Summary
Nicotine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Schizophrenia would be drug repurposing rather than first-in-human development. This does not mean it is approved for Schizophrenia. ClinicalTrials.gov lists 8 registered trials linking Nicotine to Schizophrenia: 1 is currently recruiting; 6 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 1 (NCT00527020). The largest enrolment is 1000 participants (NCT03332966). Registration activity spans 2003 to 2023. The literature layer holds 16 publications for this pair: 5 Cochrane reviews, 3 meta-analyses, 2 systematic reviews, 1 randomised controlled trial publication and 5 clinical trial publications. Publication years run from 2019 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 Schizophrenia ranks 499 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 full remission rare (<10%); after first episode, ~80% relapse within 5 years without maintenance antipsychotic; functional disability accumulates over time; 20% achieve good long-term outcome.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 70.0 (trials 20.0, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 1 recruiting, 0 active / not yet recruiting, 6 completed, 1 other |
| Linked publications | 16 (5 Cochrane reviews, 5 clinical trial publications, 3 meta-analyses, 2 systematic reviews, 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 | ADRA1A |
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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT00527020 | First Time in Human Study With GSK1018921 2007 | completed | Phase 1 | 27 |
| NCT05301660 | Effect of Nicotine Transdermal Patch on Cognitive Function and Glycolipid Metabolism in Non-smoking Schizophrenia 2022 | status unknown | Early Phase 1 | 80 |
| NCT01010620 | Screening Protocol for Research Participants 2009 | completed | Not applicable | 523 |
| NCT02918630 | E-cigarettes to Promote Smoking Reduction Among Individuals With Schizophrenia 2016 | completed | Not applicable | 7 |
| NCT07190352 | Behavioral Impact and Neural Correlates of Network-based Brain Stimulation in Schizophrenia 2021 | completed | Not applicable | 15 |
| NCT06389266 | Network-Targeted Neuromodulation for Nicotine Dependence in Schizophrenia 2023 | completed | Not applicable | 90 |
| NCT00135772 | Nicotine and Cotinine Levels in Smokers With Schizophrenia and Schizoaffective Disorder - 2 2003 | completed | Not applicable | 100 |
| NCT03332966 | Youth Experiences and Health Study 2019 | recruiting | Not applicable | 1,000 |
Published literature
- Cochrane review Interventions for smoking cessation in inpatient psychiatry settingsPlever S, Kisely SR, Bonevski B et al. · The Cochrane database of systematic reviews · 2026 · PMID 42389948
- Cochrane review Smoking cessation for people with severe mental illness: systematic review and network meta-analysisBekkering GE, Detraux J, López-López JA et al. · BMJ medicine · 2026 · PMID 41709911
- Cochrane review Psychological and Psychosocial Interventions for People With Schizophrenia and Co-Occurring Substance Use Disorders: A Systematic Review and Meta-AnalysisSalahuddin NH, Herlitzius E, Schütz A et al. · JAMA psychiatry · 2026 · PMID 41637064
- Systematic review Values and preferences of patients with severe mental illness regarding smoking cessation interventions: a systematic review with best-fit framework synthesisCoteur K, Tops L, Bekkering GE et al. · BMJ open · 2026 · PMID 42259564
- Clinical trial publication Carcinogen reduction in a randomized controlled study comparing e-cigarette provision to assessment only among people with serious mental illness who smokePratt SI, Ferron JC, Santos M et al. · Drug and alcohol dependence · 2025 · PMID 40505215
- Meta-analysis Effectiveness and safety of repeated transcranial magnetic stimulation for smoking cessation: A systematic review and meta-analysisShang X, Guo L, Wang Y et al. · General hospital psychiatry · 2025 · PMID 40472574
- Systematic review Psychiatric comorbidity in substance use disorders, a systematic review of neuro-imaging findingsTesselaar DRM, Schellekens AFA, Homberg JR et al. · Neuroscience and biobehavioral reviews · 2025 · PMID 40812726
- Clinical trial publication Combining neuroimaging and brain stimulation to test alternative causal pathways for nicotine addiction in schizophreniaDu X, Choa FS, Chiappelli J et al. · Brain stimulation · 2024 · PMID 38453003
- Clinical trial publication Psychomotor Slowing in Psychosis and Inhibitory Repetitive Transcranial Magnetic Stimulation: A Randomized Clinical TrialWalther S, Alexaki D, Weiss F et al. · JAMA psychiatry · 2024 · PMID 38416468
- Clinical trial publication Video consultation and treatment in the community smoking cessation therapy success rates in patients with mental illness: a randomized controlled trialKaasgaard DM, Sørensen MK, Christiansen RB et al. · Nordic journal of psychiatry · 2024 · PMID 38385357
- Clinical trial publication A reduction in cigarette smoking improves health-related quality of life and does not worsen psychiatric symptoms in individuals with serious mental illnessBrady DJ, Phalen PL, Roche DJO et al. · Addictive behaviors · 2024 · PMID 38176326
- Meta-analysis Effects of acute smoking abstinence among people with schizophrenia: A systematic review and meta-analysis of laboratory studiesJohnstone S, Hubbard AN, Schenkel A et al. · Schizophrenia research · 2024 · PMID 39353226
- Meta-analysis Testing the causal relationships of physical activity and sedentary behaviour with mental health and substance use disorders: a Mendelian randomisation studyIob E, Pingault JB, Munafò MR et al. · Molecular psychiatry · 2023 · PMID 37479783
- Randomized controlled trial Effect of a Tobacco Cessation Intervention Incorporating Weight Management for Adults With Serious Mental Illness: A Randomized Clinical TrialDaumit GL, Evins AE, Cather C et al. · JAMA psychiatry · 2023 · PMID 37378972
- Cochrane review Pharmacological interventions for smoking cessation among people with schizophrenia spectrum disorders: a systematic review, meta-analysis, and network meta-analysisSiskind DJ, Wu BT, Wong TT et al. · The lancet. Psychiatry · 2020 · PMID 32828166
- Cochrane review Pharmacological and behavioural interventions to promote smoking cessation in adults with schizophrenia and bipolar disorders: a systematic review and meta-analysis of randomised trialsPearsall R, Smith DJ, Geddes JR · BMJ open · 2019 · PMID 31784428
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 ADRA1A. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Nicotine approved for Schizophrenia?
Nicotine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Schizophrenia would be drug repurposing rather than first-in-human development. This does not mean it is approved for Schizophrenia. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Nicotine in clinical trials for Schizophrenia?
ClinicalTrials.gov lists 8 registered trials linking Nicotine to Schizophrenia: 1 is currently recruiting; 6 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 1 (NCT00527020). The largest enrolment is 1000 participants (NCT03332966). Registration activity spans 2003 to 2023.
What does the evidence show for Nicotine in Schizophrenia?
Nicotine has both completed registered trials and synthesis-level publications linked to Schizophrenia. 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 ADRA1A. 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.