Academic Journal

Does illicit drug use increase stroke risk? A systematic review, meta-analyses, and Mendelian randomization analysis.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Does illicit drug use increase stroke risk? A systematic review, meta-analyses, and Mendelian randomization analysis.
Συγγραφείς: Ritson M; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK., Markus HS; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK., Harshfield EL; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Πηγή: International journal of stroke : official journal of the International Stroke Society [Int J Stroke] 2026 Jul; Vol. 21 (6), pp. 788-800. Date of Electronic Publication: 2026 Jan 21.
Τύπος έκδοσης: Journal Article; Systematic Review; Meta-Analysis; Review
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: SAGE Publications Country of Publication: United States NLM ID: 101274068 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1747-4949 (Electronic) Linking ISSN: 17474930 NLM ISO Abbreviation: Int J Stroke Subsets: MEDLINE
Imprint Name(s): Publication: 2016- : Thousand Oaks, CA : SAGE Publications
Original Publication: Oxford, UK : Blackwell Pub., c2005-
Ιατρικοί όροι (MeSH): Stroke*/epidemiology , Stroke*/etiology , Stroke*/genetics , Substance-Related Disorders*/complications , Substance-Related Disorders*/epidemiology , Illicit Drugs*/adverse effects, Humans ; Mendelian Randomization Analysis ; Risk Factors
Περίληψη: Background: Epidemiological evidence suggests associations between substance use disorders and risk of stroke, but whether these are due to confounding or are true causal relationships remains uncertain.
Aims: To meta-analyze the observational evidence on illicit substance use and stroke risk and apply Mendelian randomization (MR) to evaluate potential causal effects of substance dependence on stroke subtypes.
Methods: We conducted a systematic review and meta-analysis of studies reporting associations between illicit drug use and stroke (PROSPERO registration-CRD420251053702). The meta-analysis included 32 studies comprising more than 100 million total participants across administrative, hospital-based, and population-based datasets. Pooled odds ratios (ORs) were estimated using multivariate random-effects models for ischemic and hemorrhagic subtypes. We then performed two-sample MR using genome-wide association study summary statistics to examine associations between seven drug exposures and all stroke, ischemic and hemorrhagic stroke, and ischemic stroke subtypes.
Results: Meta-analysis demonstrated significant associations of cannabis (OR = 1.37, 95% confidence interval (95% CI) = 1.14-1.65), cocaine (OR = 1.96; 95% CI = 1.27-3.01), and amphetamines (OR = 2.22, 95% CI = 1.40-3.53) with increased stroke risk, while no significant association was observed for opioids. Findings for cannabis showed some heterogeneity and small-study effects. MR analyses revealed that cannabis use disorder was associated with any stroke (OR = 1.11 [1.01-1.51]) and large artery stroke (OR = 1.35, 95% CI = 1.01-1.80), and cocaine dependence was associated with cardioembolic stroke (OR = 1.08, 95% CI = 1.02-1.14) and intracerebral hemorrhage (OR = 1.38, 95% CI = 1.15-1.65). Genetically predicted substance use disorder overall was associated with any stroke (OR = 1.33, 95% CI = 1.02-1.72) and intracerebral hemorrhage (OR = 7.79, 95% CI = 3.46-17.54). Problematic and dependent alcohol use was linked to large artery and cardioembolic stroke, whereas nicotine dependence showed no significant associations.
Conclusion: Our findings provide consistent observational and genetic evidence that several forms of substance misuse increase stroke risk, particularly cocaine, amphetamines, and cannabis. These findings suggest important public health implications for prevention strategies targeting substance use disorders to mitigate stroke risk.
Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Contributed Indexing: Keywords: Illicit drugs; MR analysis; meta-analysis; stroke; substance-related disorders; systematic review
Substance Nomenclature: 0 (Illicit Drugs)
Entry Date(s): Date Created: 20260122 Date Completed: 20260625 Latest Revision: 20260726
Update Code: 20260726
PubMed Central ID: PMC13291408
DOI: 10.1177/17474930261418926
PMID: 41566428
Βάση Δεδομένων: MEDLINE
FullText Text:
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PubType: Academic Journal
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  Data: Does illicit drug use increase stroke risk? A systematic review, meta-analyses, and Mendelian randomization analysis.
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  Data: <searchLink fieldCode="AU" term="%22Ritson+M%22">Ritson M</searchLink>; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.<br /><searchLink fieldCode="AU" term="%22Markus+HS%22">Markus HS</searchLink>; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.<br /><searchLink fieldCode="AU" term="%22Harshfield+EL%22">Harshfield EL</searchLink>; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
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  Data: <searchLink fieldCode="JN" term="%22101274068%22">International journal of stroke : official journal of the International Stroke Society</searchLink> [Int J Stroke] 2026 Jul; Vol. 21 (6), pp. 788-800. <i>Date of Electronic Publication: </i>2026 Jan 21.
