Letter to the Editor: Possible Drug–Drug Interactions Between Cannabinoids and Candidate COVID-19 Drugs

Introduction

Cannabinoid preparations are available across the globe as regulatory agency-approved medicines, through medical cannabis programs, and as hemp-derived products. Many regions, including most provinces in Canada, have designated cannabis businesses as ‘‘essential’’ services during the coronavirus disease 2019 (COVID-19) pandemic, and sales of cannabis remain strong in an otherwise economically challenging time. In light of the potential increased use of cannabis and a recent surge in research to rapidly identify medications to treat COVID-19, it is critical to delineate possible pharmacokinetic (PK) and pharmacodynamic (PD) drug–drug interactions (DDIs) between cannabinoids and such experimental medications. Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are lipophilic, highly protein bound, have a large volume of distribution, a long half-life, bioaccumulate, and share common metabolic pathways within the cytochrome P450 (CYP450) family (e.g., 3A4, 2C9, and 2C19), drug trans- porters (e.g., breast cancer resistance protein), and plasma protein-binding substrates. Both THC and CBD have been shown to have clinically significant PK (e.g., warfarin and clobazam) and PD interactions (e.g., valproic acid). The severity of some cannabinoid DDIs, such as potential hepatocellular injury and sedation further highlights the importance of early identification of possible interactions between cannabinoids and medications that may be used to treat COVID-19.