Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators int he United States: results from the 2024 National Survey on Drug Use and Health (HHS Publication No. PEP25-07-007, NSDUH Series H-60). Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. Rockville: Substance Abuse and Mental Health Services Administration; 2025. p. 1–132. https://www.samhsa.gov/data/data-we-collect/nsduh-national-survey-drug-use-and-health/national-releases.

Naghavi M, Kyu HH, Bhoomadevi A, Aalipour MA, Aalruz H, Ababneh HS, et al. Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990–2023: a systematic analysis for the Global Burden of Disease Study 2023. Lancet. 2025;406(10513):1811–72. https://doi.org/10.1016/S0140-6736(25)01917-8.

Article  Google Scholar 

Colledge-Frisby S, Ottaviano S, Webb P, Grebely J, Wheeler A, Cunningham EB, et al. Global coverage of interventions to prevent and manage drug-related harms among people who inject drugs: a systematic review. Lancet Glob Health. 2023;11(5):e673–83. https://doi.org/10.1016/S2214-109X(23)00058-X.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Volkow ND, Icaza MEM-M, Poznyak V, Saxena S, Gerra G, Network tU-WIS. Addressing the opioid crisis globally. World Psychiatry. 2019;18(2):231–2. https://doi.org/10.1002/wps.20633.

Article  PubMed Central  PubMed  Google Scholar 

Strang J, Volkow ND, Degenhardt L, Hickman M, Johnson K, Koob GF, et al. Opioid use disorder. Nat Rev Dis Primers. 2020;6(1):3. https://doi.org/10.1038/s41572-019-0137-5.

Article  PubMed  Google Scholar 

Selley DE, Liu Q, Childers SR. Signal transduction correlates of mu opioid agonist intrinsic efficacy: receptor-stimulated [35S]GTPγS binding in mMOR-CHO cells and rat thalamus. J Pharmacol Exp Ther. 1998;285(2):496–505. https://doi.org/10.1016/S0022-3565(24)37462-2.

Article  CAS  PubMed  Google Scholar 

Livingston KE, Mahoney JP, Manglik A, Sunahara RK, Traynor JR. Measuring ligand efficacy at the mu-opioid receptor using a conformational biosensor. Elife. 2018;7:e32499. https://doi.org/10.7554/eLife.32499.

Article  PubMed Central  PubMed  Google Scholar 

WHO Expert Committee on the Selective and Use of Essential Medicines. The selection and use of essential medicines: report of the WHO Expert Committee. 14th ed. Geneva: WHO; 2005.

Google Scholar 

van den Brink W, Hendriks VM, Blanken P, Koeter MWJ, van Zwieten BJ, van Ree JM. Medical prescription of heroin to treatment resistant heroin addicts: two randomised controlled trials. BMJ. 2003;327(7410):310. https://doi.org/10.1136/bmj.327.7410.310.

Article  PubMed Central  PubMed  Google Scholar 

Oviedo-Joekes E, Brissette S, Marsh DC, Lauzon P, Guh D, Anis A, et al. Diacetylmorphine versus methadone for the treatment of opioid addiction. N Engl J Med. 2009;361(8):777–86. https://doi.org/10.10156/NEJM0810635.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Milella MS, D’Ottavio G, De Pirro S, Barra M, Caprioli D, Badiani A. Heroin and its metabolites: relevance to heroin use disorder. Transl Psychiatry. 2023;13(1):120. https://doi.org/10.1038/s41398-023-02406-5.

Article  PubMed Central  PubMed  Google Scholar 

Rahimi-Movaghar A, Gholami J, Amato L, Hoseinie L, Yousefi-Nooraie R, Amin-Esmaeili M. Pharmacological therapies for management of opium withdrawal. Cochrane Database Syst Rev. 2018. https://doi.org/10.1002/14651858.CD007522.pub2.

Article  PubMed Central  PubMed  Google Scholar 

Kuszmaul AK, Palmer EC, Frederick EK. Lofexidine versus clonidine for mitigation of opioid withdrawal symptoms: a systematic review. J Am Pharm Assoc. 2020;60(1):145–52. https://doi.org/10.1016/j.japh.2019.10.004.

Article  Google Scholar 

Bell J, Strang J. Medication treatment of opioid use disorder. Biol Psychiatry. 2020;87(1):82–8. https://doi.org/10.1016/j.biopsych.2019.06.020.

