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What is the entourage effect? A guide to CBD synergy and how to benefit from it

The entourage effect is the mechanism by which cannabis compounds work together in synergy. Learn how to harness the full power of cannabis.
The entourage effect
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Full plant = Full benefits

Has your doctor ever told you that eating fruits and vegetables is better for you than taking a vitamin supplement? Well, it turns out that the same may be said of cannabis and hemp, as a whole-plant extract could potentially impart greater effects than any single compound in the plant.

The reason for this is a phenomenon called the “entourage effect”. But what is the entourage effect, and is there any scientific evidence to prove that it exists?

In this article, we’re going to look at the entourage effect in greater detail, explaining why whole-plant extracts (aka full-spectrum) CBD products are often preferred over pure, isolated CBD extracts.

Entourage effect 101

Cannabis and hemp plants are both part of a complex plant genus called Cannabis Sativa. C Sativa contains a large number of biologically active compounds that are able to impact our biological processes and bodily function in a variety of ways.

Most people have heard of the cannabinoids THC and CBD but they are just two of well over 100 cannabinoids that have been identified in Cannabis Sativa plants by scientists over the last few decades. Further to that, over 150 different terpenes and 20 different flavonoids have been identified, all of which contribute to the overall unique properties offered by a specific cannabis or hemp strain.

What research seems to be showing us, however, is that the potential therapeutic benefits offered by a strain go above and beyond the effects of its contributing parts, thanks to the full spectrum entourage effect.

Full-Spectrum CBD

What is the entourage effect?

The entourage effect is a proposed mechanism by which many compounds found in cannabis, including cannabinoids and terpenes, work together in synergy to provide more enhanced effects, suggesting that the entirety of the whole plant’s effect is greater than the sum effects of its contributing parts.

The existence of the entourage effect suggests that certain compounds found in cannabis behave differently when certain other compounds are present. The same way your behavior may alter in different social situations, depending on who else is present.

THC has long been used as an effective analgesic and in 2010 a clinical study was conducted on cancer patients with intractable pain. Some were given a pure THC extract, while others were given THC and CBD in equal parts and the subjects receiving the combination of THC and CBD reported significantly less pain.

The team of researchers working on this study commented that, “CBD may enhance the analgesic potential of THC by means of potent inverse agonism at CB2 receptors, which may produce anti-inflammatory effects, along with its ability to inhibit immune cell migration.

The difference between CBD isolate and full spectrum CBD

The first time I came across the concept of the cannabis entourage effect was while reading a 2015 paper on Scientific Research Publishing online. The paper was entitled Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol.

This compelling research studied the anti-inflammatory and antinociceptive (pain-blocking) activities of potential cannabis synergy by studying the effects of single molecule CBD alongside a full-spectrum cannabis extract, named clone 202. Clone 202 was a whole-plant extract, so it contained many different cannabinoids and cannabis compounds, but researchers specifically noted that it was high in CBD and low in THC.

When the single molecule CBD was administered to mice, the scientists discovered that while it did exhibit anti-inflammatory and analgesic activity, it resulted in a bell-shaped dose-response curve. This means that it not only stopped being effective at a certain dose (represented by the top of the bell), but it then began to reduce in effectiveness at higher doses.

However, when clone 202 was administered, the bell-shape disappeared and the extract continued to become more and more effective as the dose increased.

Galilly and her team concluded that “It is likely that other components in the extract synergize with CBD to achieve the desired anti-inflammatory action that may contribute to overcoming the bell-shaped dose-response of purified CBD. We therefore propose that Cannabis clone 202 (Avidekel) extract is superior over CBD for the treatment of inflammatory conditions.

But the entourage effect doesn’t just enhance these compounds’ ability to fight pain and inflammation, as further research on human breast cancer cell lines also supports the existence of the entourage effect.

In 2018, a team of scientists showed that a cannabis extract treatment demonstrated superior anti-tumor activity to pure THC. They attribute this success to small concentrations of cannabigerol (CBG) and tetrahydrocannabinolic acid (THCA) being present.

And the evidence continues…

A meta-analysis paper published in 2018 also supported the existence of cannabis compound synergy, having combined the results of 11 different clinical studies that examined the effects of CBD on seizures.

This paper split the data from these studies, which involved 670 patients in total, into results that had been achieved from CBD-rich cannabis extracts vs purified CBD. The results showed that 71% of patients improved with CBD-predominant cannabis extracts vs 36% of patients on pure CBD.

Another interesting finding to come out of this study was an observation made on doses. The mean daily doses were markedly different in the two groups, with 27.1mg/kg per day for purified CBD and just 6.1mg/kg per day for CBD-rich cannabis extract.

This means that whole-plant cannabis extract wasn’t just achieving significantly better results, but it was also doing so at just 22% of the dose of the pure CBD. Perhaps unsurprisingly, the incidence of adverse effects was also demonstrably higher in the CBD-only patients, presumably due to the higher dose given.

It was the authors opinion that the CBD-rich cannabis extract showed greater efficacy due to “the synergistic contributions of other entourage compounds. Such observations support the hypothesis of greater efficacy for Cannabis extracts combining multiple anticonvulsant components, such as CBD, THC, THCA, THCV, CBDV, linalool, and even caryophyllene”.

