A dynamic model of the opioid drug epidemic with implications for policy.

: The U.S. opioid epidemic has caused substantial harm for over 20 years. Policy interventions have had limited impact and sometimes backfired. Experts recommend a systems modeling approach to address the complexities of opioid policymaking.: Develop a system dynamics simulation model that reflects the complexities and can anticipate intended and unintended intervention effects.: The model was developed from literature review and data gathering. Its outputs, starting in 1990, were compared against 12 historical time series. Four illustrative interventions were simulated for 2020-2030: reducing prescription dosage by 20%, cutting diversion by 30%, increasing addiction treatment from 45% to 65%, and increasing lay naloxone use from 4% to 20%. Sensitivity testing was performed to determine effects of uncertainties. No human subjects were studied.: The model fits historical data well with error percentage averaging 9% across 201 data points. Interventions to reduce dosage and diversion reduce the number of persons with opioid use disorder (PWOUD) by 11% and 16%, respectively, but each of these interventions reduces overdoses by only 1%. Boosting treatment reduces overdoses by 3% but increases PWOUD by 1%. Expanding naloxone reduces overdose deaths by 12% but increases PWOUD by 2% and overdoses by 3%. Combining all four interventions reduces PWOUD by 24%, overdoses by 4%, and deaths by 18%. Uncertainties may affect these numerical results, but policy findings are unchanged.: No single intervention significantly reduces both PWOUD and overdose deaths, but a combination strategy can do so. Entering the 2020s, only protective measures like naloxone expansion could significantly reduce overdose deaths.