APR 04, 2019 5:18 PM PDT

The Entourage Effect - THC not TV

WRITTEN BY: Amy Loriaux

The cannabis plant has a myriad of compounds within it, all of which are taken into our bodies when it is smoked or eaten. Do these phytocannabinoids interact at all with each other? We have known that polydrug use can create metabolites that can alter their psychoactive effects. For example, cocaine and alcohol, taken together, produce cocaethylene, a metabolite produced in the liver that can enhance the effects of both substances, but which can also cause detrimental effects to the body after chronic exposure.

Photo source: PixaBay.com

So, it stands to hypothesize that marijuana, with all of its compounds (including our favorites THC and CBD), could react with each other to alter the effects of one on the effects of the other on the body and the brain. Dr. Ethan B Russo, in partnership with GW Pharmaceuticals in Britain, published a very extensive review of this synergy, or the pharmacological effects of one plant compound on the actions of another.

In cannabinoid research, this has been called the "entourage effect". According to Russo and many other prominent scientists in the field, these effects have been documented for CBD on THC, as well as the effects of terpenoids on THC. Terpenoids, as discussed previously in this newsletter, are produced by many plants, including cannabis, and are aromatic compounds that give plants their particular scent. Through a complex enzymatic process, terpenoids and CBDs produce synergistic effects which alter the pharmacology of THC.

For example, in 2006 Russo and colleagues discovered that CBD actually antagonizes (blocks) the effects of THC to some extent. This is important as more and more producers of cannabis are trying to increase the THC content while decreasing CBD. The interaction of terpenoids and THC has not been as well-studied, but from what work that has been done has produced evidence to support a synergistic effect of terpenoids on THC.

Photo source: UnSplash.com

What kind of actions are we talking about here? Well, on the whole, other phytocannabinoids, such as CBD or terpenoids could be an antidote for THC's psychoactive effects. According to Wagner and colleagues from the Ludwig-Maximilians-University in Germany, there are four mechanisms for synergy: (1) multi-target effects; (2) enhanced bioavailability; (3) Increased antibiotic properties; or (4) neutralization of adverse effects. In the case of CBD on THC, we would be talking about mechanism number 4. The effects of terpenoids on THC are less well-known, however, the terpenoid alpha-pinene is thought to counter THC's effect on cognition (working similar to acetylcholinesterase, the enzyme that degrades acetylcholine, inhibitors). So, again, we have an antagonist effect on part of THC's psychoactive effects.

Interestingly, these counteractive synergistic effects of other plant compounds have been known for centuries. Remedies for marijuana-induced acute psychosis were treated with lemon, calamus plant roots, pine nuts, and black pepper, to name a few. What do all of these remedies have in common? They all contain the same terpenoids that are present in cannabis. So if you find yourself experiencing marijuana-induced psychosis, go to the ER. These remedies may help, but I would rely on modern medicine in this case.

See the video below for more information on the evidence for and against the "entourage" effect. Remember folks, this is an early science, so some studies refute others. C'est la vie.

Video sourceYouTube.com

Sources: americanaddictioncenters.org, ResearchGate, European Journal of Pharmacology, LabRoots, Medical Hypotheses, Biological Psychiatry, British Journal of Pharmacology, Phytomedicine, Journal of Agriculture and Food Chemistry

About the Author
Doctorate (PhD)
I currently work at a small CRO involved in clinical trial management.
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