The Entourage Effect

The Entourage Effect and Terpenoid-Cannabinoid Synergy

As research delves into the uncapped potential of medical cannabis; a view of metabolite synergy offers indications of several highly promising lines of enquiry. 

Selective breeding and hybridisation are quickly resulting in the emergence of a variety of cultivars capable of producing highly desirable chemotypes.


The environment plants are grown in exert a high level of variability on the outcome produced by genes in the plant and the genome of the plant is extremely flexible in terms of its expression outcome. 


This is one of the many reasons why an isolated cannabinoid grown through yeast fermentation will have limitations, and will never compete with the full-spectrum gene expression produced by the cannabis plant.


The cannabis plant naturally produces a combination of phytochemicals in varied proportions, these rich phytochemicals produce a matrix of naturally occurring metabolites. The metabolites all work together in a variety of ways, an example of this would be the modulatory effects CBD has over THC.


By understanding the pharmacology of just two of these compounds we’ve seen dramatic results in a very short time. The success of GW Pharmaceuticals with the launch of their CBD-based treatments for Epilepsy - Sativex, and Exidiolex are examples of one of the many medical applications of cannabis.


To put the subsector into context - there are over 150 secondary metabolites produced by the cannabis plant including cannabinoids, terpenoids, sterols, and flavonoids. Each presents exciting possibilities for further research into endless therapeutic applications.


The Entourage Effect


Each metabolite compliments the other through a synergy known as the entourage effect. The entourage effect is the proposed mechanism through which each individual compound (other than THC) works to modulate psychoactive effects and offer greater overall therapeutic activity.


Cannabinoids have also been found to work well with other conventional medications - CDB’s ability to enhance the effects of antibiotics is an example of this. 


The synergy which takes place between naturally occurring compounds (which includes CBN and CBC) is unique and presents enormous therapeutic potential with a plethora of highly promising medical applications. 


Terpenoid-Cannabinoid Synergy


A second synergy also takes place when a full spectrum product is preserved, this time between exogenous and endogenous terpenoids produced by the plant. Terpenoids or ‘Terpenes’ also complement cannabinoid activity.


Terpenes are extremely volatile and degrade easily, a loss in the monoterpenoid content will likely detract from the therapeutic potential. Just like CBD they mitigate/eliminate the toxicity-associated effects of THC and contribute positively to the overall therapeutic experience.


Terpenes produce their own pharmacological effects - which is why in aromatherapy formulation we see the use of a number of terpenes that are also present in the cannabis plant.


Limonene for example is a very good mood-lifting agent and works well as an antidepressant. Linalool acts as an anti-anxiety agent in addition to reducing stress. Caryophyllene helps with pain and inflammation and Alpha Pinene is very good for a clear head and increased focus.

The knowledge we have of Terpenes and their therapeutic qualities can well be applied to achieve desired profiles and target a range of conditions. Further studies are now underway which aim to prove that the addition of certain terpenes improves the analgesic effect of THC.



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Image: The CBD Molecule - CBD's modulatory effects stand as evidence of cannabinoid synergy