Science Digest – Has the quest for the Entourage Effect only just begun?

    Currently, it is widely accepted by the scientific community that cannabis contains substances that interact with each other to produce a combined effect greater than their individual effects put together, known as the Entourage Effect. 

    For those who believe that in some cases, plants can be better drugs than the isolated active ingredients alone, the existence of the Entourage Effect is only logical and would explain many of the claims from cannabis users.

    There is some scientific evidence to support this theory, although everyone wishes there would be more. First, there is a strong need to clarify beyond any doubt that the Entourage Effect is real. Then, there are still a lot of questions to be answered:

    • Which and how many phytocannabinoids interact to produce better results?
    • What is the nature of this interaction? What mechanisms are involved?
    • Do you always get ‘a better response’ with the same combination in different scenarios?

    I could go on for a while.

    What about interaction with other substances from the same plant, such as terpenoids? 

    Terpenoids are the chemical substances responsible for taste and smell in our food. Examples of the most common terpenoids found in cannabis are:

    • Limonene (also found in lemons)
    • a-Pinene (also found in pine)
    • Linalool (also found in lavender)

    These are easily recognisable and are famous for their unique effects (e.g. lavender helps to relax). So, it is only natural that scientists want to know if the Entourage Effect also includes interactions between phytocannabinoids and terpenoids. The search for proof that the Entourage Effect exists between phytocannabinoids and terpenoids has begun only very recently, but some results are in.

    One, in particular, immediately caught my attention: “Absence of Entourage: Terpenoids Commonly Found in Cannabis sativa Do Not Modulate the Functional Activity of D9 -THC at Human CB1 and CB2 Receptors“. If you are a supporter of the Entourage Effect, this title will make your heart jump. My first thought was that someone found proof that the Entourage Effect is a fabrication or wishful thinking. I would be disappointed, but accept it and work with the new information going forward.

    However, let’s not jump into conclusions and take a good look at what these scientists are REALLY saying. The title says that (read the words in bold) “Terpenoids Commonly Found in Cannabis sativa Do Not Modulate the Functional Activity of D9 –THC at Human CB1 and CB2 Receptors.” Now I understand that the terpenoids tested do not interfere (absence of Entourage) with how THC activates the human cannabinoid receptors. 

    Here’s what they did:

    • They took mouse pituitary gland neoplasms cells, and to some, the scientists added the human version of the cannabinoid receptors. This way, if any effect is measured, they can be confident in saying that the effect of the terpenoids was caused at the receptor level. 
    • First, they tested if by adding terpenoids to the liquid that surrounds the cells, which mimics the space between them, would cause a response in these cells, without the cannabinoid receptors. Result: No effect.  
    • Now they are confident they can use this model to study any change in the activation of the human cannabinoid receptors introduced in these cells. They added the same terpenoids to these cells and measured their response. Result: No effect. 
    • To determine if terpenoids interfered with the activation of human CB1 or CB2 receptor they added to the liquid a synthetic cannabinoid, known to activate either of these receptors. Result: No effect.
    • Then they proceeded to repeat the tests above with THC, using different combinations of concentrations of THC and terpenoids. Result: No effect.
    • They even tested a solution with all six terpenoids together on the activation of the human cannabinoid receptors by THC. Result: No effect.
    • Lastly, the scientists tested if terpenoids would desensitise the human cannabinoid receptors, an effect generated by other cannabinoids. Result: No effect.

    From the above results, the only possible conclusion is that no Entourage Effect is observed in this particular model, with these specific terpenes. 

    However, if we deduce anything else from this study, then that is all we are doing: deducing. In fact, the scientists highlight in the limitations of the study that there are many other ways in which terpenoids could interact with THC, and they finish this publication by saying that “the quest for entourage does not end here; in many ways, it has only just begun“.



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