid ratios predicted of "indica" plants and vice versa. The authors have concluded that the chemical makeup of cannabis plants cannot be reliably determined by simple inspection of the plants' physical characteristics and that the "indica" and "sativa" labels are not informative as to the cannabinoids (or other chemical components) delivered.

Background

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.

Criticism

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.

References

1. Grof CP (November 2018). "Cannabis, from plant to pill". British Journal of Clinical Pharmacology. 84 (11): 2463–2467. doi:10.1111/bcp.13618. PMC 6177712. PMID 29701252.
2. ^ 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.
3. ^ Chen A (20 April 2017). "Some of the Parts: Is Marijuana's "Entourage Effect" Scientifically Valid?". Scientific American. Retrieved 2017-12-31.
4. LaVigne, Justin E.; Hecksel, Ryan; Keresztes, Attila; Streicher, John M. (15 April 2021). "Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity". Scientific Reports. 11 (1): 8232. doi:10.1038/s41598-021-87740-8. PMC 8050080. PMID 33859287.
5. Karl W. Hillig; Paul G. Mahlberg (2004). "A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae)". American Journal of Botany. 91 (6): 966–975. doi:10.3732/ajb.91.6.966. PMID 21653452.
6. Niesink RJ, Rigter S, Koeter MW, Brunt TM (2015). "Potency trends of Δ9-tetrahydrocannabinol, cannabidiol and cannabinol in cannabis in the Netherlands: 2005-15". Addiction. 110 (12): 1941–50. doi:10.1111/add.13082. PMID 26234170.
7. Smith, Christiana J.; Vergara, Daniela; Keegan, Brian; Jikomes, Nick (2022). "The phytochemical diversity of commercial Cannabis in the United States". PLOS ONE. 17 (5): –0267498. Bibcode:2022PLoSO..1767498S. doi:10.1371/journal.pone.0267498. ISSN 1932-6203. PMC 9119530. PMID 35588111.
8. Murovec, Jana; Eržen, Jan Jurij; Flajšman, Marko; Vodnik, Dominik (2022). "Analysis of Morphological Traits, Cannabinoid Profiles, THCAS Gene Sequences, and Photosynthesis in Wide and Narrow Leaflet High-Cannabidiol Breeding Populations of Medical Cannabis". Frontiers in Plant Science. 13: 786161. doi:10.3389/fpls.2022.786161. ISSN 1664-462X. PMC 8907982. PMID 35283868.
9. Ben-Shabat S, Fride E, Sheskin T, Tamiri T, Rhee MH, Vogel Z, et al. (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.
10. ^ Gupta S (11 March 2014). "Medical marijuana and "the entourage effect"". CNN. Retrieved 31 December 2017.
11. Russo EB (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. PMC 6334252. PMID 30687364.
12. ^ Cogan PS (August 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.

• Cannabinoids
• Cannabis and health
• Hypotheses