Comparative Pharmacokinetic Assessment of Innovative Sublingual, Rectal and Vaporizer Cannabis Products Versus Approved Cannabis Products in Healthy Volunteers.

ABSTRACT

Background: Over the last years, there is a dramatic increase in the use of medical cannabis products for an expanding range of clinical indications. The type of the drug product and its administration route affect substantially the rate and the extent of absorption of cannabinoids and the effects induced by them in the patients. The current challenge for the cannabis pharmaceutical industry is to develop formulations that allow predictable and stable absorption of cannabinoids. This article reports the results of the clinical trial that investigated the pharmacokinetics (PKs) of innovative cannabis products in healthy volunteers. Materials and Methods: This was a single-center study with a single-dose, randomized, crossover, partially blinded controlled design. Each of the 12 healthy volunteers received 8 different products, of the 10 products that were assessed in this trial novel sublingual (SL) tablet, vaporizer, and rectal products, comparator products (Sativex® and oil-based oromucosal products), and placebo products. Serial blood samples were collected, plasma concentrations of the THC, 11-OH-THC, and CBD were quantified and subjected to noncompartmental PK analysis. Results: Novel medical cannabis products that were investigated in the study induced substantial exposure of the volunteers to the active ingredients, had more rapid absorption, and in some cases also less variable absorption of THC and CBD, in comparison with the approved comparison products. The bioavailability of the novel SL tablet-based and suppositories products was somewhat lower than that of the oromucosal products. The vaporizer provided immediate systemic absorption with highest maximal concentration. The safety profile of the novel cannabis products, namely vaporizer, SL tablets, and suppositories, was not inferior to the Sativex and oil-based oromucosal formulations. Conclusions: The novel cannabis products that were assessed in this study have PK properties that may be advantageous for management of specific medical conditions or in specific subgroups of patients that are prescribed medical cannabis.