Does illicit drug use increase stroke risk? A systematic review, meta-analyses, and Mendelian randomization analysis
Year: 2026
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: 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.
Source: International Journal of Stroke
Authors: Megan Ritson, Hugh S Markus, Eric L Harshfield
Institution: University of Cambridge
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,400
Funders: Alzheimer's Society, Alzheimer Society, National Institute for Health and Care Research, British Heart Foundation, Department of Health and Social Care, University of Cambridge, Cambridge University Hospitals, NIHR Cambridge Biomedical Research Centre, Cambridge BHF Centre of Research Excellence
OpenAlex ID: W7125428320