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.
Pain management physicians, pharmacists, clinical pharmacologists
CBD predicted to increase hydromorphone exposure by 20-30% through enzyme inhibition
What the researchers 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.
Why it matters
Patients using cannabis alongside hydromorphone (a potent opioid for severe pain) may experience higher opioid levels than expected, increasing overdose risk.
The numbers in context
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 the study worked
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.
What this study cannot 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.
How to read the evidence
Rigorous in vitro pharmacology with PBPK modeling prediction, but clinical confirmation needed before changing dosing practice.
When this study was published
Published 2025
The bigger picture
As cannabis-opioid co-use becomes more common in pain management, understanding pharmacokinetic interactions is critical for patient safety.
Questions still open
- 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?
Common questions
Can cannabis affect opioid levels?
Is this dangerous?
Read the original research
UGT2B7-mediated drug-drug interaction between cannabinoids and hydromorphone.
Drug metabolism and disposition: the biological fate of chemicals, 53(9), 100135
Citation
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
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