Fentanyl

ImportanceBuprenorphine treatment of opioid use disorder (OUD) is safe and effective, but opioid withdrawal during treatment initiation is associated with poor retention in care. As fentanyl has replaced heroin in the drug supply, case reports and surveys have indicated increased concern for buprenorphine-precipitated withdrawal (PW); however, some observational studies have found a low incidence of PW.ObjectiveTo estimate buprenorphine PW incidence and assess factors associated with PW among emergency department (ED) or hospitalized patients.Design, setting, and participantsThis retrospective cohort study at 3 academic hospitals in Philadelphia, Pennsylvania, included adults with OUD who underwent traditional or high-dose buprenorphine initiation between January 1, 2020, and December 31, 2021. Exclusion criteria included low-dose buprenorphine initiation and missing documentation of opioid withdrawal severity within 4 hours of receiving buprenorphine.ExposureBuprenorphine initiation with an initial dose of at least 2 mg of sublingual buprenorphine after a Clinical Opiate Withdrawal Scale (COWS) score of 8 or higher. Additional exposures included 4 predefined factors potentially associated with PW: severity of opioid withdrawal before buprenorphine (COWS score of 8-12 vs ≥13), initial buprenorphine dose (2 vs 4 or ≥8 mg), body mass index (BMI) (Main outcome and measuresThe main outcome was PW incidence, defined as a 5-point or greater increase in COWS score from immediately before to within 4 hours after buprenorphine initiation. Logistic regression was used to estimate the odds of PW associated with the 4 aforementioned predefined factors.ResultsThe cohort included 226 patients (150 [66.4%] male; mean [SD] age, 38.6 [10.8] years). Overall, 26 patients (11.5%) met criteria for PW. Among patients with PW, median change in COWS score was 9 points (IQR, 6-13 points). Of 123 patients with confirmed fentanyl use, 20 (16.3%) had PW. In unadjusted and adjusted models, BMI of 30 or greater compared with less than 25 (adjusted odds ratio [AOR], 5.12; 95% CI, 1.31-19.92) and urine fentanyl concentration of 200 ng/mL or greater compared with less than 20 ng/mL (AOR, 8.37; 95% CI, 1.60-43.89) were associated with PW.Conclusions and relevanceIn this retrospective cohort study, 11.5% of patients developed PW after buprenorphine initiation in ED or hospital settings. Future studies should confirm the rate of PW and assess whether bioaccumulated fentanyl is a risk factor for PW.

ImportanceWith the implementation of Measure 110 (M110) in 2021, Oregon became the first US state to decriminalize small amounts of any drug for personal use. To date, no analysis of the association of this law with overdose mortality has fully accounted for the introduction of fentanyl-a substance that is known to drive fatal overdose-to Oregon's unregulated drug market.ObjectiveTo evaluate whether the decriminalization of drug possession in Oregon was associated with changes in fatal drug overdose rates after accounting for the rapid spread of fentanyl in Oregon's unregulated drug market.Design, setting, and participantsIn this cohort study, the association between fatal overdose and enactment of M110 was analyzed using a matrix completion synthetic control method. The control group consisted of the 48 US states and Washington, DC, all of which did not decriminalize drugs. The rapid spread 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 analogues. Mortality data were obtained from the Centers for Disease Control and Prevention for January 1, 2008, to December 31, 2022. Data analysis was performed from fall 2023 through spring 2024.ExposuresMeasure 110 took effect in Oregon on February 1, 2021.Main outcomes and measuresThe primary outcome assessed was fatal drug overdose rates per half-year. A changepoint analysis also determined when each state experienced a rapid escalation of fentanyl in its unregulated drug market.ResultsIn this analysis, rapid spread of fentanyl in Oregon's unregulated drug supply occurred in the first half of 2021, contemporaneous with enactment of M110. A positive crude association was found between drug decriminalization and fatal overdose rate per 100 000 per half year (estimate [SE], 1.83 [0.47]; P Conclusions and relevanceIn this cohort study of fatal drug overdose and the spread of fentanyl through Oregon's unregulated drug market, no association between M110 and fatal overdose rates was observed. Future evaluations of the health effects of drug policies should account for changes in the composition of unregulated drug markets.

