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] 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. [3]
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. [4] [2] [5]
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.
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. [8] [9]
The phrase entourage effect was introduced in 1999. [10] [11] 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. [12] 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. [11]
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. [13] The review concluded that the term, "entourage effect", is unfounded and used mainly for marketing. [13]
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.