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amphetamines (including amphetamine and methamphetamine) has been consistently associated with mental health difficulties; however, the direction of potential causal relationships has not yet been established. This study aimed to assess the direction relationships between illicit amphetamine use and mental health difficulties across adolescence and young adulthood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Observational study of four population\u2010level cohorts participating in the Monitoring Illicit Substance Use (MISUse) Consortium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Australia and New Zealand.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>A total of 7527 participants (51% female) were used: Christchurch Health and Development Study (<jats:italic>n<\/jats:italic>\u2009=\u20091056), Australian Temperament Project (<jats:italic>n<\/jats:italic>\u2009=\u20091644), Victorian Adolescent Health Cohort Study (<jats:italic>n<\/jats:italic>\u2009=\u20091943) and International Youth Development Study (<jats:italic>n<\/jats:italic>\u2009=\u20092884).<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements<\/jats:title><jats:p>Assessments were used to derive binary indicators of amphetamine use (\u2265monthly) and mental health difficulties during both adolescence (age 10\u201317\u2009years) and young adulthood (age 18\u201330\u2009years).<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>Associations were estimated as Risk Ratios (RRs) with 95% confidence internals (CIs) using G\u2010computation procedures, while accounting for 15 potential confounding factors and interactions between exposure and both study cohort and participant sex. The risk of mental health difficulties in young adulthood was 21% greater (RR\u2009=\u20091.21, 95% CI\u2009=\u20091.04, 1.41) for those who reported monthly or more frequent amphetamine use in adolescence. The risk of monthly or higher amphetamine use in young adulthood was 19% greater (RR\u2009=\u20091.19, 95% CI\u2009=\u20090.99, 1.45) in those who reported mental health difficulties in adolescence. There was also some evidence to suggest that in males the strongest association was from amphetamine use to mental health difficulties (RR\u2009=\u20091.24, 95% CI\u2009=\u20090.95, 1.60), while in females the strongest association was from mental health difficulties to amphetamine use (RR\u2009=\u20091.33, 95% CI\u2009=\u20090.99, 1.78).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>There appears to be a bidirectional association between monthly or more frequent amphetamine use and mental health difficulties from adolescence to young adulthood.<\/jats:p><\/jats:sec>","DOI":"10.1111\/add.70033","type":"journal-article","created":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T09:23:57Z","timestamp":1742030637000},"page":"1623-1633","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Amphetamine use and mental health difficulties across adolescence and young adulthood: An integrative 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