The entourage effect is a well-known theory in medical cannabis and CBD landscapes. This theory suggests that when cannabis compounds are consumed together, they may complement each other's individual characteristics, potentially working together to have more enhanced impact.
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The cannabis plant, and cannabis-based medicines, are made up of different component or compound classes including cannabinoids, terpenes, and flavonoids. It's believed that all three may play a role in the entourage effect.
But first, it’s important to understand:
Cannabinoids are a class of chemical compounds that bind to cannabinoid receptors in our endocannabinoid system. Our bodies naturally produce endocannabinoids to bind with these receptors, and cannabis plants naturally produce phytocannabinoids, more commonly known as cannabinoids, like THC, CBD, CBG, CBN and CBC.
When cannabinoids are consumed they can influence the activity of endocannabinoids and their receptors, to have a variety of potential effects. These are thought to include a reduction of inflammation or pain, relief from anxiety and spasticity, or an improvement in appetite and sleep, meaning they may help some patients manage a variety of medical conditions.
Terpenes are a chemical group naturally produced by plants. Known to contribute to the plant’s aroma and thought to contribute to their therapeutic value in medical cannabis applications, they’re very important.
The cannabis plant is thought to contain around 400 different terpenes, all of which have their own unique properties that might play a role in the entourage effect. Some of the most well known cannabis terpenes are pinene, caryophyllene, limonene and myrcene.
While most research into the entourage effect focuses mostly on the interaction between cannabinoids and terpenes, some scientists believe flavonoids also contribute to the entourage effect.
Flavonoids are a type of natural chemical compound produced by plants, fruits, vegetables, and flowers, including those of the cannabis variety, that are thought to have various beneficial health effects, depending on the type of flavonoid.
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When cannabis is consumed, the cannabinoids and other compounds it contains, enter our bloodstream and then our endocannabinoid system (ECS). The endocannabinoid system spans the body's nervous system and vital organs, and cannabis compounds may be able to enhance, or adjust the functions it is responsible for.
The entourage theory proposes that when cannabinoids, flavonoids, and terpenes are active in the ECS at the same time, the effects that they each have individually, are enhanced.
It is thought that this works in different ways depending on which compounds enter the body. In some cases, this may be by boosting the rate of absorption of other cannabis compounds, whilst in others, it may be by binding to receptors that other compounds are unable to. However, this is yet to be confirmed, so much more research is needed.
The endocannabinoid system's primary function is to restore balance, or homeostasis in the body. It’s therefore thought to regulate our mood, memory, sleep, pain levels, inflammatory and immune responses.
The ECS does this by sending signals or messages to the relevant receptors, using a class of compound called endocannabinoids. When cannabis is consumed, the cannabinoids it contains (like CBD and THC) have the ability to mimic endocannabinoids, and therefore influence the messages the ECS would typically send.
The concept of the entourage effect was first introduced in 1998 by two respected cannabis researchers, Professor Shimon Ben-Shabat and Professor Raphael Mechoulam, who were looking into the endocannabinoid system.
Their proposal was later expanded on by other scientists, including Dr Ethan Russo, who theorised that cannabis might be more pharmacologically effective when consumed as a ‘whole’ than if its individual components, such as THC, were to be consumed alone.
It is assumed the name entourage effect comes from the connotations of the word ‘entourage’ such as an ensemble, a working group, or the idea of being surrounded by associates and assistants.
This is because, in theory, during the entourage effect one type of cannabinoid, such as CBD, is surrounded, and assisted by other cannabinoids, terpenes and flavonoids.
Since 1998, there has been some scientific investigation into Mechoulam and Ben-Shabat’s entourage effect theory.
Although the research is limited, there have been a number of studies that have explored the possibility of the entourage effect. In 2010 a randomised controlled trial suggested that a ‘whole plant’ cannabis extract containing both THC and CBD could potentially be more helpful to cancer patients managing pain than a THC dominant extract that did not contain CBD.
In 2021, more research on the entourage effect theory was published in the Pain Management Journal of Future Medicine. Here, it’s suggested that some patients with pain conditions may have more effective results when using cannabis extracts containing a range of cannabinoids and terpenes than when using an isolated THC extract.
However, the entourage effect has been contested by certain research, including a 2024 paper that underlines the limited evidence that the entourage effect is a predictable phenomenon. Another study suggests that common terpenes don’t change how THC acts at CB1 and CB2 receptors.
The entourage effect has not yet been scientifically proven and much more research is needed before we can draw a conclusion about whether it could be a beneficial phenomenon for medical cannabis patients.
Anecdotal reports suggest that the entourage effect is a full-rounded experience that is more intensely therapeutic than the experience induced when cannabinoids are taken alone.
It is hard to accurately describe how the entourage effect makes a person feel, because everyone's experiences are individual to them. In addition to this, cannabis plants all have a unique blend of cannabinoids, terpenes, and flavonoids, which makes it even more difficult to make a sweeping generalisation or concrete depiction of the entourage effect sensation.
In the UK, cannabis use is only legal if it has been prescribed by a specialist doctor to an eligible patient, for a medicinal purpose, and dispensed by a legal, authorised pharmacy.
Cannabis-based medicines that contain a range of cannabis compounds, like certain prescription cannabis oils or medical cannabis flowers, may have the potential to create the entourage effect because of their chemical makeup.
In the UK, CBD can be purchased on the high street as an isolated extract (mixed with a carrier oil), but also in ‘full spectrum’ or ‘broad spectrum’ products. In CBD isolate products, the only cannabis component present is CBD itself, which can’t induce the entourage effect.
Broad spectrum products contain a range of cannabinoids, terpenes, and flavonoids from the cannabis plant, but THC has usually been removed. Full spectrum products contain a large range of cannabinoids, terpenes, and other natural compounds produced by the plant that the product was extracted from and they usually contain trace amounts of THC. UK regulations dictate that broad spectrum and full spectrum products can contain no more than 1mg of each controlled cannabinoid per container.
Although there is never a guarantee that you’ll experience an entourage effect, full spectrum CBD products are sometimes described as the type of CBD that’s most likely to encourage it.
Unlicensed medical cannabis treatments, like medical cannabis flower and cannabis oils, and licensed cannabis based medicines can be legally prescribed to certain patients in the UK if they are struggling to manage their health condition.
Some licensed medicines, like Sativex and Epidyolex, contain cannabis extracts, while nabilone is a synthetic cannabinoid. Medical cannabis flowers contain cannabinoids, terpenes and flavonoids that can potentially encourage the alleged entourage effect.
Prescribed medical cannabis oils can be formulated into different ratios, containing one sole cannabinoid or a combination of cannabinoids, terpenes and flavonoids, so the potential for the entourage effect depends on the oil's ingredients.
To conclude, the entourage effect theory suggests that the combined consumption of cannabinoids, terpenes, and flavonoids leads to a synergistic, enhanced medicinal or therapeutic effect felt by the body.
This phenomenon, first proposed in the late 90s, implies that whole plant cannabis extracts are more effective than their individual components in isolation, but scientific evidence remains limited.
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