Pharmacokinetics

CBD oil, a common formulation, is a concentrated extract dissolved in an edible oil.27 The use of solvents to extract the CBD varies among producers and can affect color, taste, and viscosity. Oil is favored among consumers due to the ease of ingestion, ability to receive high concentrated dosing, and avoidance of stigma that may be associated with smoking or vaping.27 However, CBD oil is poorly absorbed in the gastrointestinal tract, and oral bioavailability of CBD oil has been estimated at 6%.28 Aerosolized CBD has greater bioavailability than oral administration and rapid peak plasma concentrations.28

CBD is primarily metabolized through the liver; the 2 main cytochrome pathways involved are CYP3A4 and CYP2D6.29 More drugs are metabolized via CYP3A than any other P450 enzyme.30 The effects of CBD dose and absorption on drug-drug interaction requires further research.

Safety

CBD consumption is not associated with risk of intoxication.31 Due to scarce clinical evidence, the available data on proper dosage, drug-drug interactions, and side effects are limited. In a review of the available evidence, CBD does not appear to change appetite or alter physiologic parameters, psychomotor functioning, or gastrointestinal transit time.27 Studies suggest chronic dosing of CBD up to 1500 mg/d is well tolerated.24 CBD does appear to affect hepatic drug metabolism and p-glycoprotein transporters.24 Pure CBD does not appear to have any recreational or abuse potential. In a World Health Organization report, the available literature reviewed demonstrated CBD to be well tolerated with a favorable safety profile.32

The FDA encourages clinicians to warn patients about purchasing CBD products online. “Selling unapproved products with unsubstantiated therapeutic claims — such as claims that CBD products can treat serious diseases and conditions — can put patients and consumers at risk by leading them to put off important medical care. Additionally, there are many unanswered questions about the science, safety, effectiveness and quality of unapproved products containing CBD,” said Acting FDA Commissioner Ned Sharpless, MD.33

CBD Drug Development Pipeline

Despite the availability of CBD in retail settings, CBD drug development is still an essential step toward the adoption and understanding of cannabis-based medicine. The rigorous drug development process provides valuable insight into the pharmacologic effects of a drug through phase 1, 2, and 3 studies. Drug development also provides a means of accountability for manufacturers through regulatory and peer-reviewed methods of oversight. To that end, several pure CBD drugs are currently in development (Table 3).34-38