3. The role of biological variability in Cannabis dosing
This is Part 3 in a 5-part series on Dosing & Administration: What is the correct dose of THC or CBD to relieve symptoms and treat various medical conditions? It depends on a variety of factors.
(You can learn more about factors that influence dosing and administration here).
One of the most important factors is the degree to which these cannabinoids, and other compounds, are absorbed into the bloodstream. Bioavailability (Similar to absorption) is one of the key elements of pharmacokinetics. Pharmacokinetics is a pharmacology term that refers to how the body processes drugs.
There are four essential components to pharmacokinetics: Absorption of the drug, metabolism of it, and distribution within, and elimination from, the body. The focus of this article is the absorption of THC and CBD, and understanding how the dose administered can be very different from the dose that is received.
Absorption of cannabinoids
Let’s say that ten individuals each eat a cookie infused with 10mg of THC. The concentration of THC is then measured in their blood over time. Will the concentration of THC, and its metabolites, be the same in each individual at each point in time? No, of course not. It is highly likely that each person will absorb a different amount. Will the difference between the highest concentration in one individual and lowest concentration in another be small? Probably not.
There are many reasons why this may be the case. Perhaps some of these individuals consume the cookie on an empty stomach. Perhaps some of them have medical conditions that influence the absorption of nutrients in their small intestine. Perhaps there are structural differences or physiologic factors that influence the transit time of nutrients thru their gastrointestinal tract. There are many other possible explanations. We are biologically diverse creatures.
Pharmacokinetic studies Researchers engage in pharmacokinetic studies to better understand these dynamics. A study published in 2005 provides some insight into the pharmacokinetics of THC and CBD.1
Plasma concentrations of THC, and its metabolites, and CBD were measured in twenty-four healthy volunteers after a single oral administration of a capsule containing 10 mg of THC and 5.4 mg of CBD. Among other things, the maximum concentration (Cmax) and the time required to reach the maximum concentration (Tmax) were measured at various points in time for each these biomarkers .
In common parlance, delta-9-THC is simply referred to as “THC”. In addition to THC, there are two main metabolites which are typically measured and graphed in studies of this type: 11-OH-THC and THC-COOH (i.e. 11-nor-9-OOH-THC). THC is first converted to 11-OH-THC, which is then converted to THC-COOH (See below).
It should be noted that there are more than 100 metabolites of CBD as well. We don’t know as much about their biological activity, however.
The two graphs below depict the plasma concentration curves of two different volunteers in this study - Volunteers 846 and 835 (See Figure 1).
Figure 1.
Let’s look at some of the differences.
For starters, look at the difference in the maximum concentration of THC in Volunteer 846 (~10 ng/ml) as compared to Volunteer 835 (~2.5 ng/ml). That's a 300% difference (4 times). Is that difference enough to affect the volunteer's subjective experience? Yes, of course. Volunteer 846 may be severely impaired while volunteer 835 may not feel impaired at all. The same may be true for any change in symptoms.
To be clear, both of these individuals were given the same dose, but one registered a maximum concentration that was 4 times greater than the other. As a healthcare provider, how am I supposed to know which of these is my patient? As an individual experimenting with Cannabis-infused edibles, how are you supposed to know how much THC or CBD you are going to absorb?
Inhalation versus ingestion
It should be pointed out that the pharmacokinetic graphs are different for ingested Cannabis as compared to inhaled Cannabis. Thus the method of administration is a very important consideration when trying to determine the appropriate dose.
(You can learn more about the pharmacokinetic differences between ingestion and inhalation here)
Let’s turn our attention to 11-OH-THC, a metabolite of THC. Look at the difference in the maximum concentration of 11-OH-THC in Volunteer 846 (>12 ng/ml) as compared to Volunteer 837 (>3 ng/ml). Again a 4x difference. Also, levels of 11-OH-THC are higher than the THC levels in three of the four volunteers (See Figure 2).
Figure 2.
Why is this important?
Because 11-OH-THC is up to 7x more potent than THC. It has a much greater affinity for the cannabinoid receptor (CB1).2 It also crosses the blood-brain barrier more easily than THC. This may explain why ingested cannabis products are often much more potent than inhaled cannabis products.
A few final points on pharmacokinetics from this study. First, this study also compared a THC-only capsule (With the same dose, 10 mg) to the THC and CBD capsule (10 mg of THC and 5.4 mg of CBD) discussed above, in the same volunteers. When CBD was included in the capsule, it increased the bioavailability of THC by 27% and 11-OH-THC by 9%. This means that the dose received may also vary based on the other ingredients.
(You can learn more about the pharmacokinetic differences between ingestion and inhalation here)
The bottom line When it comes to how the body processes drugs (i.e., Pharmacokinetics), there are significant differences across human beings. People process drugs differently. Very differently. This is clearly demonstrated by the bioavailability of cannabinoids in the gastrointestinal tract. The appropriate dose of THC or CBD depends on an individual’s personal pharmacokinetics, among other things. The dose administered may be vastly different from the dose received. In addition, the dose received by one individual may be vastly different than the dose received by another, despite the fact that both were administered the same starting dose!
In health,
Despite the favorable safety profile, dosing and administration of cannabinoids is complicated. The process should be highly individualized and is best supervised by a trained health care professional. For more information, please consider booking a consultation (telephone or in-person) with Dr. Jamie Corroon, ND, MPH.
References
1. Nadulski T, Sporkert F, Schnelle M, et al. Simultaneous and sensitive analysis of THC, 11-OH-THC, THC-COOH, CBD, and CBN by GC-MS in plasma after oral application of small doses of THC and cannabis extract. Journal of analytical toxicology. 2005;29(8):782-789. 2. @sapiensoupblog. Human Metabolism of THC. In: @sapiensoupblog; 2016.
