Abstract
BACKGROUND: While many studies have explored the relationship between cannabis and opioid use, few have examined how individuals who use opioids only, cannabis only, or both substances differ in terms of sociodemographic and health-related characteristics. Understanding these differences may support the development of clinical and public health strategies addressing substance use patterns. METHODS: We analyzed data from the 2015-2022 National Survey on Drug Use and Health (NSDUH), focusing on US adults (≥18 years) who reported past-year medical use of prescription opioids and/or cannabis. Individuals were categorized into three mutually exclusive groups: opioid-only, cannabis-only, and opioid-cannabis co-use (OC). Descriptive statistics and weighted multinomial logistic regression models were used to compare characteristics across groups, adjusting for the complex survey design. RESULTS: Among 134,402 adults, 49.5% used opioids only, 35.3% used cannabis only, and 15.2% reported co-use. Co-use was more common among younger adults, individuals with lower income, and those experiencing psychological distress. The impact of depression on the relative risk ratio (RRR) for opioid use only, relative to co-use, was similar to those on the RRR for cannabis use only (RRR = 0.52; 95% CI: 0.49-0.56). However, for many characteristics, the RRR of opioid use only, vs. co-use, differed from that of cannabis use only, vs. co-use. Compared to co-users, individuals in the opioid-only group were more likely to be older, women, and reside in large-metro areas. In contrast, individuals in the cannabis-only group were more likely to be younger, men, report better health status, and reside in non-metro regions. CONCLUSION: Individuals who use opioids only, cannabis only, or both substances differ significantly across demographic, socioeconomic, and health-related factors. These distinctions highlight the need for tailored clinical guidance and public health responses that account for co-use patterns and geographic context to support safer pain management and substance use care.