Identifiers were verified against the primary record rather than copied from secondary sources. Where we could not verify a figure, we did not publish it, and the list of those is on what is not established.

Chronic pain — scale and incidence

• Dahlhamer J, Lucas J, Zelaya C, Nahin R, Mackey S, DeBar L, Kerns R, Von Korff M, Porter L, Helmick C. Prevalence of chronic pain and high-impact chronic pain among adults — United States, 2016. MMWR Morb Mortal Wkly Rep. 2018;67(36):1001–1006. PMID 30212442. View source.
• Nahin RL, Feinberg T, Kapos FP, Terman GW. Estimated rates of incident and persistent chronic pain among US adults, 2019–2020. JAMA Netw Open. 2023;6(5):e2313563. PMID 37191961. View source.

Prescribing history and policy

• Baker DW. History of The Joint Commission’s pain standards: lessons for today’s prescription opioid epidemic. JAMA. 2017;317(11):1117–1118. PMID 28241189. View source.
• Johnson H, Paulozzi L, Porucznik C, Mack K, Herter B. Decline in drug overdose deaths after state policy changes — Florida, 2010–2012. MMWR Morb Mortal Wkly Rep. 2014;63(26):569–574. PMID 24990490. View source.
• Duensing K, Twillman R, Ziegler S, Cepeda MS, Kern D, Salas M, Wedin G. An examination of state and federal opioid analgesic and continuing education policies: 2016–2018. J Pain Res. 2020;13:2431–2442. PMID 33061558. View source.
• Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain — United States, 2016. MMWR Recomm Rep. 2016;65(1):1–49. PMID 26987082. Simultaneously published as JAMA. 2016;315(15):1624–1645. View source.
• Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC clinical practice guideline for prescribing opioids for pain — United States, 2022. MMWR Recomm Rep. 2022;71(3):1–95. PMID 36327391. View source.

Mortality data

• National Center for Health Statistics. VSRR Provisional Drug Overdose Death Counts (dataset xkb8-kh2a), 12-month-ending counts for the United States. Data accessed 20 August 2026. View source.
• O’Donnell JK, Halpin J, Mattson CL, Goldberger BA, Gladden RM. Deaths involving fentanyl, fentanyl analogs, and U-47700 — 10 states, July–December 2016. MMWR Morb Mortal Wkly Rep. 2017;66(43):1197–1202. PMID 29095804. View source.
• Tanz LJ, Stewart A, Gladden RM, Ko JY, Owens L, O’Donnell J. Detection of illegally manufactured fentanyls and carfentanil in drug overdose deaths — United States, 2021–2024. MMWR Morb Mortal Wkly Rep. 2024;73(48):1099–1105. PMID 39636782. View source.
• Delcher C, Wang Y, Vega RS, et al. Carfentanil outbreak — Florida, 2016–2017. MMWR Morb Mortal Wkly Rep. 2020;69(5):125–129. PMID 32027630. View source.
• Drug Enforcement Administration, Diversion Control Division, Drug & Chemical Evaluation Section. Fentanyl. December 2025. View source.

Dose, metabolism and pharmacogenomics

• Nadeau SE, Wu JK, Lawhern RA. Opioids and chronic pain: an analytic review of the clinical evidence. Front Pain Res. 2021;2:721357. PMID 35295493. View source.
• Crews KR, Monte AA, Huddart R, et al. Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6, OPRM1, and COMT genotypes and select opioid therapy. Clin Pharmacol Ther. 2021;110(4):888–896. PMID 33387367. View source.
• Samer CF, Daali Y, Wagner M, et al. Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety. Br J Pharmacol. 2010;160(4):919–930. PMID 20590588. View source.
• Walter C, Doehring A, Oertel BG, Lötsch J. μ-opioid receptor gene variant OPRM1 118 A>G: a summary of its molecular and clinical consequences for pain. Pharmacogenomics. 2013;14(15):1915–1925. PMID 24236490. View source.
• Jethwa S, Ball M, Langlands K. Pharmacogenomic-guided opioid therapy for pain: a systematic review and meta-analysis of randomised controlled trials. Pharmacogenomics J. 2025;25(4):20. PMID 40651978. View source.
• Cavallari LH, et al. CYP2D6-guided opioid management and postoperative pain control: a randomized clinical trial. JAMA Netw Open. 2026;9(2):e2558299. PMID 41719044. View source.
• Smith DM, et al. Pharmacogenetics to Avoid Loss of Analgesic Effectiveness (PGx-ACT) randomized trial. Clin Transl Sci. 2025;18(2):e70154. PMID 39921243. View source.

