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Lab Study Fails to Find Evidence of Entourage Effect


We are just in the early days of studying the benefits of the cannabis plant. A new study looks into the possibility that full spectrum CBD oils work better than CBD isolate.


The “entourage effect” is one of the most commonly used terms in the CBD industry. Depending on what type of CBD oil is being sold, it’s often talked about as if it’s a scientifically proven fact – or, alternatively, a total hoax. 

But in these early days of cannabis science, the truth often lies in the complex middle space. Here, scientists test over and over the possible combinations of plant compounds on multiple physiological conditions. 

This process is both costly and slow – and we’re just at the very beginning of it. That’s because the entourage effect is an incredibly complex theory to either prove or disprove. The current study in question, which we’ll dive into below, is an early attempt to test the theory in a very limited setting (which is how science generally proceeds).

But first, what precisely does the entourage effect refer to? 

The idea behind the entourage effect is that the hundreds of different chemicals that make up the cannabis plant – cannabinoids, terpenes, and flavonoids – work together in a way that actually boosts the overall effect of the cannabis extract.

The entourage effect is an incredibly complex theory to either prove or disprove. It means studying hundreds of chemical compounds which interact in complex ways within human bodies.

Proponents of the entourage effect argue that the cannabis plant is polypharmacological, meaning that it has the capacity to engage with multiple targets within our bodies at once. These plant compounds interact with our bodies in complex ways which, according to neuroscientist and cannabis expert Dr. Viola Brugnatelli, can achieve multiple results at once:

“The concept [that each cannabis compound should be tested separately] is as deceptive as judging a choir performance by listening to each of the singers individually….New research in network biology confirms that it is more efficient to hit partially multiple targets than to hit completely a single target.”

This brings us to our present study

Noting that the entourage effect “has not been widely studied scientifically and may prove to be restricted to selected situations,” researchers at Penn State College of Medicine decided to put to the test whether full spectrum CBD oils were better than pure CBD at inhibiting the growth of three different types of cancer cells.

They noted, as part of their motivation, a recent study that found that a botanical drug preparation (what we would refer to as full spectrum oil) was more efficacious for breast cancer than pure THC.

They carefully designed the study to ensure that the full spectrum CBD oil had an equivalent amount of CBD as the pure CBD in the experiments. And all of the CBD extracts they used had certificates of analysis from a third party laboratory. 

Finally, they used equal concentrations of CBD to treat the six cancer cell lines – two lines each of three different types of cancer: brain, skin, and colorectal.

One study that fails to find evidence of entourage does add to our knowledge on the subject, but it doesn't come close to disproving the theory as a whole.

After analysis, the researchers found that CBD  did have an effect on the cancer cell lines – but in regards to any boost in efficacy for the full spectrum extracts, their conclusion was terse: “We did not find any additional efficacy in CBD oils as compared to pure CBD (when matched for CBD concentration).”

So where does this leave us? Is the entourage effect dead?

In short, not even close. As we stated above, we are in the early days of cannabis science and this an extremely complex theory to either prove or disprove. This study isn’t the first and won’t be the last to fail to find evidence of a boost in efficacy for a whole-plant cannabis extract.

For one thing, a single study on six in vitro cancer cell lines doesn’t even begin to account for the other effects that a full spectrum cannabis extract might have on a living human system. As the authors of the study state in their conclusion:

“It is important to recognize that this is a narrow application of using CBD oils to reduce cancer cell viability in culture. We do not suggest that there are no synergistic effects of CBD oil in other clinical settings.”

They also point out the complexity of testing with botanical extracts that vary greatly in their chemical composition:

“The variability in composition and activities of botanical extracts highlights the difficulties in assessing their therapeutic potential compared to pure (or highly purified) chemical entities.

We could go on about this at some length, but suffice it to say that there is a reason the pharmaceutical world has a heavy bias towards single compound formulations – they are a lot easier (and therefore cheaper) to test for efficacy.

We will need many, many more studies to even scratch the surface of the potential polypharmacological effects of cannabis on humans.

It might be a good idea to keep in mind the conclusion of another recent study which also failed to find evidence of synergy between certain terpenes and THC: “The quest for entourage does not end here,” the authors wrote, “in many ways, it has only just begun.”

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