ImportanceIllegal fentanyl is driving overdose mortality, and fentanyl test strips (FTS) can be used to test drugs for fentanyl at the point of consumption. Evidence on whether FTS use is associated with overdose risk reduction behaviors is encouraging, but largely limited to smaller, single-site studies.ObjectiveTo determine whether self-reported baseline FTS use among people who use drugs (PWUD) was associated with overdose risk reduction behaviors and nonfatal overdose over a 28-day follow-up.Design, setting, and participantsMultisite, observational cohort study of PWUD conducted from May to December 2023 as an ancillary study of the HEALing Communities Study, which consists of fixed and mobile direct service provision sites in 14 community partner organizations distributing FTS. Participants lived in Kentucky, New York, or Ohio and reported using heroin, fentanyl, cocaine, methamphetamine, or nonprescribed opioids, benzodiazepines, or stimulants within 30 days before baseline. Participants were followed up for a maximum of 37 days.ExposureBaseline FTS use.Main outcome and measuresThe primary outcome was a composite score measuring the self-reported number and frequency of using 8 overdose risk reduction behaviors. Secondary outcomes included multiple measures (eg, self-reported nonfatal overdose).ResultsThe study included 732 participants (median [IQR] age, 41 [34.0-48.0] years; 369 [50.4%] male; 64 [8.9%] Black or African American, 587 [81.3%] White, and 71 [9.8%] other races); 414 reported baseline FTS use and 318 did not. Compared with nonusers, a higher percentage of baseline FTS users were from Ohio and White, while a lower percentage were from New York and Hispanic and/or Black. In adjusted analyses, PWUD who used FTS had a mean daily composite score for overdose risk reduction behaviors that was 0.86 (95% CI, 0.34-1.38) units higher across follow-up compared with nonusers (score for FTS users, 7.37; nonusers, 6.51). There was no difference in self-reported nonfatal overdoses between the 2 groups (mean daily risk for FTS users, 0.02; nonusers, 0.02; risk ratio, 1.20; 95% CI, 0.70-2.06).Conclusions and relevanceIn this cohort study, baseline FTS use was associated with greater engagement in overdose risk reduction behaviors during follow-up, but not with the risk of nonfatal overdose during follow-up, suggesting PWUD who use FTS may also engage in a broader set of harm reduction strategies.

ImportanceThe monthly opioid overdose death rate in the US has declined by 50% from its peak in the summer of 2023 through fall of 2024, and the factors associated with this decline are not fully understood.ObjectiveTo examine the association between the proportion of fentanyl reports in illicit drug seizures and opioid overdose deaths during periods of rising and falling mortality.Design and settingThis secondary analysis of state-month level panel data from the National Forensic Laboratory Information System and US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) was conducted from January 2018 to September 2024 and included all 50 US states and Washington, DC. CDC WONDER data were collected from recorded death certificates; National Forensic Laboratory Information System data were obtained from drug reports submitted by forensic laboratories. The data were analyzed from July to August 2025.ExposurePercentage of illicit drug seizures that contained fentanyl or fentanyl-related compounds. Illicit drug seizures were defined as seizures that contained any of the following: fentanyl or fentanyl-related compounds, heroin, methamphetamine, cocaine, and xylazine.Main outcomes and measuresThe monthly count of opioid overdose deaths, given by uniform claim descriptor codes X40 to 44, X60 to 64, X85, and Y10 to Y14, with additional multiple cause of death codes of T40.0 to 4 and T40.6. Death rates were calculated using yearly population estimates from the American Community Survey.ResultsFrom a peak in the summer of 2023 through the fall of 2024, the monthly opioid overdose death rate declined by 50%, from 2.2 to 1.1 per 100 000. This decline was was accompanied by a decline in the fentanyl reports as a proportion of total illicit drug seizures from 28.8% to 23.2%. In a 2-way, fixed-effects model, a 1-percentage point reduction in fentanyl prevalence was associated with 0.018 fewer overdose deaths per 100 000 population per month (95% CI, 0.016-0.019; P Conclusions and relevanceThe study results suggest that current decline in the proportion of fentanyl reports in illicit drug seizures is associated with 9.2% of the total observed decline in mortality. Additional contributing factors may include other shifts in the drug supply not captured by fentanyl prevalence in illicit drug seizures, shifts in drug use behavior, and the effect of public health programs, interventions, and policies.