What is the Entourage Effect?

What makes herbal medicine different to pharmaceutical medicine is the understanding that the whole is greater than the sum of its parts. It’s for this reason that botanical preparations usually contain the whole plant rather than a standardized amount of a single compound. With respect to cannabis, this phenomenon is known as the entourage effect.

Though cannabinoids are under heavy scrutiny for their therapeutic effects, they should not be considered outside of the context of the whole plant. The entourage effect dictates that it is the composite work of all chemical entities in cannabis that give it its therapeutic effect. Under this philosophy, isolated cannabinoids are not as therapeutically valuable as whole plant extracts such as broad-spectrum and full-spectrum extracts.

Defining the entourage effect

The entourage effect is only a recent enlightenment of the cannabis industry, and was coined in 1998 by a handful of Israeli chemists. The idea was initially proposed in the context of the endocannabinoid system, as researchers discovered an inactive fatty acid that enhanced the activity of endogenous cannabinoid, 2-AG. Over time, this understanding eventually emerged to include exogenous cannabinoids derived from the cannabis plant.

Essentially, the entourage effect dictates that the therapeutic effect of cannabis is not due to a single cannabinoid, or even to a few cannabinoids. Rather, the effect a person has after using cannabis is due to the combined effect of the 400 chemical entities that are produced by the cannabis plant.

Thus far, four basic mechanisms of this synergy have been established. They are multi-target effects, pharmacokinetic effects (like increased bioavailability), agent interactions, and modulation of adverse events. This essentially means that cannabis is self-regulating in terms of effects; it contains all of the parts it requires to balance its effects, target multiple different parts of the body, and make all of itself available to the body.

The potential of cannabis as a therapeutic agent is not confined to a single cannabinoid, despite the media hype over CBD and THC. The terpenoids and flavonoids present in a specimen of hemp or marijuana are therapeutic in their own right. The degree to which each component interacts with the rest is complex and poorly understood by science. There are, however, some examples of the entourage effect that make the concept very clear.

THC and CBD: A prime example of the entourage effect

THC is the much sought after psychoactive cannabinoid. Most modern strains of cannabis are grown with THC in mind, as this therapeutic cannabinoid is also what makes recreational users attracted to cannabis. But the cannabis plant is not simply a crude delivery mechanism for THC. Interestingly enough, CBD, the second most prevalent cannabinoid in cannabis and the most prevalent in hemp, is non-psychoactive. In fact, CBD is considered an antipsychotic agent.The fact that a single specimen of cannabis should produce two cannabinoids with completely opposite effects is a prime example of the entourage effect.

There is evidence of THC antagonism by CBD — CBD actually reduces the effects of THC, especially those that are undesirable; psychoactivity and tachycardia, for example. This is especially pertinent for modern-day strains of cannabis, which have been bred for high THC content and contain virtually no CBD. This is a world away from cannabis in the 60s and 70s that contained a more balanced ratio of THC to CBD. It also explains why cannabis is much “stronger”, and elicits more adverse events than it did in the past.

The synergy between cannabinoids and terpenes

Cannabis is much, much more than cannabinoids. The compounds present in cannabis that are responsible for its characteristic smell are called terpenes. A single specimen of cannabis can contain multiple different terpenes, giving it a unique aroma, taste, and effect. Terpenes are therapeutic in their own right — it is like cannabis’ very own aromatherapy.

Terpenes also contribute to the effects of cannabis, and they especially contribute to the variation in effects between strains. For example, D-limonene is one of the most abundant terpenes in cannabis (and in nature), and has marked anxiolytic effects. However, its mechanism of action is different to the way CBD produces anxiolytic effects. This suggests potentiation of the anxiolytic effects of CBD by targeting another neuronal circuit that also affects anxiety.

Myrcene is another such example, though rather than being anxiolytic, myrcene exhibits sedative and relaxing properties. It is the sedative component of many hops preparations and likely contributes to the “couch-lock” effect that recreational cannabis users seem to enjoy. On top of this, myrcene diminishes inflammation via prostaglandin-E2.

Caryophyllene, another common terpene in the cannabis plant, also illustrates the synergy between terpenes and cannabinoids. It is the only terpene known to target the cannabinoid receptor, CB1. In this way, it is both a terpene and a phytocannabinoid, and is the only one of its kind. It has anti-inflammatory qualities comparable in its effects to phenylbutazone.

Cannabinoid isolates vs. full-spectrum extracts

Cannabinoid isolates such as CBD isolate and THC isolate are relatively new to the cannabis industry. As their name suggests, the cannabinoid is completely isolated from the rest of its teammates, and isolates are virtually pure cannabinoids. It’s likely that this development was the result of the rise of CBD and cannabis consumers who wanted to completely steer clear of THC. But there is contention about whether isolates can ever have the therapeutic potential of full-spectrum extracts.

Full-spectrum extracts contain, as the name indicates, the full-spectrum of cannabinoids, terpenoids and flavonoids in a single specimen of cannabis. For all intents and purposes, these extracts exemplify the entourage effect.

That’s not to say that isolates don’t have therapeutic value, because they definitely have their medicinal applications. For example, to manufacture cannabis pharmaceuticals, dosages have to be extremely precise and in very strict ratios. This can only occur by isolating compounds and recombining them at the perfect ratios. Plus, certain people just don’t want to use THC for one reason or another, and CBD isolate offers the opportunity to use cannabis without the psychoactive effects of THC.

In the context of herbal medicine, full-spectrum extracts or whole-plant medicines are always preferred. There’s no “messing with nature” per se, as the whole plant is extracted. And though isolates have their place in medicinal cannabis, they can never really match the complexity of the entourage effect and its therapeutic potential.

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