Warning: Short, Technical, and No Worries if this Newsletter is not for you
but only for the True Cannabinoid Geeks

Dosing matters is obvious. Timing and mode of drug or supplement administration highly relevant. Even when and what you eat or drink makes a difference and can be problematic, positive, or neutral in terms of potential drug interactions.
With the increasing populations of new users of cannabinoids including older groups taking multiple prescription drugs, possible drug interactions, optimized timing of dosing, and other issues are being studied. This is a supremely complex topic and critical area of study so please read this newsletter in the spirit of general information, as opposed to broadly applicable scientific or medical concepts.

Of note is the fact that interactions between cannabinoids and other drugs, supplements and foods can be exploited to both increase the performance of the various molecules and substances as well as mitigate side effects and negative interactions.

Plenty of studies have been published regarding the in vitro and in vivo effects of cannabis and, THC and CBD in particular, on Cytochrome P450 (CYP or P450). More than half of all pharmaceuticals and many other substances are metabolized by this family of enzymes. You may have heard that if you take a statin to lower your cholesterol your doctor will tell you not to drink grapefruit juice ever again (grapefruit’s effect on metabolism can last several days).

To give you a deeper sense of the complexity of the science of understanding interactions, researchers are turning their attention beyond P450 enzymes to other enzymes involved in metabolism, including a major hepatic (aka the liver) esterase, Carboxylesterase 1 (CES1).

A published 2019 study by researchers at the University of Michigan and the University of Florida showed that large doses of cannabinoids can inhibit CES1 function, including THC, CBD and CBN. The study is important because CES1 is involved with activating or inactivating drugs that regulate blood pressure, including the ADHD drug Ritalin.

While the point of the study was to learn generally about problematic interactions of cannabinoids with the activity and role of CES1, the researchers point out that the major concern with potential cannabinoids interactions with other CES1 metabolized substances may be most relevant to high dosages of CBD isolate, as in really high dosages, compared to “normal” per serving and daily consumption amounts in health and wellness formulations.

CBN (and THC) are far less of a concern because they are typically consumed in single digit milligram amounts.

There is a comparatively much wider range of CBD dosages (per use and daily total consumption) and particularly when the approved CBD drug named Epidiolex is considered. Epidiolex is approved for certain severe pediatric epileptic indications. These child patients have highly compromised physiologies and they are prescribed doses into the thousands of milligrams of CBD per day.

In the researcher’s own words:”… the Ki (enzyme inhibitor) values suggest a clinically significant inhibition of CES1 by THC and CBD. CBN, however, is expected to have a limited impact on CES1. Carefully designed clinical studies are warranted to establish the clinical significance of these in vitro findings.”

The full details are in their published study, “In Vitro Inhibition of Carboxylesterase 1 by Major Cannabinoids and Selected Metabolites” which can be found at http://dmd.aspetjournals.org/content/47/5/465.

Our sole purpose in this newsletter is to showcase some high science, emphasis how complex physiology is, and highlight that more and more studies are being conducted and published about major and minor cannabinoids and their metabolites.

And if you haven’t figured out the punch line…

The potential of cannabinoids that have been used by humans for thousands of years are only now getting modern science’s attention with its modern tools. This is really exciting. And many lives will be greatly improved.

What Makes PPM Unique:

For minor and rare cannabinoids, including 100% hemp-derived CBN (100% THC-Free), we believe PPM is the only domestic producer of these naturally occurring minor cannabinoids selling kilo quantities consistently into highly demanding, large company supply chains.

PPM is led by a team of advanced-degreed scientists with pharmaceutical industry and university research backgrounds representing over 100 years of chemistry, food, natural products, and plant medicine experience.

PPM is committed to advancing the science and providing innovative true whole hemp plant extracts with fully customizable cannabinoid profiles, and minor and rare cannabinoid-based bulk ingredients, both 100% hemp-derived and biosynthesized from hemp plant precursors versions, including CBN, CBC, CBT, GBG, CBDA, THCV, and CBDV, to companies worldwide.

Clean. Consistent. Compliant.

Every day, every team member at PPM is inspired by the possibilities of plant-based medicine and remedies, and Mother Nature’s genius.

Krystle Jarrett
[email protected]