Entourage effect – Strength of cannabis plant extract

    27-Dec-2019
Dr Sona Pungavkar
Most people who are aware of medicinal Cannabis, have heard of the two most frequently heralded constituents of the plant extract, tetrahydrocannabidiol (THC) and cannabidiol (CBD). Although, these two names steal the thunder as far as medicinal Cannabis is concerned, many researchers emphasize that these can work better in conjunction with other constituents found in the plant. The other constituents include more than 100 compounds, mainly other cannabidiols such as tetrahydrocannabivarin (THCV), delta 1- tetrahydrocannabinolic acid (THCA), cannabigerol (CBG), cannabidivarin (CBDV),cannabichromene (CBC), cannabidiolic acid (CBDA) and terpenes such as limonene, myrcene, á-pinene, linalool, â-caryophyllene, caryophyllene oxide, nerolidol and phytol, and also flavonoids. Additionally, there are likely to be several undiscovered or unlabelled compounds within the plant, which also contribute to the highly acclaimed medicinal benefits of the miracle plant.
The effects experienced by a patient’s body when treated with medicinal Cannabis can be likened to a symphony. Although, each musician can generate music with his own instrument, only when they play in a certain rhythm, can awe-inspiring music be created. The combined effect of these musicians is the synergistic effect described in the context of the phytocannabinoids found in the Cannabis plant. Another simpler way to describe the effect is by using the analogy of making a meal. If one of the ingredients of the meal is omitted, it may not taste as good, though all the other ingredients listed in the recipe are present.
Shimo Ben-Shabat, an Israeli scientist, along with his team, concluded way back in 1998, that some endocannabinoids potentiated an expected effect via a different pathway, and helped in compounding the primary effect. He described this synergy as the entourage effect.
When all the constituents work in synergy in a patient, can maximum benefit of the plant be obtained.A single compound cannot produce the same effect as the entire phytocannabinoid army. Hence, there are many proponents of use of the full extract of the Cannabis plant rather than individual compoundsin isolation. It is important to understand this effect to direct formulation of products and treatment plans for appropriate use in precise medical research and as well as patient management.
Full spectrum preparations contain the entire gamut of the natural compounds found in the plant, including terpenes, flavonoids, and cannabinoids, thus allowing utilization of the natural expression of theplant’s chemotypeto exploit the complete entourage effect. Broad spectrum is the same as full spectrum, with omission of THC, providing partial or rather reduced entourage effect, as one of the main constituents is missing. Isolates contain only one specific cannabidiol, eg a THC isolate or CBD isolate.
Isolating active ingredient, while developing pharmaceuticals, has been practiced in common drugs such as aspirin and digitalis. Salicin is obtained from the bark of willow tree contains and is transformed into salicylic acid in the body. Digitalis is made in the same way from the Foxglove flower.
Pharmaceutical cannabis has taken a similar approach in the production of MarinolDronabinol, a synthetic THC isolate. Epidiolex,was also a synthetic pharmaceutical drug, containing, CBD isolate. These products did not achieve much popularity and were known to have side effects which were discouraging. This was attributed due to omission of the other ingredients and consequent loss of the entourage effect. Sativex, another pharmaceutical contains both THC and CBD, providing limited synergy.
There are plenty of studies which support supremacy of the full spectrum over the isolates or the broad spectrum preparations. Earliest reports were in the year 2011in British Journalof Pharmacology, when combination of cannabinoids and terpenes was thought to have better therapeutic results. Since then many such reports have been published.Biochemical Pharmacology, a reputed journal, recently published research documenting less antitumor activity with usage of  isolates,than full-spectrum or botanical preparations.
The entourage effect is unique for each strain of the Cannabis plant, with differences seen in the ratios of the constituents, mainly, cannabinoids, terpenes, and flavonoids. Hence, different strains would provide a variety of different synergies and each would have a different effect on the user. Let us look at a few synergies, which are known to science.
Cannabinoids interactions
The cannabinoidsis a group of active compounds, which can interact with receptors in thebody’s Endocannabinoid System (ECS)and provide beneficial effects. These are known to be commonly providing the entourage effect by working together either on the same pathway or by increasing the potency of the other compounds. For example, THC, CBD, CBC, CBG and CBN work together to reduce pain. CBD, CBC, CBG, CBN and THCV are known to reduce inflammation. Seizure control in epileptic patients has been attributed to the effects of THC, CBD, CBN and THCV, while THC, CBD, CBG, THCV, THCA, and CBDA are most likely possessing anti-tumor activity.
Phytocannabinoid-terpenoid interactions
Combined effects of the cannabinoids and terpeneshave alsobeen commonly researched and found to have interesting benefits.
Terpenes or terpenoidsare hydrocarbons, combination of hydrogen and carbon, also derived from the precursors of thecannabinoids. Each one of these has a unique flavour and smell. Terpenes bind with receptors and neurotransmitters in the body and brain, giving rise to specific effects, such as moodenhancement or providing energy boost.
Terpenes can be found in other plants, herbs and flowers such as in citrus fruits, lavender flower and pine trees. In the Cannabis plant, terpenes are found in the sticky resins and is associated with aromas produced by the cannabis plants.
These compounds stimulate the olfactory receptors in to manifest a variety of feel good effects.The benefits of the terpenes can be enjoyed in isolation or as part of the entourage effects. Linalool is known to reduce insomnia and anxiety, while anotherterpene called limonene reduces pain and inflammation.
All advocates of medicinal Cannabis need adequate knowledge of the entourage effect of the wonder drug leveraging it’s use, and contributing to good science.
We, at CHS, strongly believe that, Nature is wiser than all of humankind put together. What it has provided in terms of the Cannabis plant, is nothing short of a miracle.
Utilising it in it’s purest form, may be the best gift we can give to our patients.
The author is a Cannabis researcher, a senior radiologist and Vice President, Cannabis Health and Sciences