Ever wondered why people say it’s better to buy whole plant CBD oil instead of CBD isolate? It’s all down to the entourage effect - the perfect synergy occurring between our bodies and the cannabis plant’s components; an effect that studies suggest potentiates the main active ingredients, reduces unwanted side effects and activates additional molecular pathways. But can we apply this principle to other areas of nutrition and herbal medicine?
What is the Entourage Effect?
First coined in the laboratories of Israeli scientist Raphael Mechoulam, the entourage effect refers to a cooperative synergy between all the compounds in the cannabis plant. We’re talking more than just the buddying up between THC and CBD, in which CBD reduces the psychoactive effect of THC and minimizes any memory impairment. No, here we’re dealing with something much harder to measure and define, where seemingly inert molecules such as minor cannabinoids, terpenes and flavonoids play an important role in creating the overall effect of the plant.
Chief Scientist at Americans For Safe Access explains: “When you’re throwing in a hundred or so compounds that are increasing and decreasing the speed of certain neurons, you definitely have a synergistic effect. And many of the compounds like the aromatics, the terpenes, the smell: they’re potent at ambient air levels, they can have an effect on physiology.”
Researchers have noted that whole plant cannabis or CBD oils have other benefits over isolated cannabinoids, such as giving a wider dosage window. In an Israeli study published in Pharmacology and Pharmacy, researchers noted that in trials carried out on pure CBD, “healing was only observed when CBD was given within a very limited dose range, whereas no beneficial effect was achieved at either lower or higher doses.”
Whole plant CBD extracts on the other hand showed a direct correlation between higher dosing levels and greater anti-inflammatory effects and pain relief, with no restrictive dosing window. Not only that but scientists found that less whole extract CBD was needed compared to the pure, synthetic variant, concluding: “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.”
But in the world of pharmaceutical research, where a single cause is viewed to exert a single effect, the entourage effect doesn’t find many advocates. Particularly when it comes to the cannabis plant and its dizzying array of over 400 molecules. So even in the laboratories of some of the most revered cannabinoid scientists, it’s single cannabinoids that are being studied for everything from cancer to neurodegenerative diseases. Hardly surprising when you consider most molecular biologists use a reductionist approach breaking down complex phenomenon into their most basic physical mechanisms and that no pharmaceutical company will invest millions of dollars in a plant that cannot be patented.
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Extending The Entourage Effect Beyond Cannabis
It’s easy to imagine how one could expand the entourage effect beyond cannabis to areas such as herbal medicine and nutrition in general. In the article ‘Beyond Synergy - the entourage effect in nutrition and herbalism,’ author Dallas Clouatre describes how in herbalism, it is generally agreed that whole plants give better results than high potency, isolated products.
He gives the example of Ma huang, a plant source of natural ephedra, which when combined with caffeine became a popular dieting supplement in the 1990s. Most ephedra on the market was synthetic in origin. However, this synthetic version caused hypertension in some cases and for that reason it was eventually banned. Interestingly, ephedra in its natural form did not cause these side effects.
“Why the difference?” asks Clouatre. “The answer,” he explains, “lay with the entourage effect — in Ma huang, there are a number of compounds that lower blood pressure and otherwise modulate the pressor effect of ephedra, thus making the plant source far safer than the synthetic pharmaceutical source of ephedra.”
He further extends the entourage theory to include the principles of Chinese and Tibetan medicine, where different herbs are combined to target a number of molecular pathways at the same time.
“Chinese herbs are not used singly in treatment,” he says, “but in combinations known as herbal formulas….Since a [sic] herbal combination has obvious advantages in treatment, the relationships between the herbs used in traditional Chinese medicine (TCM) have been carefully studied and certain types of relationship are identified. They are called the seven relations between herbs, e.g. mutual accentuation, mutual enhancement, mutual counteraction, mutual suppression, mutual antagonism, mutual incompatibility, and single effect.“
The Entourage Effect and Nutrition
Life would just be so easy if we could pop a few pills and satisfy our nutritional needs. But any nutritionist worth their salt will recommend that we should always try to get our vitamins and minerals from food.
If we all just lived on supplements, we would never thrive. That’s because, much like the cannabis plant, our sources of food contain a vast array of vitamins, minerals, phytonutrients, cofactors, and goodness knows what else. And these aren’t so haphazard as they sound. In the paper ‘Food synergy: an operational concept for understanding nutrition,’ we learn how the constituents in food are in in fact coordinated, whereby “the nutrient composition of naturally occurring food also reflects the biology of the organism.”
Take foods like nuts that are high in unsaturated fats; they come packed with antioxidants, which protect us against any cellular damage caused by the fats’ instability. Indeed, this synergy can be extended to all whole foods, so that “the action of the food matrix (the composite of naturally occurring food components) on human biological systems is greater than or different from the corresponding actions of the individual food components.”
Let’s take the humble orange: An average, medium-sized orange will supply approximately 70mg of vitamin C, which is not far off the recommended dose for a healthy adult. But when you eat your orange, you’re not just getting vitamin C - it also contains natural fibre, folate, B1, copper, potassium, calcium, the flavonoids hesperetin and naringenin, anthocyanins, hydroxycinnamic acids, and a variety of polyphenols. But it’s the flavonoid hesperetin, found in the peel and white pulp, that has drawn most interest. It has been found to lower blood pressure and cholesterol in animal studies.
Vitamin C is itself a much studied antioxidant, but when it comes to oranges, the fruit has its own unique mix that makes it a more effective source of antioxidants than vitamin C pills.
While most nutritionists talk in terms of food synergy in which the whole is greater than the sum of all the parts, we could also extend the entourage effect to the food we eat. Scientists still don’t know about every constituent in our food sources, and it’s quite possible that quite inactive molecules in food augment the nutritional benefits.
Nutritional Supplements, Herbal Remedies and the Entourage Effect
If you do decide to take a nutritional supplement or have been recommended an herbal remedy, it’s more important than ever to apply the principles of the entourage effect. Synthetic or isolated extracts do not match a supplement containing compounds as found in nature.
Dallas Clouatre advises caution when it comes to taking high potency herbs. “One of the dangers” he says, “is that the “guaranteed potency” that originally was meant to insure that the whole extraction was done properly has been deformed to reproduce the pharmaceutical model of pure substances and, as one consequence, leaving out important compounds found in the herbs and in the extracts as originally produced.“
That’s why, to benefit from the entourage effect, we always advise choosing a whole plant CBD oil above a high strength CBD isolate. And for a product with the most complete cannabinoid and terpene profile, we also recommend our Raw Hemp Oil range, which has not been through the decarboxylation process.