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  Data: Journal Article; Systematic Review; Meta-Analysis; Review
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  Data: English
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22SAGE+Publications%22">SAGE Publications </searchLink><i>Country of Publication: </i>United States <i>NLM ID: </i>101274068 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1747-4949 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2217474930%22">17474930 </searchLink><i>NLM ISO Abbreviation: </i>Int J Stroke <i>Subsets: </i>MEDLINE
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  Data: <i>Publication</i>: 2016- : Thousand Oaks, CA : SAGE Publications<br /><i>Original Publication</i>: Oxford, UK : Blackwell Pub., c2005-
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  Data: <searchLink fieldCode="MM" term="%22Stroke%22">Stroke*</searchLink>/<searchLink fieldCode="MM" term="%22Stroke+epidemiology%22">epidemiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Stroke%22">Stroke*</searchLink>/<searchLink fieldCode="MM" term="%22Stroke+etiology%22">etiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Stroke%22">Stroke*</searchLink>/<searchLink fieldCode="MM" term="%22Stroke+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Substance-Related+Disorders%22">Substance-Related Disorders*</searchLink>/<searchLink fieldCode="MM" term="%22Substance-Related+Disorders+complications%22">complications</searchLink> <br /><searchLink fieldCode="MM" term="%22Substance-Related+Disorders%22">Substance-Related Disorders*</searchLink>/<searchLink fieldCode="MM" term="%22Substance-Related+Disorders+epidemiology%22">epidemiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Illicit+Drugs%22">Illicit Drugs*</searchLink>/<searchLink fieldCode="MM" term="%22Illicit+Drugs+adverse+effects%22">adverse effects</searchLink><br /><searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Mendelian+Randomization+Analysis%22">Mendelian Randomization Analysis</searchLink> ; <searchLink fieldCode="MH" term="%22Risk+Factors%22">Risk Factors</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Epidemiological evidence suggests associations between substance use disorders and risk of stroke, but whether these are due to confounding or are true causal relationships remains uncertain.<br />Aims: To meta-analyze the observational evidence on illicit substance use and stroke risk and apply Mendelian randomization (MR) to evaluate potential causal effects of substance dependence on stroke subtypes.<br />Methods: We conducted a systematic review and meta-analysis of studies reporting associations between illicit drug use and stroke (PROSPERO registration-CRD420251053702). The meta-analysis included 32 studies comprising more than 100 million total participants across administrative, hospital-based, and population-based datasets. Pooled odds ratios (ORs) were estimated using multivariate random-effects models for ischemic and hemorrhagic subtypes. We then performed two-sample MR using genome-wide association study summary statistics to examine associations between seven drug exposures and all stroke, ischemic and hemorrhagic stroke, and ischemic stroke subtypes.<br />Results: Meta-analysis demonstrated significant associations of cannabis (OR = 1.37, 95% confidence interval (95% CI) = 1.14-1.65), cocaine (OR = 1.96; 95% CI = 1.27-3.01), and amphetamines (OR = 2.22, 95% CI = 1.40-3.53) with increased stroke risk, while no significant association was observed for opioids. Findings for cannabis showed some heterogeneity and small-study effects. MR analyses revealed that cannabis use disorder was associated with any stroke (OR = 1.11 [1.01-1.51]) and large artery stroke (OR = 1.35, 95% CI = 1.01-1.80), and cocaine dependence was associated with cardioembolic stroke (OR = 1.08, 95% CI = 1.02-1.14) and intracerebral hemorrhage (OR = 1.38, 95% CI = 1.15-1.65). Genetically predicted substance use disorder overall was associated with any stroke (OR = 1.33, 95% CI = 1.02-1.72) and intracerebral hemorrhage (OR = 7.79, 95% CI = 3.46-17.54). Problematic and dependent alcohol use was linked to large artery and cardioembolic stroke, whereas nicotine dependence showed no significant associations.<br />Conclusion: Our findings provide consistent observational and genetic evidence that several forms of substance misuse increase stroke risk, particularly cocaine, amphetamines, and cannabis. These findings suggest important public health implications for prevention strategies targeting substance use disorders to mitigate stroke risk.
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  Data: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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  Data: <i>Keywords: </i>Illicit drugs; MR analysis; meta-analysis; stroke; substance-related disorders; systematic review
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  Data: 0 (Illicit Drugs)
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  Data: <i>Date Created: </i>20260122 <i>Date Completed: </i>20260625 <i>Latest Revision: </i>20260726
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        Value: 10.1177/17474930261418926
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        Text: English
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        StartPage: 788
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        Type: general
      – SubjectFull: Mendelian Randomization Analysis
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      – SubjectFull: Risk Factors
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      – SubjectFull: Stroke epidemiology
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      – SubjectFull: Stroke etiology
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      – SubjectFull: Stroke genetics
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      – SubjectFull: Substance-Related Disorders epidemiology
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      – SubjectFull: Illicit Drugs adverse effects
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      – TitleFull: Does illicit drug use increase stroke risk? A systematic review, meta-analyses, and Mendelian randomization analysis.
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              Text: 2026 Jul
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              Y: 2026
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