Does the entourage effect explain the effects of cannabis? Or is it based more on wishful thinking than science?

There is no shortage of discussion on the entourage effect these days. Within the cannabis sphere, everyone talks about it like it is the most important thing in the world. This effect describes how different molecules in cannabis interact with each other to give an effect that is “greater than the sum of its parts”.

Now the entourage effect has gone mainstream – it was recently covered by Scientific American.

This article paints the entourage effect as a big controversy. Is it real, or is it all a scam by cannabis startup companies to market their products? “Industry players swear pot’s many chemicals work in concert, but most scientists hear a THC solo”. I guess controversy sells!

Out of 5 scientists interviewed, 3 absolutely believed in the entourage effect (while admitting it is understudied), and 2 believed that an entourage effect could exist, but didn’t think there was enough data yet to say. Hmm, that doesn’t sound quite as dramatic.

The article is heavy on interviews and light on actual science. But when it does go into the science, it gets it wrong:

Still, there is no hard evidence that the entourage effect is real. Double-blind clinical trials, the gold standard for research studies in medicine, have never been conducted to investigate the effects of marijuana’s terpenes or its cannabinoids other than THC.

This statement is incorrect. There have been double-blind, placebo-controlled clinical trials of both CBD alone and how CBD and THC work together. I’m not saying that we understand everything about it, but the number of these studies definitely isn’t zero. The author of this article apparently couldn’t do a comprehensive scientific literature search.

As one of the interviewed medicinal cannabis researchers said: “The internet is great but it has a lot of fake news.”

[Flickr/ Gage Skidmore]

So what is real and what is fake when it comes to the entourage effect? How much science is there to back up the various claims? I have read enough misinformation on this topic, both from people promoting it and people denouncing it. I will now be dedicating the time to write a series of articles to sort this out for you.

What is the Entourage Effect?

The entourage effect (also sometimes called the ensemble effect) describes how multiple chemical constituents of cannabis have a different (presumably better) action than when isolated constituents are given alone.

This is an incredibly broad definition, so let me break it into two specific groups:

  • Improved efficacy/high: Cases where combining more than one constituent of cannabis improves a desired therapeutic effect or type of high
  • Improved tolerability: Cases where combining more than one constituent of cannabis decreases the incidence or severity of an unwanted side effect

These two types of entourage are also linked – by improving tolerability, higher doses can be taken, which may then improve efficacy (or just allow you to get really high if that’s what you’re after).

Why Is There So Much Confusion Around the Entourage Effect?

The entire  discussion around the entourage effect is hampered by overly broad generalizations. People talk about it like the entire concept is true or false. We have to look at each individual example of the entourage effect and examine the evidence.

Some examples have a lot of evidence. One person can point to these examples and say, “see? the entourage effect is real.” Another person will point to a different example with a big claim, but little evidence, and say “see? the entourage effect is false”.

[Pixabay]

Cannabis has been proposed to treat conditions ranging from pain to seizures to mood disorders to neurodegenerative diseases to cancer. Cannabis does not necessarily act in every disease the same way.  After all, THC and CBD can potentially act at over a dozen different targets within the cell.

In different diseases, it is possible that:

  • There is not any appreciable entourage effect
  • There is an entourage effect and it helps
  • There is an entourage effect and it is detrimental

We still have a long way to go in understanding the details. It is a lack of research that is the main reason behind the confusion. This is something that almost everyone agrees on.

Is the Entourage Effect Exclusive to Cannabis?

The entourage effect is a term used exclusively by the cannabis community. But the concept that a single molecule is not enough to treat a disease is neither new nor controversial.

Drug combinations are used across almost every therapeutic area. Drug cocktails are routinely given for HIV and hepatitis C treatment. Most cancer treatment regimens consist of drug combinations (and then usually more drugs on top of that to control the side effects). Autoimmune diseases, mood disorders, and many other diverse diseases all have treatment options with drug combinations.

Just like with the cannabis entourage effect, drug combinations are used for the same two reasons: the combination has better efficacy than one drug alone, or one drug improves the side effects of the other.

Do You Need the Whole Plant for the Entourage Effect?

Some claim that the future of cannabis-based medicine will always be the whole plant:

Smoking marijuana provides benefits that no pharmaceuticalized pill or liquid version of cannabis can match.

There is no formula in cannabis that cannot eventually be recreated by blending isolated molecules together. Everything feels a bit like magic when we don’t understand it. The only reason we don’t understand more details of the entourage effect is a lack of research. However, this is slowly changing.

For example, ebbu is a company that is isolating individual cannabinoids and terpenes, testing them in different combinations in cellular pharmacology assays, and then testing formulations with different ratios in people.

Does this mean there is no future for whole plant cannabis? I suspect not, as there will always be people who prefer this method. Just as a person with depression may choose to go to their doctor to get a prescription antidepressant, others will prefer to try an herbal extract like St. John’s Wort or consume raw herbs.

[Max Pixel]

How Many Molecules in Cannabis Have an Entourage Effect?

There are some who seem to think that it takes every single molecule in the cannabis plant to produce this effect:

This phenomenon, called the “entourage effect,” results when hundreds of natural components within a plant interact together

Yes, there are hundreds of chemicals in cannabis. There are also hundreds of chemicals in carrots. Only a few of these will turn out to really matter. Although there are dozens of cannabinoids and over 100 terpenes found in cannabis, the majority of these molecules are in quantities so low that they are irrelevant.

So how many different cannabinoids and terpenes can potentially synergize together? The truth is that we don’t yet know. Many are suspected, but few are proven. I will be giving various examples in my upcoming articles.

Is the Entourage Effect Real?

If proving one single example of the entourage effect means it’s real, then yes, the entourage effect is real. In one case, there are multiple, well-controlled clinical studies from independent laboratories that are in agreement that the effects of THC are modified by another constituent of cannabis a very beneficial way. I am going to write about it in the next article!

In reality, the answer is complicated. So many people talk about the entourage effect in black and white, as if it is entirely true or entirely false.

All examples of the entourage effect have varying degrees of evidence. Maybe it was shown in an animal study, but we aren’t sure if it applies to humans. Maybe there is a lot of anecdotal evidence, but no actual studies to back it up. Maybe my cousin’s roommate’s boyfriend read it on the internet and swears it’s true.

Maybe tomorrow we will wake up to a new Trump tweet: Prof of Pot said there is no evidence that pinene prevents THC-induced memory loss? FAKE NEWS! My OG Kush is fantastic!!

My point is that each individual example needs to be assessed to see how much evidence there really is. And that’s exactly what I will do in this series of articles…stay tuned!

[Featured image credit: Flickr/ FAN THE FIRE Magazine]

Last modified: June 18, 2017

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