Drug-Cannabinoid Interactions in Selected Therapeutics for Symptoms Associated with Epilepsy, Autism Spectrum Disorder, Cancer, Multiple Sclerosis, and Pain
Maria G Campos 1 2, Maria China 1, Mariana Cláudio 1, Miguel Capinha 1, Rita Torres 1, Simão Oliveira 1, Ana Fortuna 1 3 4
1 Observatory of Drug-Herb Interactions, Faculty of Pharmacy, University of Coimbra, Health Science Campus, Azinhaga Santa Comba, 3000-548 Coimbra, Portugal.
2 Coimbra Chemistry Centre (CQC, FCT Unit 313) (FCTUC), University of Coimbra, Rua Larga, 3004-531 Coimbra, Portugal.
3 Laboratory of Pharmacology and Pharmaceutical Care, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
4 CIBIT-Coimbra Institute for Biomedical Imaging and Translational Research, ICNAS, University of Coimbra, 3000-548 Coimbra, Portugal.
Affiliationer
Clinical practice entails a translation of research that assists in the use of scientific data and therapeutic evidence for the benefit of the patient. This review critically summarizes the potential impact of cannabinoids in conjunction with other drugs when associated with treatments for epilepsy, autism spectrum disorder, cancer, multiple sclerosis, and chronic pain. In these associations, potential drug interactions may occur and alter the predicted clinical results. Therefore, the potential for drug interactions must always be assessed to avoid therapeutic failures and/or increased side effects. Some effects may be additive, synergistic, or antagonistic, but changes in absorption, distribution, metabolism, particularly through cytochrome P450 (CYP) isoenzymes (e.g., CYP2C9 and CYP3A4), and excretion may also occur. For example, the combination of cannabis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases the plasma concentration of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In contrast, rifampicin, a CYP3A4 inducer, stands out for reducing plasma THC levels by approximately 20-40% and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Pharmacokinetic interactions with anticonvulsant medications have also been reported, as have pharmacodynamic interactions between cannabinoids and medications with sympathomimetic effects (e.g., tachycardia, hypertension), central nervous system depressants (e.g., drowsiness, ataxia), and anticholinergics (e.g., tachycardia and somnolence). Although further studies are still pending, there is currently clinical evidence supporting drug interactions with cannabinoids, requiring doctors to evaluate the risk of drug combinations with cannabinoids and vice versa. The tables provided here were designed to facilitate the identification of biorelevant interactions that may compromise therapeutic efficacy and toxicity.
Keywords: CBD; autism spectrum disorder; cancer; cannabinoids; cytochrome P450; drug–drug interactions; epilepsy; tetrahydrocannabinol.