The Bioavailability of Cannabidiol

Of all the cannabinoids derived from the Cannabis sativa plant, only cannabinol has been extensively studied, approved for regulated use in humans, and considered a potential alternative therapy for the management of numerous conditions. As expected of any substance of biological importance to man, a pure CBD isolate is analyzed and examined for physio-chemical properties for dosage recommendations and toxicity studies. Physio-chemical properties determined in processes of drug analysis include solubility, passive permeability, bioavailability, protein binding, isomerism, the dissociation constant, and complexation.

Bioavailability is a parameter that expresses the extent to which the active form of an administered drug enters systemic circulation and reaches the target site to effect the desired action. In some literature, this term also describes the proportion of the drug that reaches the target site. The values of this property have been found to depend on the route of drug administration, dosage form, drug metabolism rate, food intake, and blood circulation. In essence, the dosage form of CBD extensively affects its bioavailability rate. Since the legalization of CBD use in human medicine, production companies have developed different presentation forms for this constituent of the Cannabis sativa. 

In a bid to satisfy increasing demand, CBD is now produced as tinctures, edibles, gelatin capsules, vape oils, and cream. In cases where pure, concentrated forms of the substance are desired for maximal effect, the forms of CBD preferred include concentrates, extracts, aerosol sprays, and solvent isolates. Gel, transdermal patch, chewing gum, and suppository forms are also available for special population demography, especially in geriatrics. It is, however, important to state that the bioavailability of CBD presented in these forms varies. 

The bioavailability of different forms of CBD

Much of what is known about the properties of cannabinoids generally are based on anecdotal pieces of evidence with little or no scientific support. Numerous funded studies have been undertaken in an attempt to develop standard reference values for the bioavailability of CBD form.

• Cannabidiol capsules

Cannabinol capsules are administered orally. The capsules follow through the gastrointestinal tract, where it is absorbed and metabolized by the liver. Metabolism can also occur in other parts of the body, including the lungs. In all oral forms of drug presentation, the bioavailability is reduced when compared with other forms. In humans, the bioavailability of CBD capsules is reduced by the first-pass effect. This describes a phenomenon by which a drug is metabolized at specific locations in the body leading to a reduced concentration of the blood in the systemic circulation. 

With the first-pass effect on CBD, the amount of active moiety that reaches the active site through the bloodstream is reduced. In 2012, a randomized, double-blind clinical trial was conducted to evaluate the acute effects of cannabinoids administered orally in healthy volunteers. As reported by the Journal of Current Pharmaceutical Design, the acute effects observed in the subjects were based on the amount of cannabinoid administered—bioavailability increased with an increased quantity of oral dosage administered. In a 2018 publication, the Journal of Perioperative Medicine reported the bioavailability of oral CBD to be within the range of 2 to 20 percent.

• Intravenous CBD

The injectable forms of CBD are reserved for medical use only. In the management of neuropathic pain, seizure, and multiple sclerosis, intravenous CBD is administered directly into the bloodstream as an alternative therapy approach. The first pass effect does not reduce the bioavailability of this form of CBD. The bioavailability of intravenous CBD is at 100 percent, just as in other injectable pharmaceutical products. However, the half-life is short at 24 hours. 

• Inhaled CBD

The inhaled form of cannabidiol is perhaps the most popular present form, especially in regions where recreational use of the product is allowed. CBD can be inhaled by nebulizing, vaping, and smoking. Vaping and nebulizing are specially used in geriatric care centers. In all these forms, the half-life of CBD averages about 31 hours. Inhalation is an efficient method of attaining a relatively high concentration of CBD at the active sites as the product bypasses the sites of the first-pass metabolism. Researchers have determined the bioavailability of inhaled CBD to range from 10 to 35 percent. 

• Sublingual CBD

Sublingual administration involves placing liquid formulations of CBD under the tongue for direct absorption into the minute blood vessels lining the membrane of the mouth. With this method, peak blood concentration is achieved in about two hours. The first pass effect is when CBD is administered through this route. The bioavailability of CBD through this route is in a close range to that in the inhalation route. 

Measuring the bioavailability of CBD

Bioavailability measurements are generally determined in a designed clinical inquiry that might require professional expertise in the pharmacological sciences. To assess the bioavailability of a CBD form, healthy volunteers or long-term users of CBD are required to use a specified quantity of the product under medical supervision. The normal processes of absorption, distribution, metabolism, and elimination occur in these subjects. Under expert supervision, blood samples are then taken from these subjects at a specified time interval and analyzed for CBD content. 

The concentration of CBD in the blood varies with time. Concentration is maximum at a peak level when the rate of drug absorption equals the elimination rate. Using the data gathered a graphical representation depicting the relationship between time and plasma concentration of CBD. The bioavailability of CBD is then assessed by determining the area under the concentration-time curve (AUC). AUC is in a direct proportion to the total amount of unchanged drug in the systemic circulation and is regarded as the most reliable index to determine the bioavailability of a drug product. An alternative method of estimating bioavailability involves measuring the total amount of unchanged CBD excreted through the urine after a single CBD dose administration. Multiple dosing is required to determine CBD concentration over 7 – 10 elimination half-lives. Bioavailability is then determined by measuring the amount of unchanged CBD in urine over a 24-hour period. 

REFERENCES

• https://link.springer.com/article/10.1186/s13741-019-0127-x
• https://www.ncbi.nlm.nih.gov/books/NBK551679/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689518/#!po=30.6818
• https://www.msdmanuals.com/professional/clinical-pharmacology/pharmacokinetics/drug-bioavailability
• https://www.researchgate.net/publication/329183487_A_Systematic_Review_on_the_Pharmacokinetics_of_cannabidiol_in_Humans