One of the most exciting and promising avenues of cannabis research, capable of unveiling natural chemotypes and formulating products that have surgically precise medical and recreational outcomes, is the entourage effect. With hundreds of cannabinoids, terpenes, and flavonoids found within the cannabis plant, the expanse of potential chemical cocktails that could be created is massive, and the applications are equally diverse. Indeed, its one of the reasons that, when used appropriately, cannabis is the closest thing to a panacea humans have come to know.
What is the entourage effect?
Have you ever been in the middle of making a meal and realized you forgot an ingredient mid prep? Hungry and tired from the previous trip to the grocery, you probably opted to just leave out the ingredient– assuming it wasn’t an important one, like the main protein or…salt. Let me guess: it probably wasn’t as good as the original recipe. The entourage effect is the recipe in this analogy and the cannabinoids, terpenes, and flavonoids are the ingredients. That is to say that the entourage effect is the emergent phenomenon that results from combining the chemical constituents of cannabis to create outcomes that could only have resulted due to the synergy of the multiple ingredients. Think “the whole is greater than the sum of its parts”.
The entourage effect presents itself naturally within any given cannabis plant; the “chemotype” of one nug from one plant varies from the nug of another primarily on the density and ratios of the different cannabinoids, terpenes, and flavonoids. This is the backbone concept behind strains. Different strains of cannabis elicit different medical benefits and recreational effects on the consumer. The entourage effect is a bit like needing to use several keys in order to open your office building, then the room, then safe. It’s not just one key that gets you into the safe. You need a full keyring. Whole plants, like cannabis, are those keyrings and trying to use just one key to get into the safe is like using just THC, instead of all the other cannabinoids together, to solve medical issues.
There is scientific evidence behind the mechanisms of action supporting the entourage effect. In 1999, the Israeli scientist Shimo Ben-Shabat and his team noticed that certain other neurotransmitters in the body could increase the effect of the natural cannabinoid interaction with the receptors. Even just looking at THC and CBD’s interactive effects on the endocannabinoid system (CBD attenuates the ECS response to THC, providing a less jarring high) is another manifestation of the entourage effect in action.
Isolates vs. Broad-Spectrum Formulations
Once THC was discovered to be the active psychotropic ingredient in cannabis, it was quickly bred to be expressed in higher and higher quantities. Amplified by the illegality of the substance, the public perception of cannabis became unidimensional: maximize the number of milligrams of THC per dollar. If you’re going to be risking your freedom procuring a product on the black market, it better pack a punch, right? Sure. If you’re only concern is getting as high as possible, you probably should go ahead and maximize THC. If your interest is, instead, in exploring the multifaceted medical and recreational applications of cannabis, then you can’t collapse cannabis into a single compound. However, isolating and concentrating on a single chemical compound found in a plant has quite a precedent.
Attempting to isolate the active ingredient in medications is common practice when developing pharmaceuticals. For example, the bark from a willow tree contains Salicin which is metabolized in the body to create salicylic acid, a precursor to aspirin. The same logic applies to the Foxglove flower, which is used to make Digitalis.
Pharmaceutical cannabis has taken the same approach in the creation of Marinol (dronabinol)—a THC-only distillate. The same goes for Epidiolex, which is 98% CBD. CBD, given the fact that it does not directly bind with endocannabinoid receptors, but instead modulates the pre-existing activity of the endocannabinoid system, is arguably quite effective in isolation. Nonetheless, the entourage effect can indeed stand to increase the impact of CBD as well. Another FDA approved pharmaceutical developed by GW Pharma, Sativex, at least contains multiple cannabinoids: THC and CBD.
These pharmaceutical preparations of cannabis are typically “isolates” (except Sativex), whereas other products boast “broad-spectrum” or “full-spectrum” preparations, oftentimes presented with various health and outcome claims. Full-spectrum preparations contain all compounds found naturally occurring in the plant, including terpenes, flavonoids, and cannabinoids. Full-spectrum is what would be most aligned with the natural expression of the cannabis plant’s chemotype, able to take full advantage of the entourage effect. Broad-spectrum is the same as full-spectrum, except that it has been stripped of its THC content. This kind of preparation is particularly beneficial to individuals who can not consumer THC for legal reasons, is generally averse to having psychoactive effects on their consciousness, or those at risk for cannabis induced psychosis. Broad-spectrum preparations are typically prepared for CBD products, which is legal throughout the U.S. but prevents the presence of THC, which is still a federally scheduled substance. Broad-spectrum cannabis products would still certainly take advantage of the entourage effect, but would not render the consumer “high”.
While the cannabis market still seems to be pre-occupied with maximizing milligrams of THC or CBD, there is hope that other variables come to light so that consumers can have a richer set of medical applications and recreational experiences with the plant. As additional research comes out on the medical benefits and recreational effects of terpenes and other trace cannabinoids, consumers can begin to procure their cannabis-based on the intended outcome that is more nuanced than just “high” and “really high”. Imagine a product that makes you creative, limits anxiety, and decreases appetite. Imagine another that helps you focus, Again, it’s not just about combining and “stacking” ingredients to collect the benefits of them all; it’s the synergistic and emergent effect of combining multiple compounds to create a new set of effects that may not even be in the repertoire of any one of the ingredients, individually. The building blocks are all there for the industry’s taking; nature has already done a fine job.
“Nature knows best” is far more meaningful than just an adage passed around by hippies who smoked too much dope. A recent article published in the reputable journal Biochemical Pharmacology showed that pure cannabinoid preparations (i.e. isolates) have significantly less antitumor efficacy than “botanical drug preparations” (i.e. full-spectrum).