Article  CAS  PubMed  Google Scholar 

Perry D, Kirkwood JEM, Doroshuk ML, Kelmer M, Korownyk CS, Ton J, et al. Opioid agonist therapy for opioid use disorder in primary versus specialty care. Cochrane Database Syst Rev. 2025. https://doi.org/10.1002/14651858.CD013672.pub2.

Article  PubMed Central  PubMed  Google Scholar 

Bremer W, Plaisance K, Walker D, Bonn M, Love JS, Perrone J, et al. Barriers to opioid use disorder treatment: a comparison of self-reported information from social media with barriers found in literature. Front Public Health. 2023. https://doi.org/10.3389/fpubh.2023.1141093.

Article  PubMed Central  PubMed  Google Scholar 

Nielsen S, Tse WC, Larance B. Opioid agonist treatment for people who are dependent on pharmaceutical opioids. Cochrane Database Syst Rev. 2022. https://doi.org/10.1002/14651858.CD011117.pub3.

Article  PubMed Central  PubMed  Google Scholar 

Banks ML, Townsend EA, Negus SS. Testing the 10 most wanted: a preclinical algorithm to screen candidate opioid use disorder medications. Neuropsychopharmacology. 2019;44:1011–2. https://doi.org/10.1038/s41386-019-0336-5.

Article  PubMed Central  PubMed  Google Scholar 

Rasmussen K, White DA, Acri JB. NIDA’s medication development priorities in response to the opioid crisis: ten most wanted. Neuropsychopharmacology. 2019;44(4):657–9. https://doi.org/10.1038/s41386-018-0292-5.

Article  PubMed  Google Scholar 

Venniro M, Banks ML, Heilig M, Epstein DH, Shaham Y. Improving translation of animal models of addiction and relapse by reverse translation. Nat Rev Neurosci. 2020;21:625–43. https://doi.org/10.1038/s41583-020-0378-z.

Article  CAS  PubMed  Google Scholar 

Townsend EA, Negus SS, Banks ML. Medications development for treatment of opioid use disorder. Cold Spring Harb Perspect Med. 2021;11(1):a039263. https://doi.org/10.1101/cshperspect.a039263.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Spragg SDS. Morphine addiction in Chimpanzees. Comparative psychology monographs. Baltimore: The John Hopkins Press; 1940. p. 1–132.

Google Scholar 

Griffiths RR, Wurster RM, Brady JV. Discrete-trial choice procedure: effects of naloxone and methadone on choice between food and heroin. Pharmacol Rev. 1975;27(3):357–65.

Article  CAS  PubMed  Google Scholar 

Negus SS. Choice between heroin and food in nondependent and heroin-dependent Rhesus monkeys: effects of naloxone, buprenorphine, and methadone. J Pharmacol Exp Ther. 2006;317(2):711–23. https://doi.org/10.1124/jpet.105.095380.

Article  CAS  PubMed  Google Scholar 

Mello NK, Negus SS. Preclinical evaluation of pharmacotherapies for treatment of cocaine and opioid abuse using drug self-administration procedures. Neuropsychopharmacology. 1996;14(6):375–424. https://doi.org/10.1016/0893-133X(95)00274-H.

Article  CAS  PubMed  Google Scholar 

Haney M, Spealman R. Controversies in translational research: drug self-administration. Psychopharmacology. 2008;199(3):403–19. https://doi.org/10.1007/s00213-008-1079-x.

Article  CAS  PubMed Central  PubMed  Google Scholar 

Heyman GH. Addiction: a disorder of choice. Cambridge: Harvard University Press; 2009.

Book  Google Scholar 

Ahmed SH. Validation crisis in animal models of drug addiction: beyond non-disordered drug use toward drug addiction. Neurosci Biobehav Rev. 2010;35(2):172–84. https://doi.org/10.1016/j.neubiorev.2010.04.00529.

Article  CAS  PubMed  Google Scholar 

Banks ML, Negus SS. Preclinical determinants of drug choice under concurrent schedules of drug self-administration. Adv Pharmacol Sci. 2012;2012:281768. https://doi.org/10.1155/2012/281768.

Article  PubMed Central  PubMed  Google Scholar 

Acuff SF, MacKillop J, Murphy JG. A contextualized reinforcer pathology approach to addiction. Nat Rev Psychol. 2023;2(5):309–23. https://doi.org/10.1038/s44159-023-00167-y.

Article  PubMed Central  PubMed  Google Scholar 

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