Research Review : Taming THC - by Dr. Ethan Russo

Today we will provide an overview of "Taming THC: potential cannabis synergy and phytocannabinoid-terpinoid entourage effects" which was published in the British Journal of Pharmacology by Dr. Ethan Russo. This has proven to be a groundbreaking and highly cited study, spawning new avenues of research and product development.

Dr. Ethan Russo, is a board-certified neurologist, psychopharmacology researcher, and former Senior Medical Advisor to GW Pharmaceuticals. He served as study physician to GW Pharmaceuticals for three Phase III clinical trials of Sativex (an oral THC spray). He was a clinical neurologist in Missoula, Montana for 20 years in a practice with a strong chronic pain component as well as working in Child and Adult Neurology at the University of Washington in Seattle.

THC has been the primary focus of Marijuana research since 1964, when THC was discovered and synthesized by Dr. Raphael Mechoulam. This review explores the terpenoids present in Medical Marijuana. Terpenoids are found all over in nature and are designated as GRAS (Generally Recognized as Safe) by the US Food and Drug Administration. Terpenoids by themselves are quite potent and have been shown to affect behavior in animal and human studies. Terpenoids have unique therapeutic effects (demonstrated by aroma-therapy) and may contribute to entourage effects in Medical Marijuana.

Often times Seniors using Medical Marijuana have reported that a specific strain seems to have better therapeutic effects for them than other strain varieties available. When compared, the two MMJ strains had similar cannabinoid profiles (cannabinoids such as THC and CBD) but had different therapeutic effects for the user. So if the difference is not in the THC or CBD content, it must lie in the “entourage” of other substances present in the plant in order to explain the difference perceived by various patients and Seniors.

Terepenes and cannabinoids (THC, CBD and others) are produced in the secretory cells inside the glandular trichome. Trichomes are the "frost" or "crystals" on the outside of your MMJ. Terpenoids, not cannabinoids are responsible for the aroma of Medical Marijuana.

Mice exposed to terpenoid odors from ambient air for 1 hour, "demonstrated profound effects on activity levels, suggesting a direct pharmacological effect on the brain, even at extremely low serum concentrations." Compelling confirmatory evidence in humans was provided in 1995, in a clinical study by Komori et al. Hospitalized, depressed patients were exposed to a citrus fragrance in ambient air. Using the Hamilton Depression Scores system, there was a "successful discontinuation of antidepressant medication in 9 of 12 patients.

- Limonene is common in lemons and other citrus essential oils, it is the second most widely distributed terpenoid in nature. If you've opened your jar of MMJ and swore you smelled lemons, its the limonene that you are smelling.

- Pinene is the most widely encountered terpenoid in nature. Most people love the fresh smell of Pine trees, that would be pinene. It also holds a variety of medical benefits.

- Myrcene is another common terpenoid in nature and Medical Marijuana. Through a variety of studies described in Taming THC, it is hypothesized that "myrcene is a prominent sedative terpenoid in cannabis, and combined with THC, may produce the couch-lock phenomenon" generally associated with Indica strains of MMJ.

While reading this study, we were astonished by the amount of positive information that supported the benefits of Marijuana as a medicine. With each medicinal claim, studies and dates are provided in the reference section. This provides transparency but given the publication source, we can be assured it was peer reviewed and vetted for accuracy. Regardless, many of these studies are 10 to 20 years old, which begs the question - why isn't this common knowledge? Dr. Russo’s study reports that cannabinoid-terpenoid interactions “could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal, and bacterial infections.”

Synergism may play a role in the widely held (but not experimentally based) view that in some cases plants are better drugs than the natural products isolated from them. An example provided in the study was the ability of CBD to reduce side effects of THC. It was shown that "CBD modulates the psychoactivity of THC and reduces its adverse event profile." This is one example of why whole plant medicine is so important and States that pass CBD only laws are misunderstanding the science.

Another connection of note published in this paper was "the ability of monoterpenoids to enhance skin permeability and entry of other drugs which may further enhance antibiotic benefits." This could be of large benefit when using topical applications.

The conclusion of the study can be summarized as : Selective breeding of Marijuana strains in regards to cannabinoid and terpene profiles can offer complimentary pharmacological activities that may strengthen and broaden clinical applications and improve the therapeutic index. Psychopharmalogical and dermatological indications show great promise.

Our conclusion is : There is a whole lot of science out there that supports the wide variety of benefits offered by the whole plant medicine of Marijuana. We also agree that terpene profiles provide distinctly different experiences and benefits. In our quest to understand more, we recently attended a Keynote speech by Dr. Ethan Russo covering his groundbreaking paper - Taming THC. Our review of that event will be available soon.

You can find the entire study for Taming THC, here.

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