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]

Contents

Compounds

Cannabidiol

Vaped or smoked cannabidiol (CBD), primarily between 250 °C (482 °F) to 300 °C (572 °F), may be converted into THC. [3] Cannabis strains with relatively high CBD:THC ratios have unknown effects on anxiety. [4] [5]

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. [6] [2] [7]

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. [10] [11]

Background

The phrase entourage effect was introduced in 1999. [12] [13] 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. [14] 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". [6] Other cannabinoids, terpenoids, and flavonoids may be part of an entourage effect. [13]

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. [4] The review concluded that the term, "entourage effect", is unfounded and used mainly for marketing. [4]

Related Research Articles

<i>Cannabis</i> Genus of flowering plants

Cannabis is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: Cannabis sativa, C. indica, and C. ruderalis. Alternatively, C. ruderalis may be included within C. sativa, all three may be treated as subspecies of C. sativa, or C. sativa may be accepted as a single undivided species. The genus is widely accepted as being indigenous to and originating from Asia.

<span class="mw-page-title-main">Tetrahydrocannabinol</span> Chemical compound

Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term THC usually refers to the Delta-9-THC isomer with chemical name (−)-trans-Δ9-tetrahydrocannabinol. THC is a terpenoid found in cannabis and, like many pharmacologically active phytochemicals, it is assumed to be involved in the plant's evolutionary adaptation against insect predation, ultraviolet light, and environmental stress. THC was first discovered and isolated by Israeli chemist Raphael Mechoulam in Israel in 1964. It was found that, when smoked, THC is absorbed into the bloodstream and travels to the brain, attaching itself to endocannabinoid receptors located in the cerebral cortex, cerebellum, and basal ganglia. These are the parts of the brain responsible for thinking, memory, pleasure, coordination and movement.

<span class="mw-page-title-main">Cannabinoid</span> Compounds found in cannabis

Cannabinoids are several structural classes of compounds found in the cannabis plant primarily and most animal organisms or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoactive compound in cannabis. Cannabidiol (CBD) is also a major constituent of temperate cannabis plants and a minor constituent in tropical varieties. At least 113 distinct phytocannabinoids have been isolated from cannabis, although only four have been demonstrated to have a biogenetic origin. It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort, and earlier in Echinacea.

<i>Cannabis sativa</i> Plant species

Cannabis sativa is an annual herbaceous flowering plant indigenous to Eastern Asia, but now of cosmopolitan distribution due to widespread cultivation. It has been cultivated throughout recorded history, used as a source of industrial fiber, seed oil, food, recreation, religious and spiritual states and medicine. Each part of the plant is harvested differently, depending on the purpose of its use. The species was first classified by Carl Linnaeus in 1753. The word sativa means "things that are cultivated."

<span class="mw-page-title-main">Cannabinol</span> Naturally-occurring cannabinoid

Cannabinol (CBN) is a mildly psychoactive cannabinoid that acts as a low affinity partial agonist at both CB1 and CB2 receptors. This activity at CB1 and CB2 receptors constitutes interaction of CBN with the endocannabinoid system (ECS).

<span class="mw-page-title-main">Cannabidiol</span> Phytocannabinoid discovered in 1940

Cannabidiol (CBD) is a phytocannabinoid discovered in 1940. It is one of 113 identified cannabinoids in cannabis plants, along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. As of 2019, clinical research on CBD included studies related to anxiety, cognition, movement disorders, and pain, but there is insufficient high-quality evidence that cannabidiol is effective for these conditions. Nevertheless, CBD is a herbal dietary supplement promoted with unproven claims of particular therapeutic effects.

<span class="mw-page-title-main">Tetrahydrocannabivarin</span> Homologue of tetrahydrocannabinol

Tetrahydrocannabivarin is a homologue of tetrahydrocannabinol (THC) having a propyl (3-carbon) side chain instead of pentyl (5-carbon), making it non-psychoactive in lower doses. It has been shown to exhibit neuroprotective activity, appetite suppression, glycemic control and reduced side effects compared to THC, making it a potential treatment for management of obesity and diabetes.

