entourage effect
{{Short description|Proposed mechanism of cannabis compounds}}
The entourage effect is a hypothesis that cannabis compounds, other than the cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD), act synergistically with cannabinoids to modulate the overall psychoactive effects of the plant.{{cite journal | vauthors = Grof CP | title = Cannabis, from plant to pill | journal = British Journal of Clinical Pharmacology | volume = 84 | issue = 11 | pages = 2463–2467 | date = November 2018 | pmid = 29701252 | pmc = 6177712 | doi = 10.1111/bcp.13618 }}{{cite journal | vauthors = Russo EB | title = Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects | journal = British Journal of Pharmacology | volume = 163 | issue = 7 | pages = 1344–64 | date = August 2011 | pmid = 21749363 | pmc = 3165946 | doi = 10.1111/j.1476-5381.2011.01238.x }} 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.{{cite journal | vauthors = Pepe M, Hesami M, de la Cerda KA, Perreault ML, Hsiang T, Jones AM | title = A journey with psychedelic mushrooms: From historical relevance to biology, cultivation, medicinal uses, biotechnology, and beyond | journal = Biotechnol Adv | volume = 69 | issue = | pages = 108247 | date = December 2023 | pmid = 37659744 | doi = 10.1016/j.biotechadv.2023.108247 | url = | quote = 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.}}
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.{{cite web | url = https://www.scientificamerican.com/article/some-of-the-parts-is-marijuana-rsquo-s-ldquo-entourage-effect-rdquo-scientifically-valid/ | title = Some of the Parts: Is Marijuana's "Entourage Effect" Scientifically Valid?| vauthors = Chen A |publisher=Scientific American|access-date=2017-12-31 | date = 20 April 2017}}{{cite journal |last1=LaVigne |first1=Justin E. |last2=Hecksel |first2=Ryan |last3=Keresztes |first3=Attila |last4=Streicher |first4=John M. |title=Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity |journal=Scientific Reports|volume=11|page=8232|language=en |doi=10.1038/s41598-021-87740-8 |date=15 April 2021|issue=1 |doi-access=free |pmid=33859287 |pmc=8050080 }} Various terpenes have been found to independently influence behavioral outcomes in mice, with simultaneous administration of CBD and terpene blends having a significantly greater impact than either substance administered independently. {{cite journal
| last1 = Staben | first1 = J
| last2 = Koch | first2 = M
| last3 = Reid | first3 = K
| last4 = Muckerheide | first4 = J
| last5 = Gilman | first5 = L
| last6 = McGuinness | first6 = F
| last7 = Kiesser | first7 = S
| last8 = Oswald | first8 = IW
| last9 = Koby | first9 = KA
| last10 = Martin | first10 = TJ
| last11 = Kaplan | first11 = JS
| title = Cannabidiol and cannabis-inspired terpene blends have acute prosocial effects in the BTBR mouse model of autism spectrum disorder
| journal = Frontiers in Neuroscience
| volume = 17
| pages = 1185737
| date = 15 June 2023
| doi = 10.3389/fnins.2023.1185737
| doi-access = free
| pmid = 37397463
| pmc = 10311644
}}
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.{{cn|date=September 2023}} 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.{{cite journal |author1=Karl W. Hillig |author2=Paul G. Mahlberg |year=2004 |title=A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae) |journal=American Journal of Botany |volume=91 |issue=6 |pages=966–975 |pmid=21653452 |doi=10.3732/ajb.91.6.966|doi-access=free |bibcode=2004AmJB...91..966H }} 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.{{cite journal |vauthors=Niesink RJ, Rigter S, Koeter MW, Brunt TM |title=Potency trends of Δ9-tetrahydrocannabinol, cannabidiol and cannabinol in cannabis in the Netherlands: 2005-15 |journal=Addiction |volume=110 |issue=12 |pages=1941–50 |year=2015 |doi=10.1111/add.13082 |pmid=26234170}}
- Terpene ratios: Sativa ancestry is associated with farnesene and bergamotene, while Indica ancestry is associated with myrcene, elemene, and sesquiterpene alcohols.{{cn|date=September 2023}}
=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.{{Cite journal| doi = 10.1371/journal.pone.0267498| issn = 1932-6203| volume = 17| issue = 5| pages = –0267498| last1 = Smith| first1 = Christiana J.| last2 = Vergara| first2 = Daniela| last3 = Keegan| first3 = Brian| last4 = Jikomes| first4 = Nick| title = The phytochemical diversity of commercial Cannabis in the United States| journal = PLOS ONE| date = 2022| pmid = 35588111| pmc = 9119530| bibcode = 2022PLoSO..1767498S| doi-access = free}}{{Cite journal| issn = 1664-462X| volume = 13| last1 = Murovec| first1 = Jana| last2 = Eržen| first2 = Jan Jurij| last3 = Flajšman| first3 = Marko| last4 = Vodnik| first4 = Dominik| title = Analysis of Morphological Traits, Cannabinoid Profiles, THCAS Gene Sequences, and Photosynthesis in Wide and Narrow Leaflet High-Cannabidiol Breeding Populations of Medical Cannabis| journal = Frontiers in Plant Science| date = 2022| page = 786161| doi = 10.3389/fpls.2022.786161| pmid = 35283868| pmc = 8907982| doi-access = free| bibcode = 2022FrPS...1386161M}}
Background
The phrase entourage effect was introduced in 1999.{{cite journal | vauthors = Ben-Shabat S, Fride E, Sheskin T, Tamiri T, Rhee MH, Vogel Z, Bisogno T, De Petrocellis L, Di Marzo V, Mechoulam R | display-authors = 6 | title = An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity | journal = European Journal of Pharmacology | volume = 353 | issue = 1 | pages = 23–31 | date = July 1998 | pmid = 9721036 | doi = 10.1016/s0014-2999(98)00392-6 }}{{cite news | url = https://edition.cnn.com/2014/03/11/health/gupta-marijuana-entourage/index.html | title = Medical marijuana and "the entourage effect" | vauthors = Gupta S | work = CNN | access-date = 31 December 2017 | date = 11 March 2014 }} 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.{{cite journal | vauthors = Russo EB | title = The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No "Strain," No Gain | journal = Frontiers in Plant Science | volume = 9 | pages = 1969 | date = 2019-01-09 | pmid = 30687364 | pmc = 6334252 | doi = 10.3389/fpls.2018.01969 | doi-access = free | bibcode = 2019FrPS....9.1969R }} 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". 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.{{cite journal | vauthors = Cogan PS | title = The "entourage effect" or "hodge-podge hashish": the questionable rebranding, marketing, and expectations of cannabis polypharmacy | journal = Expert Review of Clinical Pharmacology | volume = 13 | issue = 8 | pages = 835–845 | date = August 2020 | pmid = 32116073 | doi = 10.1080/17512433.2020.1721281 | s2cid = 211726166 | first5 = PS }} The review concluded that the term, "entourage effect", is unfounded and used mainly for marketing.
References
{{Reflist}}
{{Cannabis}}
{{Cannabinoids}}
{{Cannabinoidergics}}