What Is the Entourage Effect?

Cannabidiol Oil

Did you know that cannabidiol oil contains more than just, well, cannabidiol?

Seriously — premium cannabidiol oil contains dozens and dozens of unique compounds that work together within your body. This synergy is known (and loved, of course!) as the entourage effect. This article will dive deep into the entourage effect and show you how you can harness it for yourself. 

The Entourage Effect 101

First things first — let’s dive a little deeper into what the entourage effect is. And for that, a bit more context is needed. 

An intriguing trend is surfacing within many parts of the scientific community. Biochemists and pharmacologists are learning that whole-animal/whole-plant/whole-herb supplements work better than isolated compounds. What’s more, the apparent benefits of isolated compounds don’t always play out in real life, even if they appear real in the lab. 

Here’s a practical example. Decades ago, science learned about the importance of essential fatty acids, like omega 3’s or 9’s. In vitro, the benefits of these compounds couldn’t have been much more apparent, but in vivo (i.e., in real life), the benefits of supplemental omega 3’s are much less clear. Some real-world studies done in humans have found no benefits to omega 3 supplementation, at all. Eating a diet rich in seafood, however, has been proven beneficial again and again.  

See the concept at play here? Something similar seems to happen with cannabidiol; isolated cannabidiol doesn’t always work as well in real life as it does in the lab. To really harness its power, we also need to harness the power of nature. 

And that’s done best by keeping cannabidiol within the matrix of other beneficial compounds it’s found within nature. 

Why is cannabidiol’s compound+compound synergy called “the entourage effect”? That just refers to how hemp’s other active ingredients form an entourage with cannabidiol and help shuttle it to its cellular targets. If you’ve ever felt more alive or more confident when surrounded by a group of close friends, well, cannabidiol seems to feel the same. 

And the entourage effect isn’t just something subtle, either. Cannabidiol works a lot better when taken in natural, whole plant form. One study out of Israel found that a cannabidiol-rich cannabis extract performed four times better than cannabidiol isolate. In addition to being more effective, this extract was easier to dose, in the sense that side effects weren’t observed even at suboptimal dosing. And in case you’re wondering, yes — this study was done in real people.  

It is likely that other components in the extract synergize with [cannabidiol] to achieve the desired anti‐inflammatory action that may contribute to overcoming the bell‐shaped dose‐response of purified [cannabidiol].

Overcoming the Bell‐Shaped Dose‐Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol. Pharmacology & Pharmacy

The critical role of terpenes

This is all good stuff, you may be thinking, but how does the entourage effect work? 

Once we move past metaphorical descriptions, the inner workings of the entourage effect get pretty complicated. But most of its mechanisms go back to one particular group of “other components” — the terpenes.  

You can think of terpenes as hemp’s specialized scent molecules. They give the plant its characteristic earthy, skunky, forest-y smell. They also give hemp extracts like cannabidiol oil much of their power.  

How do terpenes contribute to the entourage effect? Possibly by changing the way cannabidiol binds to CB2 endocannabinoid receptors. Think of these special receptors as little baskets that cannabidiol can sink into, and think of terpenes as smaller molecules that weigh down the baskets so more substantial amounts of cannabidiol can sink in. Scientists call this effect conformational change

Terpenes are also known “permeability enhancers” that may help cannabidiol absorb more deeply through the mucus membranes, digestive tract, or skin. A hemp-derived terpene called limonene, for example, may be especially effective at boosting cannabidiol’s transdermal absorption. Other terpenes, like myrcene or linalool, have impressive anti-inflammatory benefits of their own.

Another thing to keep in mind: full-spectrum cannabidiol oil doesn’t just contain one or two terpenes. It contains dozens of them, at least. Science has yet to ascertain how all these compounds might work together fully, but we do have the 4 x more powerful figure from the Israel study to look to. 

What you need to know about flavones

Another class of molecules that contributes to the entourage effect is the flavones. Also called flavonoids, these compounds are found throughout nature. But hemp is unique in that it contains at least two flavones — cannflavin A and cannflavin B — not found anywhere else.

And these trace compounds may be some of hemp’s most potent. Research from way back in the 80s found that cannflavin A and B’s painkilling properties were 30 times more potent than aspirin’s. They seem to inhibit the very formation of inflammatory molecules, called prostaglandins, en route to holistically reducing pain. Some researchers today even hope that the cannflavins will be used to replace opioids.

Does all cannabidiol oil create the entourage effect?

The short answer is no. 

That’s not surprising if you think about it. Only cannabidiol oils that feature an entourage of additional ingredients, above and beyond cannabidiol, can harness the entourage effect. 

We’ve said it before, but we’ll say it again: not all cannabidiol is created equal. Only oils that feature a full spectrum of hemp’s cannabinoids, terpenes, and flavones fully engage the entourage effect. Some scientists think that tetrahydrocannabinol is also needed, and, like the terpenes mentioned earlier, it may also ‘open up’ endocannabinoid receptors so that cannabidiol can bind to them more fully. And if that’s the case, even broad-spectrum cannabidiol oil wouldn’t be ideal. 

To put it simply, the more active ingredients present, the better. Cannabidiol + tetrahydrocannabinol + trace cannabinoids + terpenes + flavones + chalcones + plant waxes = far more plant power than cannabidiol itself. 

Interpreting new research

As great as the entourage effect is, not everyone is a total believer. Some scientists called it into question in an appropriately-titled 2019 study called “Absence of Entourage…” The study found that many of hemp’s most important terpenes didn’t change cannabinoid receptors enough to make any difference in tetrahydrocannabinol’s absorption. Though this study seemed set on proving its title was correct, its authors did acknowledge that cannabinoids and terpenes could work together through other pathways. 

And why wouldn’t they? Real-world review studies have found that cannabinoids and terpenes can improve one’s mood when coupled together. These compounds must be working through other pathways. Indeed, both cannabinoids and terpenes can affect TRPV receptors, GPR155 receptors, Adenosine A2A receptors, and leptin receptors serotonin receptors, dopamine receptors, GABA receptors, PPAR’s, and more. Suffice to say that the “Absence of Entourage” study fell far short of grasping the scope of hemp’s activity. 

For now, there’s not much we can do but trust real-world results over incomplete studies and await some better data. In the end, after all, nature is usually proven right.