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Abstract: This study examined the relationship between non-substance psychiatric disorders (NSPD) and substance use disorders (SUD) by analyzing patterns of comorbidity across central nervous system (CNS) drug categories using data from Wave 1 of the NESARC (2001-2002). Rather than grouping substances by legal status, drugs were classified by their CNS effects (stimulants, depressants, and analgesics) to better understand potential mechanistic relationships with psychiatric disorders (affective, anxiety, and personality). Analysis of data from 43,093 civilian adults using logistic and multinomial regression revealed that personality disorders showed the strongest associations with substance use overall, particularly with analgesics (OR=2.81). While affective disorders demonstrated moderate but consistent associations across all substance types, anxiety disorders showed relatively weaker relationships. These findings suggest that underlying psychopathology may influence substance use patterns through specific CNS mechanisms, highlighting the importance of considering both psychiatric and neurobiological factors in understanding and treating comorbid conditions.
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