{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T18:54:52Z","timestamp":1781376892846,"version":"3.54.1"},"posted":{"date-parts":[[2026,4,24]]},"group-title":"Epidemiology","reference-count":80,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Drug overdose deaths in the United States reached record levels during the fentanyl era before recently declining. A plausible hypothesis is that a sudden drop in fentanyl purity (\u201csupply shock\u201d) beginning in 2023 caused the downturn in overdose mortality. We evaluated this hypothesis by replicating a published analysis with regional overdose data, using models that account for time trends and autocorrelation, and negative control indicators to test for spurious correlation. Replicating the original paper, we extracted fentanyl purity data from a figure published by the Drug Enforcement Agency; overdose mortality was derived from standard vital statistics sources. We found that when fentanyl purity was rising, the national purity series did not track overdose increases in most regions and showed only a modest association in the West. When both purity and mortality later declined, the observed associations were also seen with unrelated macroeconomic indicators that shared the same time pattern. Canadian studies revealed variation in both strength and direction of association between fentanyl purity and overdose deaths at sub-province levels. Differential selection bias in law enforcement purity assessment may compromise longitudinal and geographic generalizability of DEA data, notably simulated reporting for higher purity wholesale samples in 2023-4. National fentanyl purity alone does not provide sufficient explanation for the recent decline in overdose deaths. A reduction in localized purity may influence overdose decreases, but other causes must also be considered, including drug supply changes, public health interventions, demographic shifts, behavior changes, inter-cartel dynamics, and fewer new initiates.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Teaser<\/jats:title>\n                  <jats:p>Fentanyl purity alone does not explain the increase and decrease in overdose deaths across all regions of the United States.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.23.26351605","type":"posted-content","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T22:50:16Z","timestamp":1777071016000},"source":"Crossref","is-referenced-by-count":0,"title":["Fentanyl Purity and Overdose Decline: A Reexamination of Geographic Trends"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4098-605X","authenticated-orcid":false,"given":"Nabarun","family":"Dasgupta","sequence":"first","affiliation":[{"name":"University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5073-8677","authenticated-orcid":false,"given":"Adams","family":"Sibley","sequence":"additional","affiliation":[{"name":"University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Gildner","sequence":"additional","affiliation":[{"name":"University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Gora Combs","sequence":"additional","affiliation":[{"name":"University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-3254","authenticated-orcid":false,"given":"Lori A.","family":"Post","sequence":"additional","affiliation":[{"name":"Feinberg School of Medicine, Northwestern University, Evanston, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6051-8950","authenticated-orcid":false,"given":"Sam","family":"Tobias","sequence":"additional","affiliation":[{"name":"School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada"},{"name":"British Columbia Centre on Substance Use, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9092-3671","authenticated-orcid":false,"given":"Alex H.","family":"Kral","sequence":"additional","affiliation":[{"name":"RTI International, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6145-9865","authenticated-orcid":false,"given":"Rosalie Liccardo","family":"Pacula","sequence":"additional","affiliation":[{"name":"Price School of Public Policy, University of Southern California, Los Angeles, California, USA"},{"name":"USC Leonard D. 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