Entourage effect explained

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]

Compounds

Cannabidiol

Vaped or smoked cannabidiol (CBD), primarily between 250°C to 300°C, may be converted into THC.[3] Cannabis strains with relatively high CBD:THC ratios have unknown effects on anxiety.[4]

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.[5] [6]

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.

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.[9] [10]

Background

The phrase entourage effect was introduced in 1999.[11] [12] 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.[13] 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.[12]

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.[14] The review concluded that the term, "entourage effect", is unfounded and used mainly for marketing.[14]

Notes and References

  1. Grof CP . Cannabis, from plant to pill . British Journal of Clinical Pharmacology . 84 . 11 . 2463–2467 . November 2018 . 29701252 . 6177712 . 10.1111/bcp.13618 .
  2. Russo EB . Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects . British Journal of Pharmacology . 163 . 7 . 1344–64 . August 2011 . 21749363 . 3165946 . 10.1111/j.1476-5381.2011.01238.x .
  3. Czégény . Z . Nagy . G . Babinszki . B . Bajtel . Á . Sebestyén . Z . Kiss . T . Csupor-Löffler . B . Tóth . B . Csupor . D . CBD, a precursor of THC in e-cigarettes. . Scientific Reports . 26 April 2021 . 11 . 1 . 8951 . 10.1038/s41598-021-88389-z . 33903673 . 8076212. 2021NatSR..11.8951C .
  4. Book: Russo EB, Tyler VM . Handbook of Psychotropic Herbs: A Scientific Analysis of Herbal Remedies for Psychiatric Conditions. 22 December 2015. Routledge. 978-1-136-38607-7. 233–.
  5. Web site: Some of the Parts: Is Marijuana's "Entourage Effect" Scientifically Valid?. Chen A . Scientific American. 2017-12-31 . 20 April 2017.
  6. LaVigne . Justin E. . Hecksel . Ryan . Keresztes . Attila . Streicher . John M. . Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity . Scientific Reports. 11. 8232. en . 10.1038/s41598-021-87740-8 . 15 April 2021. free . 8050080 .
  7. Karl W. Hillig . Paul G. Mahlberg . 2004 . A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae) . . 91 . 6 . 966–975 . 21653452 . 10.3732/ajb.91.6.966. free .
  8. Niesink RJ, Rigter S, Koeter MW, Brunt TM . Potency trends of Δ9-tetrahydrocannabinol, cannabidiol and cannabinol in cannabis in the Netherlands: 2005-15 . Addiction . 110 . 12 . 1941–50 . 2015 . 10.1111/add.13082 . 26234170.
  9. 10.1371/journal.pone.0267498. 1932-6203. 17. 5. –0267498. Smith. Christiana J.. Vergara. Daniela. Keegan. Brian. Jikomes. Nick. The phytochemical diversity of commercial Cannabis in the United States. PLOS ONE. 2022. 35588111. 9119530. 2022PLoSO..1767498S. free.
  10. 1664-462X. 13. Murovec. Jana. Eržen. Jan Jurij. Flajšman. Marko. Vodnik. Dominik. 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. 2022. 786161. 10.3389/fpls.2022.786161. 35283868. 8907982. free.
  11. Ben-Shabat S, Fride E, Sheskin T, Tamiri T, Rhee MH, Vogel Z, Bisogno T, De Petrocellis L, Di Marzo V, Mechoulam R . 6 . An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity . European Journal of Pharmacology . 353 . 1 . 23–31 . July 1998 . 9721036 . 10.1016/s0014-2999(98)00392-6 .
  12. News: Medical marijuana and "the entourage effect" . Gupta S . CNN . 31 December 2017 . 11 March 2014 .
  13. Russo EB . The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No "Strain," No Gain . Frontiers in Plant Science . 9 . 1969 . 2019-01-09 . 30687364 . 6334252 . 10.3389/fpls.2018.01969 . free .
  14. Cogan PS . 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 . August 2020 . 32116073 . 10.1080/17512433.2020.1721281 . 211726166 . PS .

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