α-Pinene Chemical compound

α-Pinene is an organic compound of the terpene class. It is one of the two isomers of pinene, the other being β-pinene. An alkene, it contains a reactive four-membered ring. It is found in the oils of many species of many coniferous trees, notably the pine. It is also found in the essential oil of rosemary and Satureja myrtifolia. Both enantiomers are known in nature; (1S,5S)- or (−)-α-pinene is more common in European pines, whereas the (1R,5R)- or (+)-α-isomer is more common in North America. The enantiomers' racemic mixture is present in some oils such as eucalyptus oil and orange peel oil.

<span class="mw-page-title-main">Cannabigerol</span> Minor cannabinoid

Cannabigerol (CBG) is one of more than 120 identified cannabinoid compounds found in the plant genus Cannabis. Cannabigerol is the decarboxylated form of cannabigerolic acid, the parent molecule from which other cannabinoids are synthesized.

<span class="mw-page-title-main">Cannabichromene</span> Chemical compound

Cannabichromene (CBC), also called cannabichrome, cannanbichromene, pentylcannabichromene or cannabinochromene, exhibits anti-inflammatory properties in vitro, which may, theoretically, contribute to cannabis analgesic effects. It is a phytocannabinoid, one of the hundreds of cannabinoids found in the Cannabis plant. It bears structural similarity to the other natural cannabinoids, including tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV), cannabidiol (CBD), and cannabinol (CBN), among others. CBC and cannabinols are present in cannabis. It is not scheduled by the Convention on Psychotropic Substances.

<span class="mw-page-title-main">Raphael Mechoulam</span> Israeli chemist (1930–2023)

Raphael Mechoulam was a Bulgarian-born Israeli organic chemist and a professor in the Department of Natural Materials at the School of Pharmacy in the Faculty of Medicine of the Hebrew University of Jerusalem. Mechoulam served as Rector of the university from 1979-1982. He was elected to the Israel Academy of Sciences and Humanities in 1994 and served as its scientific chair from 2007-2013. He was a recipient of the Israel Prize for Chemistry Research in 2000 and the Harvey Prize for 2019-2020.

<i>Cannabis</i> strain Pure or hybrid varieties of cannabis

Cannabis strains are either pure or hybrid varieties of the plant genus Cannabis, which encompasses the species C. sativa, C. indica, and C. ruderalis.

Research has shown that Humulus lupulus and Cannabis sativa are closely related, and it may be possible to create novel cultivars of hops that express valuable chemicals similar to commercial hemp. Both hops and cannabis contain terpenes and terpenoids; tetrahydrocannabinol (THC) is a terpenoid. Hops lack the enzyme that could convert cannabigerolic acid into THC or CBD, but it could be inserted using genetic engineering as was done in 2019 for yeast.

<span class="mw-page-title-main">8,9-Dihydrocannabidiol</span> Chemical compound

8,9-Dihydrocannabidiol is a synthetic cannabinoid that is closely related to cannabidiol (CBD) itself.

<span class="mw-page-title-main">Tetrahydrocannabiphorol</span> Chemical compound

Tetrahydrocannabiphorol (THCP) is a potent phytocannabinoid, a CB1 and CB2 agonist which was known as a synthetic homologue of THC, but for the first time in 2019 was isolated as a natural product in trace amounts from Cannabis sativa. It is structurally similar to Δ9-THC, the main active component of cannabis, but with the pentyl side chain extended to heptyl. Since it has a longer side chain, its cannabinoid effects are "far higher than Δ9-THC itself." Tetrahydrocannabiphorol has a reported binding affinity of 1.2 nM at CB1, approximately 33 times that of Δ9-THC (40 nM at CB1).

<span class="mw-page-title-main">Δ-8-Tetrahydrocannabinol</span> Isomer of tetrahydrocannabinol.

