Most people will be familiar with the concept that different cannabis strains can produce varying effects, but you might be wondering what exactly makes canabis so versatile. The answer may have to do with the entourage effect – the theory that terpenes and flavonoids work together with the two most famous cannabis compounds, tetrahydrocannabinol (THC) and cannabidiol (CBD) along with minor cannabinoids such as cannabigerol (CBG) and cannabinol (CBN) to create a therapeutic effect
What does ‘work together’ mean exactly? Researchers are studying that very question and we don’t have concrete answers yet. The entourage effect is a relatively new area of cannabis research – the term was coined in a 1998 paper by Raphael Mechoulam, who has been called ‘the father of cannabis research.’
In their influential study, Mechoulam and his colleagues suggested that cannabis products may be more medically beneficial when the entire spectrum of the plant is included, rather than extracts that only contain specific compounds. Much like a team working to support each other, the long list of minor and major compounds in cannabis may work together harmoniously to produce greater therapeutic effects.
So what does this mean for medical cannabis today, and should you take the entourage effect into account when starting medical cannabis treatment?
Is The Entourage Effect Unique To Medical Cannabis?
Although the entourage effect is usually associated with medical cannabis, the idea of compounds working together is found in many natural medicines, pharmaceuticals and foods.
A useful way to understand the entourage effect is to think of the many diverse animal and plant species in an ecosystem interacting with one another. Every species in a healthy ecosystem has unique roles and relationships that contribute to the ecosystem’s overall health and stability.
The same thing may apply to medicines such as cannabis, which contains hundreds of different compounds that may potentially synergise and contribute to a greater therapeutic effect.
What Are Cannabinoids And How Do They Contribute To The Entourage Effect?
Cannabinoids can be split into two main categories: endocannabinoids and phytocannabinoids. Your body produces endocannabinoids such as anandamide (commonly known as the ‘bliss molecule’) regardless of whether you consume cannabis, whereas phytocannabinoids such as THC and CBD are introduced to the body through consuming cannabis.
All cannabinoids act on your endocannabinoid system – a complex network of receptors and chemical signals throughout the brain and body that helps regulate several bodily functions. There are two types of cannabinoid receptors in the endocannabinoid system: CB1 and CB2 receptors. THC has more affinity for CB1 receptors, while CBD binds to CB2 receptors. Some cannabinoids such as anandamide partially affect both cannabinoid receptors.
Along with THC and CBD, there are more than 100 other minor cannabinoids, such as cannabigerol (CBG), cannabichromene (CBC) and cannabinol (CBN), which may also be involved in the entourage effect.
THC is responsible for the psychoactive effects of cannabis, while CBD may reduce some of its side effects such as anxiety and fatigue. This is one example of how cannabinoids can work together to create a beneficial entourage effect.
Cannabinoids aren’t the whole story, however. Other compounds in cannabis such as terpenes may be involved in the entourage effect as well.
What Are Terpenes And Are They Involved In The Entourage Effect?
Terpenes are aromatic compounds that determine how a plant smells and tastes. Some terpenes you would be familiar with include limonene, responsible for the citrusy scent of lemons, and linalool, which is present in lavender and creates its soothing aroma.
Both of these terpenes are also found in certain cannabis strains, along with myrcene, pinene, humulene and many more. The terpenes present in a cannabis strain depends on the effect the grower is trying to achieve.
Researchers aren’t yet sure the exact way terpenes influence the effects of cannabis. However, a recent review of the evidence suggested that terpenes may enhance the effects of THC and/or CBD, but that more clinical research is needed to confirm this.
Another review suggests that inactive compounds such as terpenes may contribute to an entourage effect by delaying the rate at which active compounds like THC degrade, or by affecting the way active compounds bind to cannabinoid receptors.
Studies in this review also mention a variety of potential therapeutic benefits certain terpenes may have on their own, including anti-inflammatory properties, pain relief, anxiety relief, antidepressant and sedative effects. These results come from preclinical studies, meaning the effect terpenes may have on humans haven’t been well-studied.
Some research is sceptical of the role terpenes may play in the entourage effect. One study found evidence to suggest that terpenes may not directly affect cannabinoid receptors. This may mean that if cannabis terpenes are involved in an entourage effect, it’s likely through a mechanism other than directly affecting the CB1 and CB2 receptors.
Another recent study supports the notion that terpenes aren’t active at cannabinoid receptors. The authors don’t dismiss the idea of the entourage effect but they do suggest it needs more clarification and research.
Does The Entourage Effect Have Medical Significance?
Currently the evidence is inconclusive. Researchers have noticed that whole cannabis extracts may sometimes have more therapeutic benefits and fewer side effects than purified cannabis extracts, suggesting the entourage effect may be at play. A 2018 meta-analysis found that CBD-rich extracts were more effective in treating patients with epilepsy compared to purified CBD products. Patients treated with CBD-rich extracts tended to experience fewer negative side effects and on average required a lower dose to receive therapeutic benefits compared with purified CBD. The researchers speculated that the superior therapeutic effect of CBD extracts might be due to the extra compounds in the CBD extracts creating an entourage effect.
An older study also found that cancer patients reported lower pain scores after receiving a medication that combined THC and CBD, compared to those who received an isolated THC medication.
There aren’t a lot of high-quality human studies to support the idea of the entourage effect having medical significance. However, anecdotal reports indicate a preference for cannabis products that contain multiple cannabinoids, terpenes and other compounds rather than isolate products that only contain THC or CBD.
Whether you would respond better to a full-spectrum medical cannabis product or an isolate extract is something you should discuss with your doctor. There are many different medical cannabis formulations & applications designed to help manage a wide variety of conditions.
Unpacking The Entourage Effect
Cannabis sativa is a versatile and complex plant with a long list of medical uses. There’s a lot we still don’t know about how cannabinoids, terpenes and other compounds in cannabis interact with each other. But we do know that THC and CBD complement each other in a variety of beneficial ways and that this relationship might extend to hundreds of other cannabis compounds.
We’re learning more and more about medical cannabis through controlled clinical trials and the collective wisdom of the medical cannabis community. Soon, we’re likely to hear more discussion and revelations around the entourage effect and how it might help drive the future of medical cannabis.
In the meantime, the best person to speak with about how you might benefit from medical cannabis and the entourage effect is your doctor. Many people live with conditions that don’t respond well to conventional treatments. If this sounds familiar, we recommend booking a consultation with your GP or with a medical cannabis clinic to see if you might benefit from a medical cannabis prescription.