How CBD and THC work together

As mentioned above, CBD and THC work together to offer more enhanced therapeutic benefits, but that’s not where their synergy begins and ends. Although CBD is able to amplify the pain-relieving effects of THC (and vice-versa), it can simultaneously decrease the psychoactive effects that THC imparts.

The intoxicating properties of THC have long held back the widespread use of this compound in medicine, but a 2006 paper showed that CBD is able to significantly reduce some of the more undesirable effects of THC, including intoxication, sedation, and tachycardia.

Researchers believe that CBD is able to decrease THC’s psychoactive effects via antagonism at type 1 cannabinoid receptors (CB1) and a combination THC:CBD medication would potentially provide a far more attractive safety profile for chronic medicinal use.

In the UK, there is already a THC:CBD medication which is approved and available on prescription for multiple sclerosis sufferers, called Sativex. Sativex is made by the same pharmaceutical giant that brought us Epidiolex,  an FDA-approved, CBD-based medication available in both the US and the UK).

According to Dr. Ethan Russo, a psychopharmacologist and expert in cannabis research, CBD is the biggest influence in the entourage effect. Dr. Russo says that around 10mg of THC can potentially cause toxic psychosis in around 40% of people. However, when administered on a 1:1 ratio with CBD, like in the medication Sativex, a much larger dose of 48mg of THC causes this toxic psychosis in just four patients out of 250.

He notes that this is a very important demonstration of cannabis synergy and notes that other cannabinoids may display similar synergy, they just haven’t been studied yet.

How to enhance CBD effects

If we’re to listen to the evidence and believe that this entourage effect exists then the best way to enhance the effects of CBD is to take it in a full-spectrum product that contains all of the naturally occurring major and minor cannabinoids, terpenes, and other plant compounds, just as Mother Nature intended.

If you live in a zero-THC tolerance state or are worried about failing a drug test, then broad-spectrum products are the next best thing, but try to select products that keep their formulas as natural as possible, removing the THC only.

If you’ve already invested a lot of money in CBD isolate products, then there are still many ways you can benefit from the CBD entourage effect. Here are just some of the ways I’ve seen CBD isolate being used more effectively:

Mix with full-spectrum products

Take your CBD isolate oil, capsule, or gummy, alongside any other full-spectrum product to increase the overall concentration of CBD. This could be especially helpful at nighttime when you want to increase your dose of CBD to benefit from the sedative powers of CBD (only displayed at higher doses). You can learn more about the CBD and sleep here.

Mix with high-THC products

I’ve also seen people that roll cannabis joints or take THC dabs with CBD powder to soften and level out their THC buzz. You can easily add a CBD concentrate to your joint or bowl of cannabis flower, or coat your THC wax or resin with it before dabbing it.

Any CBD product can easily be combined with a high-THC product to reduce the intoxication levels felt, as well as boost the pain-relieving and anti-inflammatory properties.

Take your CBD isolate with Delta 8 THC

If you don’t have access to legal cannabis in your state, then you may still be able to get hold of some federally legal Delta 8 THC, to mix with your CBD isolate. Hemp-derived Delta 8 THC is legal under the Hemp Farming Act of 2018 and can be found online at countless vendors.

However, it’s important to check whether Delta 8 THC is legal in your state, as some states have banned all forms of THC outright, as well as learn how to spot a good product (read our article “is Delta 8 safe?”, here).

Mixing your CBD isolate with Delta 8 THC may enhance many of the effects of CBD, but you should be aware that it does also carry psychoactive effects, around half as potent as its more famous sister, Delta 9 THC.

What does the entourage effect feel like?

We’re often asked, what does the entourage effect feel like? But the term is used to describe many different types of cannabis compound synergy, so it’s difficult to offer just one explanation!

For example, if you add some CBD isolate powder to your next medical marijuana joint, then it may mean that you feel less stoned or high than usual. In addition to this, it’s likely that you’ll also feel more pain-relief and sleep better at night.

Elsewhere, the entourage effect could result in a life-saving treatment for MRSA, a treatment resistant bacteria that caused more than 100,000 deaths in 2019 alone. Both the CBD and CBG cannabinoids and the terpene pinene have all been shown to powerfully inhibit MRSA. So, a whole plant extract of a CBD and CBG-rich hemp chemovar that also expresses pinene could offer an excellent and safe new antiseptic agent.

How to take advantage of the entourage effect

The easiest way to ensure you’re getting the full spectrum entourage effect from your CBD product is to invest in pure, unadulterated CBD flower. Buying and consuming CBD flower means you’re experiencing all of the naturally-occurring hemp compounds, just as mother nature intended.

You can smoke or vape CBD flower, but if you don’t like the idea of inhaling anything, then you can also consider making your own CBD oil, so you can enjoy strain-specific entourage effect action.

Or, if you’re looking for a more convenient product and want to feel the full entourage effect from CBD gummies (for example), you should look for full spectrum CBD gummies or (at the very least) broad-spectrum gummies. Just be aware that broad-spectrum gummies, although they’re more widely available, may not be as effective when it comes to pain management as those that have THC in them, even if it is just a trace amount.

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