Abstract
Objectives. To characterize present-day polysubstance use patterns in the general adult population. Methods. From a 2022 nationally representative survey in the United States, we defined polysubstance use as last 12-month use of 2 or more drugs (n = 15 800). Latent class analyses included medical (as indicated) and nonmedical (not as directed) use of prescription opioids, stimulants, benzodiazepines, and antidepressants; recreational use of cannabis, psilocybin or mushrooms, other psychedelics, cocaine, methamphetamine, and illicit opioids; and concomitant use with alcohol, cannabis, prescriptions, or recreational drugs. Results. The national prevalence of polysubstance use was 20.9% (95% confidence interval = 20.5%, 21.3%), broken down into the following 4 latent classes: (1) medically guided polysubstance use (11.5% prevalence, 6.1% substance use disorder [SUD]): prescribed drug use, some cannabis, and no concomitant use; (2) principal cannabis use variety (4.0% prevalence, 31.9% SUD): high probability of cannabis use with various drugs concomitantly used; (3) self-guided polysubstance use (3.4% prevalence, 14.5% SUD): nonmedical use of prescriptions and concomitant use; and (4) indiscriminate coexposures (2.1% prevalence, 58.9% SUD): concomitant drug use with indiscriminate drug preference. Conclusions. Different polysubstance profiles show adults with untreated SUDs, and there are 2 previously unrecognized classes. Prevention and treatment strategies addressing polysubstance use should take a personalized perspective and tailor to individuals' use profile. (Am J Public Health. 2025;115(5):747-757. https://doi.org/10.2105/AJPH.2024.307979).