Cannabis Ruderalis

The entourage effect is a proposed mechanism by which cannabis compounds other than tetrahydrocannabinol (THC) act synergistically with it to modulate the overall psychoactive effects of the plant.[1][2]

Compounds[edit]

Cannabinoids[edit]

Cannabidiol (CBD) is under preliminary research for its potential to modify the effects of THC, possibly mitigating some of the negative,[3] psychosis-like effects of THC.

Terpenes[edit]

There are numerous terpenes present in the cannabis plant and variation between strains. Some of the different terpenes have known pharmacological effects and have been studied.[4][5][2]

One supported hypothesis is that myrcene is a prominent sedative terpenoid in cannabis, and combined with THC, may produce the ‘couch-lock’ phenomenon.[2]

Difference between C. indica and C. sativa[edit]

There are several key differences between Cannabis indica and Cannabis sativa. These include height and stature, internodal length, leaf size and structure, buds size and density, flowering time, odour, smoke and effects.[6] Indica plants tend to grow shorter and bushier than the sativa plants. Indica strains tend to have wide, short leaves with short wide blades, whereas sativa strains have long leaves with thin long blades. The buds of indica strains tend to be wide, dense and bulky, while sativa strains are likely to be long, sausage shaped flowers.[7]

During the 1970s, Cannabis indica strains from Afghanistan and Northern Pakistan particularly from the Hindu Kush mountain range were brought to the United States, where the first hybrids with Cannabis sativa plants from equatorial areas were developed, widely spreading marijuana cultivation throughout the States.[8]

The name indica originally referred to the geographical area in which the plant was grown, leading to widespread public taxonomic misconceptions.[9]

Human intervention has produced variation within the species and some authorities only recognize one species in the genus that has had divergent selective pressure to either produce plants with more fiber or plants with greater THC content.[10] Large variability exists within either species, and there is an expanding discussion whether the existing paradigm used to differentiate species adequately represents the variability found within the genus Cannabis.[11][12][13] There are five chemotaxonomic types of Cannabis: one with high levels of THC, one which is more fibrous and has higher levels of CBD, one that is an intermediate between the two, another one with high levels of cannabigerol (CBG), and the last one almost without cannabinoids.[14]

Cannabis strains with relatively high CBD:THC ratios are less likely to induce anxiety than vice versa.[15] This may be due to CBD's antagonistic effects at the cannabinoid receptors, compared to THC's partial agonist effect.[16] CBD is also a 5-HT1A receptor (serotonin) agonist, which may also contribute to an anxiolytic-content effect.[17] The effects of sativa are well known for its cerebral high, while indica is well known for its sedative effects which some prefer for night time use.[17] Both types are used as medical cannabis. Indica plants are normally shorter and stockier than sativas.[18] Indicas have broader, deeply serrated leaves and a compact and dense flower cluster.[citation needed]

Cannabinoids

On average, Cannabis indica has higher levels of THC compared to CBD, whereas Cannabis sativa has lower levels of THC to CBD.[19] 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.[20]

In the recent era of cannabis breeding higher-ratio CBD strains are being developed from Indica origins that may test out as 1:1 (CBD-THC balanced) or even as high as a 22:1 (CBD dominant).

There are three chemotaxonomic types of Cannabis: one with high levels of THC, one which is more fibrous and has higher levels of CBD, and one that is an intermediate between the two.[19][18]

Cannabis strains with CBD:THC ratios above 5:2 are likely to be more relaxing and produce less anxiety than vice versa. This may be due to CBD's antagonistic effects at the cannabinoid receptors, compared to THC's partial agonist effect.[citation needed][dubious ] CBD is also a 5-HT1A receptor (serotonin) agonist, which may also contribute to an anxiolytic-content effect.[17] The effects of sativa are well known for its cerebral high. Users can expect a more vivid and uplifting high, while indica is well known for its sedative effects which some prefer for night time use. Indica possesses a more calming, soothing, and numbing experience in which can be used to relax or relieve pain. Both types are used as medical cannabis.

Plants with elevated levels of propyl cannabinoids, including tetrahydrocannabivarin (THCV), have been found in populations of Cannabis indica from India, Nepal, Thailand, Afghanistan, and Pakistan, as well as southern and western Africa. THCV levels up to 53.7% of total cannabinoids have been reported[19][21]

Terpenes

Sativa ancestry is associated with farnesene and bergamotene, while Indica ancestry is associated with myrcene, elemene, and sesquiterpene alcohols.[22]

Background[edit]

The phrase entourage effect was introduced in 1999.[23][24] 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.[25] 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”.[4] Other cannabinoids, terpenoids, and flavonoids may be part of an entourage effect.[24] The entourage effect is considered a possible cannabinoid system modulator and is achieved in pain management.[1][24][26]

Pharmacology[edit]

Endogenous 2-acyl-glycerols can increase 2-arachidonoylglycerol biological activity, which alone shows no significant activity. This entourage effect may represent a novel endogenous cannabinoid activity molecular regulation route.[23] Cannabinoid system modulators like N-palmitoylethanolamine may exhibit the entourage effect, increasing receptor affinity to enhance endogenous anandamide activity and/or reducing enzymatic anandamide degradation.[26]

Criticism[edit]

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.[27] The review concluded that the term, "entourage effect", is unfounded and used mainly for marketing.[27]

References[edit]

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  2. ^ a b c 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.
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  18. ^ a b Fischedick JT, Hazekamp A, Erkelens T, Choi YH, Verpoorte R (December 2010). "Metabolic fingerprinting of Cannabis sativa L., cannabinoids and terpenoids for chemotaxonomic and drug standardization purposes". Phytochemistry. 71 (17–18): 2058–73. doi:10.1016/j.phytochem.2010.10.001. PMID 21040939.
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  23. ^ a b 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.
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