Summary
Norepinephrine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Opioid Use Disorder would be drug repurposing rather than first-in-human development. This does not mean it is approved for Opioid Use Disorder. ClinicalTrials.gov lists 1 registered trial linking Norepinephrine to Opioid Use Disorder: 1 has completed. The most advanced is Phase 4 (NCT03271151). It plans or enrolled 160 participants. Registered activity dates to 2017. The literature layer holds 5 publications for this pair: 5 clinical trial publications. Publication years run from 2008 to 2022. These are primary trial reports rather than syntheses, so results have not yet been pooled or graded independently.
The RepurpOS disease-intelligence file for Opioid Use Disorder ranks 289 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: Spontaneous recovery (without MOUD) in 20-30% of OUD patients over 10 years; but overdose mortality risk during active disorder is extreme (5-10 per 1000 person-years); relapse rate 90%+ in first year after discontinuing MOUD.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 34.5 (trials 4.5, literature 10.0, tier 15, approved bonus 5.0) |
| Registered trials | 1 total: 0 recruiting, 0 active / not yet recruiting, 1 completed, 0 other |
| Linked publications | 5 (5 clinical trial publications) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | agonist |
| Data sources | DGIdb |
| Linked via biomarker / target | ADRA2C |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT03271151 | Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty 2017 | completed | Phase 4 | 160 |
Published literature
- Clinical trial publication Effect of Duloxetine on Opioid Use and Pain After Total Knee Arthroplasty: A Triple-Blinded Randomized Controlled TrialYaDeau JT, Mayman DJ, Jules-Elysee KM et al. · The Journal of arthroplasty · 2022 · PMID 35346549
- Clinical trial publication Pharmacogenetic randomized trial for cocaine abuse: disulfiram and α1A-adrenoceptor gene variationShorter D, Nielsen DA, Huang W et al. · European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2013 · PMID 23849431
- Clinical trial publication Pharmacogenetic randomized trial for cocaine abuse: disulfiram and dopamine β-hydroxylaseKosten TR, Wu G, Huang W et al. · Biological psychiatry · 2013 · PMID 22906516
- Clinical trial publication Clonidine improved laboratory-measured decision-making performance in abstinent heroin addictsZhang XL, Wang GB, Zhao LY et al. · PloS one · 2012 · PMID 22291886
- Clinical trial publication Venlafaxine for acute heroin detoxification: a double-blind, randomized, control trialLin SK, Chen CH, Pan CH · Journal of clinical psychopharmacology · 2008 · PMID 18344729
Mechanism and notes
Recorded mechanism or class: agonist.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ADRA2C. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Norepinephrine approved for Opioid Use Disorder?
Norepinephrine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Opioid Use Disorder would be drug repurposing rather than first-in-human development. This does not mean it is approved for Opioid Use Disorder. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Norepinephrine in clinical trials for Opioid Use Disorder?
ClinicalTrials.gov lists 1 registered trial linking Norepinephrine to Opioid Use Disorder: 1 has completed. The most advanced is Phase 4 (NCT03271151). It plans or enrolled 160 participants. Registered activity dates to 2017.
What does the evidence show for Norepinephrine in Opioid Use Disorder?
Norepinephrine has 1 completed trial and 5 linked publications for Opioid Use Disorder. Completed trials may or may not have posted results; follow the NCT links to check. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ADRA2C. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.