Early Adverse Experiences and the Likelihood of Substance Use Disorders and Non-Fatal Overdose in Clinical and Community Settings: A Systematic Review and Meta-Analysis

Early adverse experiences may increase the likelihood of substance use disorders/addictions (SUD) and overdose, but estimates vary across settings. This review synthesised observational evidence on early adverse experiences and disorder-level SUD outcomes and/or non-fatal overdose. PubMed, Scopus, Web of Science, ScienceDirect, SpringerLink, and Taylor & Francis were searched up until 1 December 2025. Eligible observational studies sampled psychiatric treatment or community populations, measured early adverse experiences, and reported associations with disorder-level SUD/addiction or non-fatal overdose. Risk of bias was assessed using Joanna Briggs Institute (JBI) tools. A random-effects meta-analysis pooled commensurate overdose estimates; the remaining evidence was synthesised narratively. Nine studies were included (n = 67,228 participants; one cohort did not report an analytic sample size). SUD associations were consistently positive (adjusted odds ratio (OR) range 1.71–4.30) but were not pooled due to heterogeneity in exposure and outcome definitions. Three studies (721 participants) contributed to the overdose meta-analysis; a higher adverse childhood experience (ACE) score was associated with higher odds of non-fatal overdose (pooled OR 1.16 per +1 ACE, 95% confidence interval (CI) 1.06–1.28; I2 = 28.4%). A Hartung–Knapp sensitivity analysis yielded OR 1.16 (0.95–1.41). Risk of bias was mostly moderate, commonly driven by self-reported outcomes and residual confounding. Early adverse experiences were associated with higher odds of SUD and non-fatal overdose across settings. Limitations include observational designs, variable measurement, and sparse poolable overdose evidence; future studies should distinguish fatal from non-fatal overdose and improve outcome harmonisation.