THC and CBD can inhibit hydromorphone metabolism, potentially increasing opioid levels by 20-30%
In vitro and modeling studies found THC, CBD, and their metabolites inhibit the enzyme that breaks down hydromorphone, with CBD predicted to increase hydromorphone exposure by 20-30% in humans.
Quick Facts
What This Study Found
Multiple cannabinoids inhibited UGT2B7-mediated hydromorphone glucuronidation with Ki values 0.068-1.01 uM; static modeling predicted >1.25-fold increase in hydromorphone exposure; PBPK models predicted 20-30% CBD-hydromorphone interaction in healthy and cirrhotic individuals.
Key Numbers
Ki values 0.068-1.01 uM after binding correction; THC, 11-OH-THC, CBD, and 7-OH-CBD all predicted to cause >1.25-fold hydromorphone increase; CBD predicted 20-30% increase via PBPK modeling.
How They Did This
In vitro inhibition screening in human liver microsomes and recombinant UGT2B7; IC50 and Ki determinations; static and PBPK modeling for in vivo prediction; tested THC, CBD, and their major metabolites.
Why This Research Matters
Patients using cannabis alongside hydromorphone (a potent opioid for severe pain) may experience higher opioid levels than expected, increasing overdose risk.
The Bigger Picture
As cannabis-opioid co-use becomes more common in pain management, understanding pharmacokinetic interactions is critical for patient safety.
What This Study Doesn't Tell Us
In vitro data with in silico predictions; clinical interaction studies needed for confirmation; UGT2B7 polymorphism effects uncertain; did not account for all potential metabolic pathways.
Questions This Raises
- ?Should hydromorphone doses be adjusted for cannabis users?
- ?Do these interactions apply to other opioids metabolized by UGT2B7?
- ?Is the 20-30% increase clinically significant for overdose risk?
Trust & Context
- Key Stat:
- CBD predicted to increase hydromorphone exposure by 20-30% through enzyme inhibition
- Evidence Grade:
- Rigorous in vitro pharmacology with PBPK modeling prediction, but clinical confirmation needed before changing dosing practice.
- Study Age:
- Published 2025
- Original Title:
- UGT2B7-mediated drug-drug interaction between cannabinoids and hydromorphone.
- Published In:
- Drug metabolism and disposition: the biological fate of chemicals, 53(9), 100135 (2025)
- Authors:
- Coates, Shelby(2), Bardhi, Keti(2), Zhao, Mengqi(2), Lazarus, Philip
- Database ID:
- RTHC-06239
Evidence Hierarchy
Watches what happens naturally without intervening.
What do these levels mean? →Frequently Asked Questions
Can cannabis affect opioid levels?
Yes. This study found THC and CBD inhibit the enzyme (UGT2B7) that breaks down hydromorphone, with modeling predicting a 20-30% increase in opioid exposure when both are used together.
Is this dangerous?
A 20-30% increase in hydromorphone levels could be clinically significant, especially in patients with liver disease. Clinical studies are needed to confirm the prediction and determine if dose adjustments are warranted.
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Cite This Study
https://rethinkthc.com/research/RTHC-06239APA
Coates, Shelby; Bardhi, Keti; Zhao, Mengqi; Lazarus, Philip. (2025). UGT2B7-mediated drug-drug interaction between cannabinoids and hydromorphone.. Drug metabolism and disposition: the biological fate of chemicals, 53(9), 100135. https://doi.org/10.1016/j.dmd.2025.100135
MLA
Coates, Shelby, et al. "UGT2B7-mediated drug-drug interaction between cannabinoids and hydromorphone.." Drug metabolism and disposition: the biological fate of chemicals, 2025. https://doi.org/10.1016/j.dmd.2025.100135
RethinkTHC
RethinkTHC Research Database. "UGT2B7-mediated drug-drug interaction between cannabinoids a..." RTHC-06239. Retrieved from https://rethinkthc.com/research/coates-2025-ugt2b7mediated-drugdrug-interaction-between
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.