Theentourage effect is a hypothesis thatcannabis compounds, other than thecannabinoidstetrahydrocannabinol (THC) andcannabidiol (CBD), act synergistically with cannabinoids to modulate the overall psychoactive effects of the plant.[1][2] The effect has also been applied in the case ofpsilocybin mushrooms, with other compounds besidespsilocybin having been hypothesized to also contribute to the effects of the mushrooms.[3]
There are numerousterpenes 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] 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.[6]
Cannabinoid ratios: On average,Cannabis indica has higher levels ofTHC compared toCBD, whereasCannabis sativa has lower levels of THC to CBD.[7] 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.[8]
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]
The phraseentourage 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 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.[12]
A 2020 review of research found no entourage effect in most studies, while other reports claimed mixed results, including the possibility of increasedadverse effects.[14] The review concluded that the term, "entourage effect", is unfounded and used mainly for marketing.[14]
^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.PMID37659744.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.
^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.PMID26234170.
^abCogan 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.PMID32116073.S2CID211726166.
