What topics does this cannabis study cover?

This study covers research on: CBD, Epilepsy.

Lab study links CYP3A4 inhibition to altered CBD metabolism

Q: What did this research study find?

*CYP3A4* inhibition **markedly reduced the laboratory clearance of both *CBD* and 7-OH-CBD**.

Q: Where was this research published?

Published in European journal of drug metabolism and pharmacokinetics on September 11, 2026.

Potential Role of CYP3A4 in Determining In Vivo Exposure to Cannabidiol (CBD) and its Active Metabolite 7-OH-CBD: Evidence from an In Vitro Study.

European journal of drug metabolism and pharmacokinetics • September 11, 2026 • Highly Relevant

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AI Summary

This in vitro study examined whether commonly used antiseizure medications could change how CBD and its active metabolite 7-OH-CBD are broken down. Researchers incubated CBD with human liver microsomes—laboratory preparations that model some liver metabolism—and measured CBD, 7-OH-CBD, and 7-COOH-CBD over time. The study did not involve human participants or clinical treatment.

The strongest effects were seen with CYP3A4 inhibition: ketoconazole markedly reduced the laboratory-measured intrinsic clearance of both CBD and 7-OH-CBD. Combinations of four antiseizure medications that act as CYP3A4 substrates reduced 7-OH-CBD clearance more than CBD clearance, while stiripentol substantially reduced CBD clearance and the formation of both measured metabolites. By contrast, CYP2C19 and CYP2C9 inhibitors caused only minor reductions in CBD clearance, and the authors predict that CYP3A4-substrate medications or CYP2C19 inhibitors would produce only modest increases in CBD exposure. Because this was an in vitro experiment, it cannot establish the size, clinical importance, or safety of these interactions in people; this is an abstract-based summary and does not claim review of the full text.

💡 Key Findings

CYP3A4 inhibition markedly reduced the laboratory clearance of both CBD and 7-OH-CBD.

Limited

35%

Stiripentol substantially decreased CBD clearance and reduced formation of both measured metabolites, 7-OH-CBD and 7-COOH-CBD.

Limited

35%

The study predicted that combining CBD with CYP3A4-substrate antiseizure medications or CYP2C19 inhibitors would cause only modest increases in CBD exposure.

Limited

35%

CYP2C19 and CYP2C9 inhibitors produced only minor reductions in CBD intrinsic clearance in the laboratory model.

Limited

35%

📄 Original Abstract

BACKGROUND: Plasma concentration of cannabidiol (CBD) is a determining factor for its antiseizure efficacy. Since CBD bioavailability decreases with increasing dose, pharmacokinetic drug-drug interactions that reduce its metabolic clearance may represent an alternative strategy to increase systemic exposure without further dose escalation. OBJECTIVE: To investigate in vitro how combinations of antiseizure medications (ASMs) with varying cytochrome P450 (CYP450) inhibitory properties influence the metabolism of CBD and 7-OH-CBD. METHODS: CBD was incubated with human liver microsomes (HLMs) either alone or in the presence of combinations of two to four commonly prescribed ASMs. These ASMs included valproic acid, clobazam, stiripentol, topiramate, zonisamide, felbamate, perampanel, ethosuximide, rufinamide, lamotrigine, levetiracetam and gabapentin. CBD, 7-OH-CBD and 7-COOH-CBD concentrations were quantified at eight time points by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Depletion kinetics, metabolite formation rates, and in vitro intrinsic clearance (CLint) were determined. Ketoconazole, ticlopidine and sulfaphenazole were included as positive controls for CYP3A4, CYP2C19 and CYP2C9 inhibition, respectively. RESULTS: Ketoconazole markedly reduced the CLint of both CBD and its active metabolite, 7-OH-CBD. In contrast, CYP2C19 and CYP2C9 inhibitors produced only minor reductions in CBD CLint. Co-incubation with four CYP3A4-substrate ASMs resulted in a greater reduction in 7-OH-CBD CLint than in CBD CLint. Stiripentol also substantially decreased CBD CLint and markedly reduced the formation of both 7-OH-CBD and 7-COOH-CBD. CONCLUSION: ASMs with CYP3A4-inhibitory potential may alter systemic exposure to both CBD and its active metabolite, 7-OH-CBD, as demonstrated in vitro. However, co-administration of CBD with CYP3A4-substrate ASMs or CYP2C19 inhibitors is predicted to result in only modest increases in CBD exposure.

Paper Type

📄 Research

Publication

Journal: European journal of drug metabolism and pharmacokinetics
Published: September 11, 2026
PMID: 42728549
DOI: 10.1007/s13318-026-01032-y

Authors (3)

Nattapon Jaisupa Unit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Box 431, 405 30, Gothenburg, Sweden. nattapon.jaisuapa@gu.se.
Sofia Birgersson Unit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Box 431, 405 30, Gothenburg, Sweden.
Michael Ashton Unit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Box 431, 405 30, Gothenburg, Sweden.