Why the “ensemble effect” is interesting for the hemp business

Therapeutic hemp flowers have a tremendous therapeutic effect when used both as food (salad greens, seasonings, etc.) and with minimal processing as various kinds of additives, drinks (teas, non-alcoholic, low-alcoholic), cosmetic products. Given the fact that a number of varieties have already been bred and entered into the state register in the country, the leaves and inflorescences of which have a huge therapeutic effect, there is little left to do - to regulate the legality of their use on the territory of our country.

The ensemble effect is a hypothesis that was first proposed in the early 2000s and was based on the idea that consuming a whole plant may be more effective than taking a drug based on only one of the active components of the plant. 

The hypothesis has been rechecked many times since it was first expressed. Today, a significant part of scientists argue that different varieties of the hemp plant may be more effective for certain disease states or localization of symptoms of various kinds of discomfort, depending on their chemical profile.  

What is "ensemble effect"

The vast majority of prescription drugs in the economically developed countries of the world are based on the use of the therapeutic properties of a single molecule. There are several drugs approved by the relevant government agencies in several countries, the therapeutic effect of which is based on the work of two main hemp molecules - tetrahydrocannabinol (THC / THC) and cannabidiol (CBD / CBD). However, it must be borne in mind that hemp contains hundreds of natural compounds with tremendous therapeutic potential. 

In 1999, Israeli researchers Shimon Ben Shabat and Rafael Meshulam first raised the question of a mechanism according to which the therapeutic effect of a hemp plant can significantly exceed the work of pharmaceuticals. At that time, it was suggested that the more powerful therapeutic properties of the plant itself are due to the mutual enhancement of the therapeutic effects of the compounds included in it. This hypothesis was based on the data of the above-mentioned scientists, obtained by them in the course of studies of the endocannabinoid system of the human body, but not of the hemp plant itself. 

The researchers drew attention to the fact that certain endocannabinoids, produced naturally in the body, are more effective when delivered with other, inactive compounds. Or, according to scientists, "Biologically active natural products ... in many cases are accompanied by chemically bound, albeit biologically inactive, constituents ... Studies of the action of an active ingredient in the presence of its" surrounding "compounds can lead to results that are positively different from those observed only with the active component ". 

Based on their studies, Israeli scientists concluded that "this type of synergy may play a role in the widespread view that in a significant number of cases, the plants themselves are better medicines than the extracts obtained from them." 

Several years later, researcher Elizabeth Williamson presented a proof-of-concept that "a fully or partially purified plant extract has clear advantages over a single isolated ingredient in cannabis." 

One of the currently well-known examples indicated the ability of CBD to attenuate certain side effects of THC. Ms Williamson concluded from an in-depth study of this issue that "this synergistic effect will be very important if cannabis becomes a drug, reducing the often unwanted psychotropic side effects."   

How the "ensemble effect" works

Despite the fact that a number of researchers have contributed to the theory of the environmental effect in relation to cannabis, the person most deeply studied this issue is Dr. Ethan Russo. In his 2011 article “Taming THC: Potential Cannabis Synergy and Phytocannabinoid-Terpenoid Effects of Entourage” I. Russo described in detail previous works on cannabinoid synergy, introduced the term “entourage / ensemble effect”, and also defined its mechanism of work. 

To explain how the “ensemble effect” works, Dr. Russo, in the above article, cited a study from Germany in 2009 that identified how herbal synergy works in general, not just cannabis. It describes four main mechanisms, three of which are particularly relevant to the hemp plant (described below). 

1.  Effects of enhancing multiple targets

Most often, pharmacological drugs act on one or two molecular targets in our body, creating a certain effect. The multipurpose effect means that plant compounds can act for many purposes. In cannabis, a popular example is the interaction of cannabinoids with CB1, CB2, GPR18, GPR55, TRPV2, TRPV3 and many other receptors. These multiple targets multiply the effects of cannabinoids.

But it's not just about cannabinoids, terpenes and flavonoids have significant therapeutic effects, which can also potentially activate multiple targets, thereby enhancing or modulating the effects of cannabinoids.

One of the first published examples of the potentiating effects of a particular cannabinoid when administered synergistically was the comparison of a pure preparation containing exclusively the aforementioned therapeutically active element with a whole plant extract in the treatment of spasticity. At equal doses of the same cannabinoid, whole plant extraction was considered "significantly more effective in antispasticity than cannabinoid alone." 

2. Effects of enhancing molecular motion

The two main divisions of pharmacology are pharmacodynamics (how drugs affect your body) and pharmacokinetics (how your body affects drugs or the movement of drugs in the body). While the multi-target enhancing effects of cannabis are related to pharmacodynamics, the plant's effects on enhancing the movement of therapeutically active elements in the body are related to pharmacokinetics. 

The result is similar (enhanced effect of cannabinoids), but the method is slightly different. The multi-target amplification effect is caused by the interaction of molecules with multiple targets. Whereas the effect of enhancing the movement of a whole cannabis plant is due to the fact that a group of molecules (entourage / ensemble) moves in the body more efficiently than if one of them was traveling alone. 