Tapering, discontinuation and access

• Agnoli A, Xing G, Tancredi DJ, Magnan E, Jerant A, Fenton JJ. Association of dose tapering with overdose or mental health crisis among patients prescribed long-term opioids. JAMA. 2021;326(5):411–419. PMID 34342618. View source.
• Fenton JJ, Magnan E, Tseregounis IE, Xing G, Agnoli AL, Tancredi DJ. Long-term risk of overdose or mental health crisis after opioid dose tapering. JAMA Netw Open. 2022;5(6):e2216726. PMID 35696163. View source.
• Oliva EM, Bowe T, Manhapra A, Kertesz S, Hah JM, Henderson P, Robinson A, Paik M, Sandbrink F, Gordon AJ, Trafton JA. Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation. BMJ. 2020;368:m283. PMID 32131996. View source.
• Metz VE, Ray GT, Palzes V, et al. Prescription opioid dose reductions and potential adverse events: a multi-site observational cohort study in diverse US health systems. J Gen Intern Med. 2024;39(6):1002–1009. PMID 37930512. View source.
• Perez HR, Buonora M, Cunningham CO, Heo M, Starrels JL. Opioid taper is associated with subsequent termination of care: a retrospective cohort study. J Gen Intern Med. 2020;35(1):36–42. PMID 31428983. View source.
• Lagisetty PA, Healy N, Garpestad C, Jannausch M, Tipirneni R, Bohnert ASB. Access to primary care clinics for patients with chronic pain receiving opioids. JAMA Netw Open. 2019;2(7):e196928. PMID 31298712. View source.
• Carrillo M, Yingst J, Tuan WJ, Giampetro D, Nyland JE, Zgierska AE. Problems accessing pain care, and the adverse outcomes among adults with chronic pain: a cross-sectional survey study. Pain Manag. 2025;15(2):81–91. PMID 39936847. View source.
• Kertesz SG, Gordon AJ. A crisis of opioids and the limits of prescription control: United States. Addiction. 2019;114(1):169–180. PMID 30039595. View source.
• Kertesz SG, Manhapra A, Gordon AJ. Nonconsensual dose reduction mandates are not justified clinically or ethically: an analysis. J Law Med Ethics. 2020;48(2):259–267. PMID 32631183. View source.
• Covington EC, Argoff CE, Ballantyne JC, et al. Ensuring patient protections when tapering opioids: consensus panel recommendations. Mayo Clin Proc. 2020;95(10):2155–2171. PMID 33012347. View source.
• Dickson-Gomez J, Spector A, Weeks M, Galletly C, McDonald M, Green Montaque HD. “You’re not gonna be able to get it”: unintended consequences of prescription drug monitoring programs. Subst Abuse. 2021;15:1178221821992349. PMID 33854323. View source.
• Drug Enforcement Administration. Established Aggregate Production Quotas for Schedule I and II Controlled Substances… for 2025. Final order, Docket No. DEA-1413E. 89 Fed. Reg. 102649 (17 December 2024). View source.
• US Government Accountability Office. Drug Shortages: Better Management of the Quota Process for Controlled Substances Needed; Coordination between DEA and FDA Should Be Improved. GAO-15-202. February 2015. View source.

Risk mitigation, testing and monitoring

• Chou R, Hartung D, Turner J, Blazina I, Chan B, Levander X, McDonagh M, Selph S, Fu R, Pappas M. Opioid Treatments for Chronic Pain. Comparative Effectiveness Review No. 229. AHRQ Publication No. 20-EHC011. Rockville, MD: Agency for Healthcare Research and Quality; April 2020. View source.
• Starrels JL, Becker WC, Alford DP, Kapoor A, Williams AR, Turner BJ. Systematic review: treatment agreements and urine drug testing to reduce opioid misuse in patients with chronic pain. Ann Intern Med. 2010;152(11):712–720. PMID 20513829. View source.
• Snozek CLH, Yee CI, Bryksin J, et al. Assessing knowledge gaps and educational needs in urine drug test interpretation among health care professionals. Am J Clin Pathol. 2025;163(1):69–79. PMID 39066575. View source.
• Saitman A, Park HD, Fitzgerald RL. False-positive interferences of common urine drug screen immunoassays: a review. J Anal Toxicol. 2014;38(7):387–396. PMID 24986836. View source.
• Wanar A, Isley BC, Saia K, Field TA. False-positive fentanyl urine detection after initiation of labetalol treatment for hypertension in pregnancy: a case report. J Addict Med. 2022;16(6):e417–e419. PMID 35972891. View source.
• Fink DS, Schleimer JP, Sarvet A, et al. Association between prescription drug monitoring programs and nonfatal and fatal drug overdoses: a systematic review. Ann Intern Med. 2018;168(11):783–790. PMID 29801093. View source.
• Puac-Polanco V, Chihuri S, Fink DS, Cerdá M, Keyes KM, Li G. Prescription drug monitoring programs and prescription opioid-related outcomes in the United States. Epidemiol Rev. 2020;42(1):134–153. PMID 32242239. View source.
• Wilson MN, Hayden JA, Rhodes E, Robinson A, Asbridge M. Effectiveness of prescription monitoring programs in reducing opioid prescribing, dispensing, and use outcomes: a systematic review. J Pain. 2019;20(12):1383–1393. PMID 31059823. View source.
• Kim B. Must-access prescription drug monitoring programs and the opioid overdose epidemic: the unintended consequences. J Health Econ. 2020;75:102408. PMID 33316762. View source.
• Lee B, Zhao W, Yang KC, Ahn YY, Perry BL. Systematic evaluation of state policy interventions targeting the US opioid epidemic, 2007–2018. JAMA Netw Open. 2021;4(2):e2036687. PMID 33576816. View source.
• Robinson A, Christensen A, Bacon S. From the CDC: the prevention for states program. Meta-analysis of provider use of prescription drug monitoring programs. Pain Med. 2021;22(7):1570–1582. PMID 33484144. View source.

