Summary
Nicotine 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 8 registered trials linking Nicotine to Opioid Use Disorder: 2 are currently recruiting; 1 is active or not yet recruiting; 4 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 2 (NCT04092101). The largest enrolment is 10000 participants (NCT06552741). Registration activity spans 2011 to 2024. The literature layer holds 13 publications for this pair: 3 Cochrane reviews, 3 meta-analyses, 1 systematic review, 1 randomised controlled trial publication and 5 clinical trial publications. Publication years run from 2003 to 2026. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
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 | 70.5 (trials 20.5, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 2 recruiting, 1 active / not yet recruiting, 4 completed, 1 other |
| Linked publications | 13 (5 clinical trial publications, 3 Cochrane reviews, 3 meta-analyses, 1 systematic review, 1 randomised controlled trial publication) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | Open Targets, ChEMBL |
| Linked via biomarker / target | ADCY1 |
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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT04092101 | Low Nicotine Content Cigarettes in Vulnerable Populations: Opioid Use Disorder 2020 | completed | Phase 2 | 326 |
| NCT05290025 | Easy Access to Smoking Cessation for People Receiving Opioid Agonist Therapy Who Are Smoking Tobacco 2022 | active, not recruiting | Not applicable | 266 |
| NCT02250664 | Project 2, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in Opioid Abusers 2016 | completed | PHASE1, PHASE2 | 775 |
| NCT06277271 | E-cigarettes as a Harm Reduction Strategy 2023 | completed | Not applicable | 30 |
| NCT01386138 | Treating South African Pregnant Women for Methamphetamine 2011 | completed | Not applicable | 60 |
| NCT03745339 | Outcome Inference in the Sensory Preconditioning Task in Opioid-Use Disorder 2019 | recruiting | Not applicable | 150 |
| NCT06552741 | Screening, Evaluation and Assessment (SEA) Protocol at the NIDA IRP 2024 | recruiting | Not applicable | 10,000 |
| NCT01395797 | Pioglitazone for Heroin and for Nicotine Dependence 2011 | terminated | PHASE1, PHASE2 | 82 |
Published literature
- Clinical trial publication Assessing the impact of nicotinic partial agonists compared to NRT on opioid and cigarette use: A secondary analysis investigating treatment outcomes for co-occurring nicotine and opioid useRich ZC, Tindle HA, Cheng DM et al. · Journal of substance use and addiction treatment · 2026 · PMID 41558587
- Clinical trial publication Integrated Nicotine Replacement and Behavioral Support to Reduce Smoking in Opioid Agonist Therapy: A Randomized Clinical TrialDruckrey-Fiskaaen KT, Madebo T, Daltveit JT et al. · JAMA psychiatry · 2025 · PMID 39937506
- Clinical trial publication Exposure to Bupropion-SR vs. Placebo is associated with reductions in smoking among persons receiving methadone with no stated interest in smoking cessationWare OD, Stitzer ML, Umbricht A et al. · Addictive behaviors · 2025 · PMID 39509950
- Meta-analysis Analgesic potential of transdermal nicotine patch in surgery: a systematic review and meta-analysis of randomised placebo-controlled trialsda Silva Barbirato D, de Melo Vasconcelos AF, Dantas de Moraes SL et al. · European journal of clinical pharmacology · 2023 · PMID 36947193
- Clinical trial publication FORWARDS-1: an adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment-a pharmacokinetic-pharmacodynamic studyPaterson LM, Barker D, Cro S et al. · Trials · 2022 · PMID 36258248
- Clinical trial publication Transcranial direct current stimulation of the frontal-parietal-temporal brain areas reduces cigarette consumption in abstinent heroin usersMeng Z, Li Q, Ma Y et al. · Journal of psychiatric research · 2022 · PMID 35785574
- Randomized controlled trial Effect of brief nicotine corrective messaging on nicotine beliefs in persons who use opioidsParker MA, Byers JE, Villanti AC · Experimental and clinical psychopharmacology · 2022 · PMID 34291993
- Cochrane review Association between vaping and health outcomes in patients with opioid use disorder: a systematic review protocolSanger N, D'Elia A, Sanger S et al. · BMJ open · 2021 · PMID 33468604
- Meta-analysis Effects of stimulant drug use on the dopaminergic system: A systematic review and meta-analysis of in vivo neuroimaging studiesProebstl L, Kamp F, Manz K et al. · European psychiatry : the journal of the Association of European Psychiatrists · 2019 · PMID 30981746
- Cochrane review Screening, treatment initiation, and referral for substance use disordersBernstein SL, D'Onofrio G · Addiction science & clinical practice · 2017 · PMID 28780906
- Meta-analysis BDNF rs6265 polymorphism and drug addiction: a systematic review and meta-analysisHaerian BS · Pharmacogenomics · 2013 · PMID 24279859
- Systematic review Pharmacotherapy for pregnant women with addictionsRayburn WF, Bogenschutz MP · American journal of obstetrics and gynecology · 2004 · PMID 15592269
- Cochrane review [Naltrexone in the treatment of addiction]Bachs L, Waal H · Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke · 2003 · PMID 12821984
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL, in this case via the biomarker or target ADCY1. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Nicotine approved for Opioid Use Disorder?
Nicotine 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 Nicotine in clinical trials for Opioid Use Disorder?
ClinicalTrials.gov lists 8 registered trials linking Nicotine to Opioid Use Disorder: 2 are currently recruiting; 1 is active or not yet recruiting; 4 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 2 (NCT04092101). The largest enrolment is 10000 participants (NCT06552741). Registration activity spans 2011 to 2024.
What does the evidence show for Nicotine in Opioid Use Disorder?
Nicotine has both completed registered trials and synthesis-level publications linked to Opioid Use Disorder. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL, in this case via the biomarker or target ADCY1. 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.