Recent guidance issued by the National Institute of Drug Abuse (NIDA) alongside other major organizations solidifies a foundation for cannabis research standards and protocols. Here’s a brief intersection on how the current pharmaceutical industry operates to better understanding what layers need to be peeled back in streamlining the cannabis conversation into modern medical relevance.
Years prior to a (usually) single-molecule prescription drug coming to market, a pharmaceutical manufacturer begins the complicated process of filing an Investigational New Drug (IND) application with the FDA prior to human clinical trials. Within the IND application, various items are presented including animal study data/toxicity, manufacturing information, and clinical study designs. Based on this information, a drug dosage is established by the pharmaceutical manufacturer with a specific therapeutic outcome. When you go to the pharmacy and fill a prescription for something like an antibiotic, a dosage form and course of therapy are clearly dictated by the physician, and transcribed by the pharmacist, e.g.”One 500mg capsule twice a day for 10 days”. This standardized therapy protocol is driven by years of research and multitudes of data points gathered from these large clinical trials.
Cannabis research has been restricted by lack of access and intense procedural hurdles of studying drugs with a Schedule I designation. Until very recently (last week), cannabis was only available for research from ONE source: the University of Mississippi, and reports have been generated questioning the quality/potency being sub-par and not in line with the cannabis consumed by patients in current medical programs. Independent institutions have also cited fears of losing federal research grant funds, again simply because of the Schedule I designation that cannabis holds. As cannabis becomes more widely recognized as a generally-safe and effective alternative/adjunct to prescription drugs, more plentiful research opportunities have begun presenting itself.
Whether it be hemp, marijuana, or cannabis, the name is referring to a physical plant. The sticky, resinous glands on top of female flowering plants (trichomes) contain inert pharmaceutical components (phytocannabinoids). Tetrahydrocannabinolic acid (THCa) and cannabidiolic acid (CBDa) have been efficiently cultivated through highly tailored practices, but are only two out of hundreds of other constituents that may be contained on one cannabis plant. Comparing single-molecule pharmaceutical ingredients to the broad term of “cannabis” is more akin to comparing apples to an apple orchard.
“Comparing single-molecule pharmaceutical ingredients to the broad term of ‘cannabis’ is more akin to comparing apples to an apple orchard.”
The next step in activating these phytocannabinoids is removing the acidic component through decarboxylation (usually by heat), yielding the active counterparts of THC and CBD respectively. Now that 5mg of THC is defined as a standard unit, research has a centralized focal point to begin. What are some of the next hurdles that must be addressed?
- How do we accurately calculate the amount of mg of THC from dried flower products?
Manufactured products liked edibles and lozenges contain labels expressing quantities of phytocannabinoids like THC in milligrams (mg) which is a measurement of weight i.e. how much total THC is in this product. Labels for dried flower products express quantities in percentages, a measurement of volume i.e. how much of this total product is made up of THC.
A standards dose of 5mg of THC is easily measurable in manufactured products or can be simply calculated in tinctures. What happens when you have a jar of dried flower containing a label with % of THCa as well as THC? How much dried flower does a patient need to consume to yield a standard dose of 5mg THC? Websites offering calculations like these and these, cite a 0.877 conversion rate based on the difference in molecular weight of THC vs THCa. Have any current pharmacokinetic data studies been conducted to support this theoretical basis? What effect do minor cannabinoids and terpenes play in while consuming whole plant material? Studying the apple orchard is extremely more complex than studying one apple at a time.
- What temperature and duration of time is ideal for decarboxylation?
If you ask 3 people experienced in making cannabis edibles for their step-by-step guide, you very well might receive 3 different answers about what temperature and amount of time they use during the decarboxylation process. For consumers using dry-herb vaporizers, devices can be programmed to ranges between 310°F to 450°F, manifesting different user experiences based on the temperature. Boiling points of terpenes are neatly laid out in charts, but how does that translate to a “standard dose” and what temperature and duration of time can be used as a standard for decarboxylation to yield desired results?
- What is the ideal length of “one inhalation”?
For asthmatic patients using a rescue inhaler like albuterol, the medication comes as a metered dose inhaled (MDI). Each depression of the device yields the same amount of medication every single time, leading to consistent, replicable, and predictable results. When combusting or vaporizing cannabis, the length of inhalation will alter the amount of phytocannabinoids entering the blood stream via pulmonary pathway. Is a 3 second inhalation universally recognized as a standard dose?
Progress is progress. For every foundational layer set, more questions will arise. Uniformly recognized data and standards will build credibility to research protocols for the future and also allow the medical cannabis industry to gravitate towards more recognizable pharmaceutical standards, building confidence levels and a sense of familiarity between clinicians and patients alike. As always, let’s continue the conversation.
-Alan