Cannabidiol's impact on drug-metabolization

Area of Science:

• Pharmacology
• Drug Metabolism
• Cannabinoid Research

Background:

• Cannabidiol (CBD) is widely accessible.
• CBD is known to inhibit numerous drug-metabolizing proteins (DMPs), including Cytochrome P450 (CYP) enzymes, carboxylesterase 1 (CES1), uridine 5'diphospho-glucoronosyltransferase (UGT) enzymes, P-glycoprotein (P-gp), and Breast Cancer Resistance Protein (BCRP).
• The clinical significance of these potential CBD-drug interactions remains largely uncharacterized.

Purpose of the Study:

• To identify drugs that are substrates of DMPs potentially interacting with orally ingested CBD.
• To determine if CBD-drug interactions have been documented in scientific literature.
• To assess the prevalence of DMP substrates among frequently prescribed medications.

Main Methods:

• Systematic identification of 403 drugs as substrates of DMPs.
• Literature review to find reported CBD-drug interactions (human, in vivo, in vitro).
• Analysis of DMP substrate frequency among top prescribed drugs in Germany and the USA.

Main Results:

• CBD-drug interactions were reported for 53 out of 403 identified DMP substrates.
• In most reported cases (31/53), CBD increased substrate levels; one case showed a decrease, and four showed no change.
• Controversial results were observed for 5/53 substrates, with no levels reported for 12/53.
• A significant proportion of frequently prescribed drugs (67% in Germany, 68% in the USA) are substrates of DMPs.

Conclusions:

• There is an urgent need for comprehensive pharmacological studies on CBD-drug interactions.
• Patient education regarding potential risks and increased physician awareness are essential.
• Regulatory authorities should address this issue internationally to enhance CBD safety.