Hydromorphone

For an informed discussion with your doctor or pharmacist. This information collection is not a clinically validated interaction checker. Missing data do not establish safety. Do not change or stop prescribed medicines on the basis of this information. The findings apply to the specific conditions studied; laboratory and animal studies cannot be directly extrapolated to humans.

Active substance: Hydromorphone

Examples of brand names: Palladon [DE]

ATC code: N02AA03

Main use (for orientation): Severe pain

Documented research summary

Several controlled human studies: dronabinol plus oral hydromorphone showed no consistent synergistic analgesia in healthy adults, n=29, or knee osteoarthritis, n=37 or n=21, with sometimes more adverse/subjective effects. CBD 50/100/200 mg plus hydromorphone 4 mg in n=31 improved some acute but not chronic laboratory-pain parameters; more negative/adverse effects at 200 mg. The 2025 human-liver-microsome/UGT2B7 paper including THC/11-OH-THC/CBD/7-OH-CBD and a modelled CBD-related hydromorphone AUC increase of 22% in healthy people or 25% in moderate hepatic impairment is not a measured human pharmacokinetic effect. A 2026 respiratory-depression case after a 100 mg THC/CBD product with hydromorphone patient-controlled analgesia and methadone, reversible with naloxone, cannot be attributed to an individual pair.

Uncertainties and limitations

Different doses, healthy people versus chronic pain, short observation. Do not generalise to chronic high-dose opioids; UGT model not clinically confirmed.

Separately recorded findings

2 separately recorded findings. Each statement applies to its documented study context.

CBD – laboratory and animal studies

Finding ID: B0110

Type of result: Context-specific finding; read the limitations

Observation: CBD competitively inhibits hydromorphone glucuronidation in human liver microsomes: unbound Ki 0.068±0.003 µM. The PBPK model predicts oral immediate-release hydromorphone AUC ratios of 1.22 in healthy people and 1.25 in moderate hepatic impairment (Child–Pugh B), i.e. +22% and +25%. Not a measured human pair interaction.

Mechanism: Competitive UGT2B7 inhibition

Study type: In vitro and PBPK model

Context studied: Virtual interaction study: oral CBD 1500 mg every 12 hours for seven days, single oral immediate-release hydromorphone 8 mg during CBD administration. Model cohorts: healthy adults and moderate hepatic impairment (Child–Pugh B). Doses exclusively simulation parameters; exact hydromorphone day contradictory in the original (methods 2.13: day 7; Table 6 footnote b: day 6).

Clinical interpretation: Possible relevance with a narrow therapeutic range; unconfirmed

Limitations and uncertainties: In-vitro/model result, not an observed CBD–hydromorphone interaction in patients. Static models predict substantially larger effects. The PBPK interaction was not clinically validated because clinical pair data were absent; 7-OH-CBD and pharmacodynamic combination effects were not included in the inhibitor model. Internal contradiction concerning simulation day (6 versus 7); do not infer a dosing regimen from these values.

Original sources for this finding: UGT2B7-mediated drug-drug interaction between cannabinoids and hydromorphone [ME12]

THC – laboratory and animal studies

Finding ID: B0111

Type of result: Context-specific finding; read the limitations

Observation: THC competitively inhibits UGT2B7-mediated hydromorphone glucuronidation in human liver microsomes: unbound Ki 0.17±0.02 µM, corrected for non-specific binding.

Mechanism: Competitive UGT2B7 inhibition

Study type: In vitro and static modelling

Context studied: Hydromorphone-specific liver-microsome assay; unbound Ki corrected using previously published unbound incubation fractions. THC metabolites investigated separately; a different inhibition model was used for 11-OH-THC, for example.

Clinical interpretation: Clinical effect unresolved

Limitations and uncertainties: Not a measured clinical THC–hydromorphone pair interaction. Unbound Ki is a laboratory parameter, not a human hazard threshold. CBD PBPK predictions of +22%/+25% must not be extrapolated to THC; THC was statically modelled in this publication.

Original sources for this finding: UGT2B7-mediated drug-drug interaction between cannabinoids and hydromorphone [ME12]

References and access status

[CA_L_D0141] DILAUDID (HYDROMORPHONE HYDROCHLORIDE) INJECTION, SOLUTION [FRESENIUS KABI USA, LLC]

Original source / bibliographic reference

Authors: Fresenius Kabi USA, LLC

Year: 2026

Source type: Current published human-use SPL / product information

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

[ME12] UGT2B7-mediated drug-drug interaction between cannabinoids and hydromorphone

Original source / bibliographic reference

Authors: Coates S; Bardhi K; Zhao M; Lazarus P

Year: 2025

Source type: Original study: in vitro UGT and PBPK

DOI: 10.1016/j.dmd.2025.100135

PMID: 40925219

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

PubMed – bibliographic reference / abstract

DOI – publisher access (access restrictions may apply)

Europe PMC – full-text access according to the literature database – Listed as freely available HTML full text in the official Europe PMC metadata. Direct retrieval was not fully verified here.