Diversion

• Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. Key Substance Use and Mental Health Indicators in the United States: Results from the 2024 National Survey on Drug Use and Health. HHS Publication No. PEP25-07-007, NSDUH Series H-60. July 2025. View source.
• Jones CM, Paulozzi LJ, Mack KA. Sources of prescription opioid pain relievers by frequency of past-year nonmedical use: United States, 2008–2011. JAMA Intern Med. 2014;174(5):802–803. PMID 24589763. View source.
• Han B, Compton WM, Blanco C, Crane E, Lee J, Jones CM. Prescription opioid use, misuse, and use disorders in U.S. adults: 2015 National Survey on Drug Use and Health. Ann Intern Med. 2017;167(5):293–301. PMID 28761945. View source.
• McDonald DC, Carlson KE. Estimating the prevalence of opioid diversion by “doctor shoppers” in the United States. PLoS One. 2013;8(7):e69241. PMID 23874923. View source.
• US Government Accountability Office. Prescription Drug Control: DEA Has Enhanced Efforts to Combat Diversion, but Could Better Assess and Report Program Results. GAO-11-744. August 2011. View source.
• Schaefer MK, Perz JF. Outbreaks of infections associated with drug diversion by US health care personnel. Mayo Clin Proc. 2014;89(7):878–887. PMID 24933292. View source.
• Alroy-Preis S, Daly ER, Adamski C, et al. Large outbreak of hepatitis C virus associated with drug diversion by a healthcare technician. Clin Infect Dis. 2018;67(6):845–853. PMID 29767683. View source.
• Warner DO, Berge K, Sun H, Harman A, Hanson A, Schroeder DR. Substance use disorder among anesthesiology residents, 1975–2009. JAMA. 2013;310(21):2289–2296. PMID 24302092. View source.
• Wilton J, Wong S, Purssell R, et al. Association between prescription opioid therapy for noncancer pain and hepatitis C virus seroconversion. JAMA Netw Open. 2022;5(1):e2143050. PMID 35019983. View source.

Social determinants

• National Academies of Sciences, Engineering, and Medicine. Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use. Bonnie RJ, Ford MA, Phillips JK, editors. Washington, DC: The National Academies Press; 2017. View source.
• Altekruse SF, Cosgrove CM, Altekruse WC, Jenkins RA, Blanco C. Socioeconomic risk factors for fatal opioid overdoses in the United States: findings from the Mortality Disparities in American Communities Study (MDAC). PLoS One. 2020;15(1):e0227966. PMID 31951640. View source.
• Dube SR, Felitti VJ, Dong M, Chapman DP, Giles WH, Anda RF. Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: the adverse childhood experiences study. Pediatrics. 2003;111(3):564–572. PMID 12612237. View source.
• Stein MD, Conti MT, Kenney S, et al. Adverse childhood experience effects on opioid use initiation, injection drug use, and overdose among persons with opioid use disorder. Drug Alcohol Depend. 2017;179:325–329. PMID 28841495. View source.
• Fine DR, Dickins KA, Adams LD, et al. Drug overdose mortality among people experiencing homelessness, 2003 to 2018. JAMA Netw Open. 2022;5(1):e2142676. PMID 34994792. View source.
• Hollingsworth A, Ruhm CJ, Simon K. Macroeconomic conditions and opioid abuse. J Health Econ. 2017;56:222–233. PMID 29128677. View source.
• Case A, Deaton A. Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century. PNAS. 2015;112(49):15078–15083. PMID 26575631. View source.
• Masters RK, Tilstra AM, Simon DH. Explaining recent mortality trends among younger and middle-aged White Americans. Int J Epidemiol. 2018;47(1):81–88. PMID 29040539. View source.
• Ruhm CJ. Drivers of the fatal drug epidemic. J Health Econ. 2019;64:25–42. PMID 30784811. View source.
• Ruhm CJ. Mental health and mortality trends in the United States. J Health Econ. 2025;102:103015. PMID 40466290. View source.