Importance: With the implementation of Measure 110 (M110), Oregon became the first state in the United States to decriminalize personal possession of all drugs. No analysis of the effect of this law on overdose mortality has fully accounted for the introduction of fentanyl to Oregon's unregulated drug market, a substance known to drive fatal overdose rates. Objective: To evaluate whether the decriminalization of drug possession in Oregon was associated with changes in fatal drug overdose rates after accounting for the timing and spread of fentanyl through Oregon's unregulated drug market. Design, Setting, and Participants: The association between fatal drug overdose and enactment of M110 in Oregon was analyzed using a matrix completion synthetic control method. The synthetic control unit was imputed from the 48 US states and Washington DC that did not decriminalize drugs. The rapid escalation of fentanyl in unregulated drug markets was determined using the state-level percentage of all samples reported to the National Forensic Laboratory Information System that were identified as fentanyl or its analogs. A changepoint analysis was used to determine when each state experienced a rapid escalation of fentanyl in its unregulated drug market. Mortality data were obtained from the Centers for Disease Control and Prevention from 2008-2022. Exposures: M110 took effect on February 1, 2021. Main Outcome: Fatal drug overdose rates per half-year. Results: Analysis indicated a rapid escalation of fentanyl in Oregon's unregulated drug supply occurred in the first half of 2021, contemporaneous with the enactment of M110. The crude association between decriminalization and fatal overdose rate per 100,000 per half-year was significant (Tau = 1.83; SE = 0.39; p < 0.001); however, adjusting for the rapid escalation of fentanyl as a confounder, the effect of drug decriminalization on overdose mortality in Oregon was null (Tau = -0.51; SE = 0.36). Sensitivity analyses were consistent with this result. Conclusions and Relevance: After adjusting for the rapid escalation of fentanyl, analysis found no association between M110 and fatal drug overdose rates. Future evaluations of the health effects of drug policies should account for confounding changes in the composition and potency of unregulated drug markets.

The authors have declared no competing interest.

This study was funded in part by the National Institute on Drug Abuse (K01DA056654 to Dr. del Pozo) and Arnold Ventures (grant funding to Drs. Kral and Lambdin). These organizations had no role in the conduct of the study, nor the preparation of this manuscript, and the findings and opinions expressed do not necessarily reflect their views or positions.

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The source data were publicly available prior to the initiation of our study. They are available for download from the Centers for Disease Control and Prevention, and the US Drug Enforcement Administration's National Forensic Laboratory Information System, via their websites: https://wonder.cdc.gov/ and https://www.nflis.deadiversion.usdoj.gov/

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