Entourage effect

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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. [1] [2] The effect has also been applied in the case of psilocybin mushrooms, with other compounds besides psilocybin having been hypothesized to also contribute to the effects of the mushrooms. [3]

Contents

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. [4] [2] [5]

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.[ citation needed ] Both types are used as medical cannabis.

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. [8] [9]

Background

The phrase entourage effect was introduced in 1999. [10] [11] 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. [12] The phrase now commonly refers to the compounds present in cannabis purportedly working in concert to create "the sum of all the parts that leads to the magic or power of cannabis". [4] Other cannabinoids, terpenoids, and flavonoids may be part of an entourage effect. [11]

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. [13] The review concluded that the term, "entourage effect", is unfounded and used mainly for marketing. [13]

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. 1 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. ↑ Pepe M, Hesami M, de la Cerda KA, Perreault ML, Hsiang T, Jones AM (December 2023). "A journey with psychedelic mushrooms: From historical relevance to biology, cultivation, medicinal uses, biotechnology, and beyond". Biotechnol Adv. 69: 108247. doi:10.1016/j.biotechadv.2023.108247. PMID   37659744. Additionally, various compounds can collectively contribute to what is known as "the entourage effect", which describes the synergistic interaction of a variety of different metabolites that enhance the activity of the primary active components (Russo, 2019). Tryptamine concentrations and profiles across different Psilocybe species are highly variable. Thus, the diversity of Psilocybe species results in differential production of an assortment of tryptamines in different concentrations (Glatfelter et al., 2022), which is likely responsible for variable psychoactive effects of various mushrooms.
  4. 1 2 Chen A (20 April 2017). "Some of the Parts: Is Marijuana's "Entourage Effect" Scientifically Valid?". Scientific American. Retrieved 2017-12-31.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. 1 2 Gupta S (11 March 2014). "Medical marijuana and "the entourage effect"". CNN. Retrieved 31 December 2017.
  12. ↑ 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.
  13. 1 2 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.
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