Δ-8-tetrahydrocannabinol is a psychoactive cannabinoid found in the Cannabis plant. It is an isomer of delta-9-tetrahydrocannabinol, the compound commonly known as THC.

<span class="mw-page-title-main">Hexahydrocannabinol</span> Hydrogenated derivative of THC

Hexahydrocannabinol (HHC) is a hydrogenated derivative of tetrahydrocannabinol (THC). It is a naturally occurring phytocannabinoid that has rarely been identified as a trace component in Cannabis sativa, but can also be produced synthetically by hydrogenation of cannabis extracts. HHC was first synthesized in 1944 by Roger Adams using natural THC found in Cannabis sativa.

<span class="mw-page-title-main">Tetrahydrocannabihexol</span> Chemical compound

Tetrahydrocannabihexol is a phytocannabinoid, the hexyl homologue of tetrahydrocannabinol (THC) which was first isolated from Cannabis plant material in 2020 along with the corresponding hexyl homologue of cannabidiol, though it had been known for several decades prior to this as an isomer of the synthetic cannabinoid parahexyl. Another isomer Δ8-THCH is also known as a synthetic cannabinoid under the code number JWH-124, though it is unclear whether this occurs naturally in Cannabis, but likely is due to Delta-8-THC itself being a degraded form of Delta-9-THC. THC-Hexyl can be synthesized from 4-Hexylresorcinol.

Cannabinoids are compounds found in the cannabis plant or synthetic compounds that can interact with the endocannabinoid system. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (Delta-9-THC), the primary intoxicating compound in cannabis. Cannabidiol (CBD) is another major constituent of some cannabis plants. At least 113 distinct cannabinoids have been isolated from cannabis.

Chemical defenses in <i>Cannabis</i> Defense of Cannabis plant from pathogens

Cannabis (/ˈkænəbɪs/) is commonly known as marijuana or hemp and has two known strains: Cannabis sativa and Cannabis indica, both of which produce chemicals to deter herbivory. The chemical composition includes specialized terpenes and cannabinoids, mainly tetrahydrocannabinol (THC), and cannabidiol (CBD). These substances play a role in defending the plant from pathogens including insects, fungi, viruses and bacteria. THC and CBD are stored mostly in the trichomes of the plant, and can cause psychological and physical impairment in the user, via the endocannabinoid system and unique receptors. THC increases dopamine levels in the brain, which attributes to the euphoric and relaxed feelings cannabis provides. As THC is a secondary metabolite, it poses no known effects towards plant development, growth, and reproduction. However, some studies show secondary metabolites such as cannabinoids, flavonoids, and terpenes are used as defense mechanisms against biotic and abiotic environmental stressors.

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. ↑ Czégény, Z; Nagy, G; Babinszki, B; Bajtel, Á; Sebestyén, Z; Kiss, T; Csupor-Löffler, B; Tóth, B; Csupor, D (26 April 2021). "CBD, a precursor of THC in e-cigarettes". Scientific Reports. 11 (1): 8951. Bibcode:2021NatSR..11.8951C. doi:10.1038/s41598-021-88389-z. PMC   8076212 . PMID   33903673.
  4. 1 2 3 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.
  5. ↑ Russo EB, Tyler VM (22 December 2015). Handbook of Psychotropic Herbs: A Scientific Analysis of Herbal Remedies for Psychiatric Conditions. Routledge. pp. 233–. ISBN   978-1-136-38607-7.
  6. 1 2 Chen A (20 April 2017). "Some of the Parts: Is Marijuana's "Entourage Effect" Scientifically Valid?". Scientific American. Retrieved 2017-12-31.
  7. ↑ 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: 8232. doi: 10.1038/s41598-021-87740-8 .
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. 1 2 Gupta S (11 March 2014). "Medical marijuana and "the entourage effect"". CNN. Retrieved 31 December 2017.
  14. ↑ 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.
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