A. Landschaft (1,2), D. Stepensky (3)

1. Boston Children’s Hospital, Boston, MA 02115

2. Copeia GmbH, Bergisch Gladbach, Germany D51469

3. Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel 8410501

Introduction: THC-containing cannabis products are used for medicinal purposes by wide populations of patients. THC has been reported to have variable pharmacokinetics following consumption by different routes, which limits its clinical safety and effectiveness, and requires extensive titration and monitoring of patients that use cannabis products. There are substantial differences in the exposure to the THC and in the values of its pharmacokinetic parameters that were reported in different clinical trials.

Aims: To retrieve and assess the available clinical data on the pharmacokinetics of THC in human subjects or patients following consumption of different cannabis products.

Methods: Publications on clinical pharmacokinetics of THC were retrieved from the PubMed database, Cmax and AUC of THC and its metabolites, and subjects’ demographic data were retrieved according to the PRISMA guidelines. These data were summarized and analyzed to reveal the extent of the available data and its variability.

Results: We identified 39 publications that matched the search criteria and included quantitative data on Cmax and AUC of THC and its metabolites. Majority of the retrieved datasets were small (mean: 18.84, 95% CI [12.43, 25.25])),originated from young volunteers (25 datasets, mean: 29.55, 95% CI [26.73, 32.37]), mostly male, cannabis-naïve or with previous experience with cannabis. The investigated products were cigarette, inhaler vaporizer, and oral/oromucosal (31, 17, and 10 datasets, respectively). Cmax and AUC of THC and of its metabolites were highly variable, within the individual datasets, and between the datasets.

Conclusions: THC is characterized by high intersubject pharmacokinetic variability, following consumption of different cannabis products. The extent of intra-subject variability cannot be assessed based on the available data, and requires further investigation. THC pharmacokinetic data in patients are scarce, and no conclusions regarding the THC pharmacokinetic variability in relation to patients’ age, gender, genotype/phenotype, disease state, etc. can be made based on the available data. More rich pharmacokinetic THC data from clinical trials in patients with different diseases, and “real world” data are needed to reveal the extent of the inter- and intra-subject pharmacokinetic variability of THC and to identify the variability factors.

Keywords: THC, cannabis, pharmacokinetics, variability factors, systematic review.

This abstract is listed in the journal: «Medical Cannabis and Cannabinoids» (Karger Publishers, Basel, Switzerland) is the official journal of SSCM Swiss Society of Cannabis in Medicin and the SSCM-IACM IACM - International Association for Cannabinoid Medicines Cannabinoid Conference 2022. Cannabis Medicinalis