| Blood and Guts Metabolism is a broad term encompassing a wide range of biochemical processes in your body. Your metabolism can be considered a gatekeeper of molecules seeking admittance to your bloodstream. But let’s talk about your gut that processes incoming molecules alone or with other compounds arriving for processing at the same time – whatever else you ate or drank or smoked recently. A key system of the gut is your liver – a super-smart organ, efficient, and always on the job – which continually processes a gallon of blood every two and a half minutes. It is a filter, a detoxifier, and an enzyme manufacturer. It is impressive at doing its job. Your liver makes judgments about what immediately gets excreted from the body and what gets metabolized. First pass metabolism is critical, as is second pass, i.e., the second time a substance passes through the liver in the bloodstream as it cycles. Notably, compounds are routinely, consistently transformed into other compounds during these trips through the liver and gastrointestinal system. Some cannabinoids are converted into other bioactive or non-bioactive metabolites, including non-naturally occurring cannabinoid family chemical compounds. The human liver does not make it easy for cannabinoids to access to your endocannabinoid system (ECS) receptors. The fact that cannabinoids appear to have high absorption variability adds to the complexity of determining “typical” pharmacokinetic (PK) and pharmacodynamic (PD) curves. For example, acidic forms of cannabinoids have been shown to have naturally higher bioavailability due to the pH dependence of lipophilicity. This means cannabidiolic acid (CBDA) will have a higher bioavailability compared to cannabidiol (CBD). All of these factors require further study. Differences in PK and PD curves can vary greatly between a plain cannabinoid molecule and one that has been supercharged with an enhanced drug delivery system that is common technology in the pharma and functional food world and whatever else is in your system or on its way in. It is a complex equation with many, many variables, and each of us is different. The tried and true maxims of “low and slow”, “consult with your doctor”, and “one size doesn’t fit all” surely apply with anything you add to your individual physiological equation at a particular time. One of the primary goals of Precision Plant Molecules science-driven approach is to produce uniform, standardized, non-psychotropic cannabinoid bulk ingredients for precision formulations and to enrich plant extracts to have specific and standardized phytocompound profiles. Such uniformity allows a consumer, and their doctor, to have the basic quantitative information to evaluate the appropriate amount to take, when to take it, what interactions to be mindful of, daily maximum dosing, and other factors including the consumer’s medical conditions and history. The current “hit or miss” or “self-dosing” situation with most cannabinoid consumer products is not an acceptable approach. More human studies will help in determining PK and PD curves for cannabinoids formulated in different consumer products via their different form factors and delivery modes. In the near term, more detailed and quantitative product labeling will greatly help. Only with accurate product labeling that specifies the number of milligrams of a phytocannabinoid in a serving or dose can an informed decision be made. Hopefully, sooner rather than later, consumers will be able to choose products with a label that specifies a serving or recommended dosage, e.g.) 30 mg of CBD, 20 mg of CBC (cannabichromene) and 10 mg of CBG (cannabigerol) in a Gummy Bear. Or maybe a soft-gel with 10 mg of THCV (tetrahydrocannabivarin) and 10 mg of CBD for a calm but focusing boost. Or a sleepy time lozenge with 5 mg each of melatonin, CBD and CBN (cannabinol). More effective and more personalized remedies and medicines are the goal. PK and PD curves, enhanced delivery technologies, and detailed, quantified cannabinoid product labeling, together with more research, will allow cannabinoids to achieve their full potential. | 
