Delta-8-THC Can Cause Significant Drug Interactions by Inhibiting Liver Enzymes | Research

The takeaway

Delta-8-THC and its active metabolite significantly inhibit CYP2C9 and CYP3A4 liver enzymes, potentially causing clinically relevant drug interactions — especially with oral consumption.

Delta-8-THC consumers, pharmacists, healthcare providers managing patients on CYP-metabolized drugs, and regulators evaluating delta-8-THC safety.

What the researchers found

Delta-8-THC competitively inhibited CYP2C9-mediated warfarin metabolism and non-competitively inhibited CYP2C9 and CYP3A4 metabolism of other substrates. Static modeling predicted clinically relevant interactions, particularly with oral delta-8-THC. The inactive metabolite (11-nor-delta-8-THC-9-carboxylic acid) showed no inhibition.

Why it matters

Delta-8-THC is widely available in states where delta-9-THC is restricted, but its drug interaction potential was unknown. This study reveals significant risks for people taking common medications metabolized by CYP2C9 (like warfarin) and CYP3A4.

The numbers in context

Significant inhibition of CYP2C9 and CYP3A4. Competitive inhibition of CYP2C9-warfarin. Non-competitive inhibition of CYP2C9-diclofenac and CYP3A4-midazolam. 11-nor-delta-8-THC-9-carboxylic acid: no inhibition.

How the study worked

In vitro enzyme inhibition study using recombinant P450-overexpressing microsomes and pooled human liver microsomes, with Lineweaver-Burk kinetic analysis and static drug interaction modeling.

What this study cannot tell us

In vitro study — actual clinical drug interactions depend on achievable tissue concentrations. Static modeling may over- or underpredict real-world interactions. Individual variation in enzyme activity not captured.

How to read the evidence

Rigorous in vitro pharmacology with appropriate kinetic analysis and modeling — strong mechanistic evidence though clinical validation needed.

When this study was published

First-ever characterization of delta-8-THC drug interaction potential, addressing a critical safety gap in the rapidly growing delta-8 market.

The bigger picture

The delta-8-THC market has exploded in regulatory grey areas. This is the first study to characterize its drug interaction potential, revealing risks that consumers and healthcare providers need to know about.

Questions still open

Should delta-8-THC products carry drug interaction warnings? Are people on blood thinners (warfarin) at particular risk from delta-8-THC use?

Common questions

Can delta-8-THC interact with medications?

Yes — this study shows it significantly inhibits two major liver enzymes (CYP2C9 and CYP3A4) that metabolize many common drugs, including warfarin, diclofenac, and midazolam.

Is oral delta-8-THC riskier for drug interactions than smoking?

Yes — the modeling predicted higher interaction risk with oral consumption because it results in higher liver concentrations of delta-8-THC than inhaled forms.

Read the original research

Inhibitory effects of Δ8-tetrahydrocannabinol on major hepatic cytochrome P450 enzymes and implications for drug disposition.

Drug metabolism and disposition: the biological fate of chemicals, 53(9), 100122

View on PubMed ↗Publisher’s paper ↗

Citation

Zhao, Mengqi; Coates, Shelby; Bardhi, Keti; Lazarus, Philip. (2025). Inhibitory effects of Δ8-tetrahydrocannabinol on major hepatic cytochrome P450 enzymes and implications for drug disposition.. Drug metabolism and disposition: the biological fate of chemicals, 53(9), 100122. https://doi.org/10.1016/j.dmd.2025.100122