Summary
Yohimbine 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 3 registered trials linking Yohimbine to Opioid Use Disorder: 1 is active or not yet recruiting; 1 has completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 2 (NCT04231708). The largest enrolment is 26 participants (NCT03015246). Registration activity spans 2016 to 2026. The literature layer holds 3 publications for this pair: 3 clinical trial publications. Publication years run from 2002 to 2013. 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 | 33.0 (trials 7.0, literature 6.0, tier 15, approved bonus 5.0) |
| Registered trials | 3 total: 0 recruiting, 1 active / not yet recruiting, 1 completed, 1 other |
| Linked publications | 3 (3 clinical trial publications) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | inhibitor |
| 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT04231708 | Effects of Pharmacological Stress and rTMS on Executive Function in Opioid Use Disorder 2026 | not yet recruiting | Phase 2 | 20 |
| NCT04181515 | Using rTMS to Explore Neural Mechanisms of Stress-Induced Opioid Use 2023 | withdrawn | Phase 2 | — |
| NCT03015246 | Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence 2016 | completed | PHASE1, PHASE2 | 26 |
Published literature
- Clinical trial publication Yohimbine increases opioid-seeking behavior in heroin-dependent, buprenorphine-maintained individualsGreenwald MK, Lundahl LH, Steinmiller CL · Psychopharmacology · 2013 · PMID 23161001
- Clinical trial publication Clonidine and yohimbine in opioid-dependent humans responding under a naloxone novel-response discrimination procedureOliveto A, Sevarino K, McCance-Katz E et al. · Behavioural pharmacology · 2003 · PMID 12658070
- Clinical trial publication Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patientsStine SM, Southwick SM, Petrakis IL et al. · Biological psychiatry · 2002 · PMID 11955464
Mechanism and notes
Recorded mechanism or class: inhibitor.
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 Yohimbine approved for Opioid Use Disorder?
Yohimbine 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 Yohimbine in clinical trials for Opioid Use Disorder?
ClinicalTrials.gov lists 3 registered trials linking Yohimbine to Opioid Use Disorder: 1 is active or not yet recruiting; 1 has completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 2 (NCT04231708). The largest enrolment is 26 participants (NCT03015246). Registration activity spans 2016 to 2026.
What does the evidence show for Yohimbine in Opioid Use Disorder?
Yohimbine has 1 completed trial and 3 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.