Terpenes, in particular limonene, alpha-humulene, linalool, beta-pinene and pinene, are one example of the effects of enhancing molecular movement. These therapeutically active elements of the hemp plant are biologically active and can induce relaxation of the lungs and airways, but when taken by themselves may not cause a serious reaction in the body. However, when terpenes work in conjunction with cannabinoids, for example, absorption of cannabinoids through the lungs can be improved by the presence of these bronchodilating terpenes. 

3. Modulation of side effects

These effects "can be achieved when the component contained in the plant extract" neutralizes "or destroys the toxic active component and therefore provides better efficacy compared to the original crude drug."

Some of the side effects of cannabis are related to THC, and while there are several plant compounds that can help counteract these side effects, the best and most popular natural remedy is CBD.

A growing body of research confirms the ability of cannabidiol to reduce the side effects of THC, especially memory impairment, anxiety, and psychotomimetic effects (such as paranoia and social isolation). 

Terpenes and cannabinoids - the hemp environment effect

In “taming the negative effects of THC on the body,” Dr. Russo also added a new line of research: perhaps it is not only the interaction of THC and CBD, but other plant compounds such as minor cannabinoids, terpenes and flavonoids that play a role in the environmental effect.

Terpenes are aromatic molecules responsible for the smell and taste of most plants, but they are also pharmacologically active and can affect the body. One of the unique characteristics of the hemp plant is the variability in terpene content (there are almost 200 different terpenes in hemp). 

According to Dr. Russo, the abundant terpenes in a given chemical variation (chemovar) of a plant can determine its effects. These terpenes can influence whether the plant's effect is calming or stimulating, and whether it is better for conditions and symptoms such as pain, inflammation, anxiety, epilepsy, or depression. 

Some examples of the potential synergy between cannabinoids and terpenoids suggested by Dr. Russo include: 

•  anxiolytic (CBD + linalool and / or limonene);

•  anticonvulsant (CBD + linalool);

•  immunostimulant (CBD + limonene)

•  anti-inflammatory (CBD + pinene);

•  pain reliever (CBD + linalool).

•  bronchodilator (THC + pinene);

•  Alzegimer (THC + limonene, pinene or linalool);

•  muscle relaxant (THC + linalool and / or myrcene);

While there is evidence of synergy between cannabinoids (mainly THC and CBD), the synergy of terpenoids and cannabinoids, as logical as it may be, is currently supported by only a small amount of experimental evidence.

How the “ensemble effect” can change modern cannabis production

Assuming that the environmental effect is correct, and that cannabinoids and terpenes can interact with each other and play a role in how different types of cannabis affect the body, there could be practical implications for researchers, consumers, healthcare professionals, growers and consumers. ...

What does “ensemble effect” mean for agricultural producers and processors

The “ensemble effect” can have a significant impact on cannabis cultivation, as this trend of modern cannabis production will have to evolve rapidly in order to meet future market demands. Currently, most Hemovars only contain cannabinoids with various terpenes (mainly myrcene or beta-caryophyllene). Consumers will eventually look for cannabis varieties with a more diverse chemical profile in order to better exploit the ambience effect. Therefore, in the near future there will be a need not only for CBD or other drug-free cannabinoids, but also for a wide variety of terpenes. With regard to production, more detailed labeling will be required, which will represent not only the concentration of cannabinoids, but also other therapeutically active elements in the plant, in particular terpenes.

What does entourage effect mean for consumers?

One of the main consequences of the environmental effect for consumers will be which varieties of plants perform more effectively and, accordingly, who and why chooses certain hemp products. If the profiles of the cannabinoids and terpenoids of cannabis plants determine their effects, some system will be needed to categorize and group these products.

In an ideal world, after a lot of research into the “entourage effect” has been done, hemp products could be grouped together to use and treat conditions and symptoms such as pain, sleep, nausea, headaches, or cramps. They can also be categorized as daytime or nighttime, as well as evening products, more suitable for a relaxing time, partying or work. 

Commentary of the specialists of the Association "Ukrainian technical hemp"

There is overwhelming evidence that a variety of terpenes increase the activity of cannabinoids, thereby enhancing their therapeutic properties. In a number of economically developed countries of the world, there are already statistical indicators of how many pharmacological preparations based on the therapeutic properties of cannabis cause side effects, which are often more than the positive result obtained from their use. 

There are national studies and developments in this area that indicate that therapeutic hemp flowers have a huge therapeutic effect when used both as food (salad greens, spices, etc.) and with minimal processing. as various kinds of additives, drinks (teas, non-alcoholic, low-alcohol), cosmetic products. Given the fact that a number of varieties have already been bred and entered into the state register in the country, the leaves and inflorescences of which have a huge therapeutic effect, there is little left to do - to regulate the legality of their use on the territory of our country.