[CA_P_41481837] Evaluating the Acute Effects of the Cannabinoid Dronabinol and the Opioid Hydromorphone Alone and in Combination: A Double-blind, Randomized, Placebo-controlled Trial in Knee Osteoarthritis.

Original source / bibliographic reference

Authors: Hamilton KR, Mun CJ, Sadik E, Bergeria CL, Huhn AS, Speed TJ, Vandrey R, Dunn KE, Campbell CM.

Year: 2026

Source type: research-article; Randomized Controlled Trial; Journal Article

DOI: 10.1097/aln.0000000000005925

PMID: 41481837

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

PubMed Central – full-text access according to the literature database – Archive attribution confirmed by Europe PMC metadata. Direct retrieval was not fully verified here; access may require a browser check.

Europe PMC – full-text access according to the literature database – Listed as freely available HTML full text in the official Europe PMC metadata. Direct retrieval was not fully verified here.

[CA_P_42822008] Respiratory depression with concomitant use of opioids and cannabinoids: a case report.

Original source / bibliographic reference

Authors: Messick CL, Svendsen M, Codding J, Rejbi M.

Year: 2026

Source type: Journal Article

DOI: 10.1080/00325481.2026.2739680

PMID: 42822008

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[CA_P_40839659] A within-subject, double-blind, placebo-controlled randomized evaluation of the combined effects of cannabidiol and hydromorphone in a human laboratory pain model.

Original source / bibliographic reference

Authors: Bergeria CL, Mun CJ, Speed TJ, Huhn AS, Wolinsky D, Vandrey R, Campbell CM, Dunn KE.

Year: 2025

Source type: research-article; Randomized Controlled Trial; Journal Article

DOI: 10.1097/j.pain.0000000000003561

PMID: 40839659

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

PubMed Central – full-text access according to the literature database – Archive attribution confirmed by Europe PMC metadata. Direct retrieval was not fully verified here; access may require a browser check.

Europe PMC – full-text access according to the literature database – Listed as freely available HTML full text in the official Europe PMC metadata. Direct retrieval was not fully verified here.

[CA_P_37202479] Within-subject, double-blind, randomized, placebo-controlled evaluation of combining the cannabinoid dronabinol and the opioid hydromorphone in adults with chronic pain.

Original source / bibliographic reference

Authors: Campbell CM, Mun CJ, Hamilton KR, Bergeria CL, Huhn AS, Speed TJ, Vandrey R, Dunn KE.

Year: 2023

Source type: research-article; Randomized Controlled Trial; Journal Article; Research Support, N.I.H., Extramural

DOI: 10.1038/s41386-023-01597-1

PMID: 37202479

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

PubMed Central – full-text access according to the literature database – Archive attribution confirmed by Europe PMC metadata. Direct retrieval was not fully verified here; access may require a browser check.

Europe PMC – full-text access according to the literature database – Listed as freely available HTML full text in the official Europe PMC metadata. Direct retrieval was not fully verified here.

[CA_P_33879842] Within-subject, double-blinded, randomized, and placebo-controlled evaluation of the combined effects of the cannabinoid dronabinol and the opioid hydromorphone in a human laboratory pain model.

Original source / bibliographic reference

Authors: Dunn KE, Bergeria CL, Huhn AS, Speed TJ, Mun CJ, Vandrey R, Campbell CM.

Year: 2021

Source type: Clinical Trial, Phase II; research-article; Randomized Controlled Trial; Journal Article; Research Support, N.I.H., Extramural

DOI: 10.1038/s41386-021-01007-4

PMID: 33879842

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

PubMed Central – full-text access according to the literature database – Archive attribution confirmed by Europe PMC metadata. Direct retrieval was not fully verified here; access may require a browser check.

Europe PMC – full-text access according to the literature database – Listed as freely available HTML full text in the official Europe PMC metadata. Direct retrieval was not fully verified here.

[CA_P_31496363] Reduced urinary opioid levels from pain management patients associated with marijuana use.

Original source / bibliographic reference

Authors: Goggin MM, Shahriar BJ, Stead A, Janis GC.

Year: 2019

Source type: Journal Article

DOI: 10.2217/pmt-2019-0017

PMID: 31496363

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

Research as of 23 October 2026. Not all original full texts could be reviewed in full. Source accessibility and the strength of scientific evidence must be assessed separately. An accessible link does not establish medical approval; a bibliographic record with an abstract does not replace the original full text.

Drug search and explanation of the evidence · Guide: cannabinoids and medicines · Author and responsibility