Opioid use disorder


Opioid use disorder (OUD) is a chronic relapsing disorder that, whilst initially driven by activation of brain reward neurocircuits, increasingly engages anti-reward neurocircuits that drive adverse emotional states and relapse. However, successful recovery is possible with appropriate treatment, although with a persisting propensity to relapse. The individual and public health burdens of OUD are immense; 26.8 million people were estimated to be living with OUD globally in 2016, with >100,000 opioid overdose deaths annually, including >47,000 in the USA in 2017. Well-conducted trials have demonstrated that long-term opioid agonist therapy with methadone and buprenorphine have great efficacy for OUD treatment and can save lives. New forms of the opioid receptor antagonist naltrexone are also being studied. Some frequently used approaches have less scientifically robust evidence but are nevertheless considered important, including community preventive strategies, harm reduction interventions to reduce adverse sequelae from ongoing use and mutual aid groups. Other commonly used approaches, such as detoxification alone, lack scientific evidence. Delivery of effective prevention and treatment responses is often complicated by coexisting comorbidities and inadequate support, as well as by conflicting public and political opinions. Science has a crucial role to play in informing public attitudes and developing fuller evidence to understand OUD and its associated harms, as well as in obtaining the evidence today that will improve the prevention and treatment interventions of tomorrow.

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Fig. 1: Age-standardized prevalence of OUD per 100,000 people.
Fig. 2: Opioid prescriptions and deaths.
Fig. 3: Age-standardized DALYs due to OUD.
Fig. 4: Conceptual framework for the neurobiological basis of addiction and vulnerability.
Fig. 5: Acute actions of drugs of abuse on the VTA and NAc.
Fig. 6: Hypothetical neurocircuitry for the negative emotional states associated with the withdrawal/negative affect stage.
Fig. 7: Role of the PFC in initiating and inhibiting the reinstatement of drug-seeking behaviour.
Fig. 8: Model projections of the effect of various treatments on transmission of HCV in people with OUD.
Fig. 9: Schematic of treatment algorithm.


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The authors acknowledge M. Bela at King’s College London for enduring patience with manuscript preparation and M. Krieger at Brown University for his research assistance. J.S. and M.H. acknowledge UK NIHR Senior Investigator grants. J.S. is supported by the NIHR Biomedical Research Centre for Mental Health at South London & Maudsley NHS Foundation Trust and King’s College London. B.D.L.M. is supported in part by the US National Institute of General Medical Sciences (P20GM125507).

Author information




Introduction (J.S. and N.D.V.); Epidemiology (L.D. and B.D.L.M.); Mechanisms/pathophysiology (G.F.K. and N.D.V.); Diagnosis, screening and prevention (M.H. and M.T.); Management (S.L.W. and J.S.); Quality of life (K.J.); Outlook (J.S. and N.D.V.); Overview of Primer (J.S. and N.D.V.). After the joint first authors, all authors are listed alphabetically, and all contributed significantly to the assigned sections.

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Correspondence to John Strang or Nora D. Volkow.

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J.S.’s employer (King’s College London) has received, connected to his work, project grant support and/or honoraria and/or consultancy payments from the UK Department of Health, Public Health England, and the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) as well as research grants from (past 3 years) the UK National Institute for Health Research (NIHR), the Medical Research Council and the Pilgrim Trust. J.S. has also worked with the EMCDDA, United Nations Office on Drugs and Crime, US FDA and US National Institute on Drug Abuse (NIDA), and WHO as well as with other international government agencies. King’s College London has registered intellectual property on a buccal naloxone with which J.S. is involved, and J.S. has been named in a patent registration by MundiPharma as inventor of a potential concentrated naloxone nasal spray. King’s College London has also received, connected to the work of J.S., research grant support and/or payment of honoraria, consultancy payments, and/or travelling, accommodation and/or conference expenses (past 3 years) from Braeburn, Camurus, Indivior, Molteni Farma and MundiPharma, and has received trial medication supplies from Braeburn and iGen related to medications and technologies potentially applicable in the treatment of addictions and related problems. J.S. has worked with and received grant support from the charity Action on Addiction and with the Pilgrim Trust and is a Patron of DrugFAM. L.D. has received investigator-initiated untied educational grants for studies of opioid medications in Australia from Indivior, MundiPharma and Seqirus. The Australian National Drug and Alcohol Research Centre of the University of New South Wales Sydney is supported by funding from the Australian Government Department of Health under the Drug and Alcohol Program. L.D. is supported by an Australian National Health and Medical Research Council Senior Principal Research Fellowship (#1041742, #1135991) and by US National Institutes of Health grant NIDA (R01DA1104470). M.H. has received unrestricted honoraria for presenting at scientific meetings within the past 2 years from Gilead and MSD, and acknowledges support from the NIHR Public Health and Prevention in Evaluation, NIHR School for Public Health Research and NIHR Biomedical Research Centre at Bristol. In the past year, K.J. has received funding from Johnson, Bassin and Shaw to conduct analysis of Medicare data for assessment of opioid use for a Medicare contractor. She has a subcontract to NIDA (grant no. DA035789) to write a paper on the results of a clinical trial on a mobile app to address substance use disorders. She has consulted several times for AlphaSights on opioid issues for their clients, who cannot be disclosed but are not pharmaceutical companies, pharmacies or other entities currently engaged in the industry. K.J. is the Executive Director of the International Consortium of Universities for Drug Demand Reduction, which is registered as a not-for-profit organization in the USA and is funded by the US Department of State. K.J. declares that, for the period prior, she was employed by the US government. S.L.W.’s employer, University of Kentucky, has received research support related to her work from the Braeburn Pharmaceuticals, US FDA and US NIDA (in the past 3 years). S.L.W. has worked with the FDA, NIDA, NIH and WHO on issues related to substance use disorders and opioid abuse liability; has served as a scientific advisory board member for the Addiction Policy Forum, the NIDA Scientific Advisory Council and Opiant Pharmaceuticals; and has received, connected to her work, research grant support and/or payment of honoraria, consultancy payments and/or travelling, accommodation and/or conference expenses from pharmaceutical/device companies (over the past 3 years) from Brainsway, Braeburn, Camurus, Eli Lilly and Co., Indivior, Neurocrine, Otsuka, Pfizer, Summit Biosciences, Trevi Pharmaceuticals and U.S. World Meds. All other authors declare no competing interests.

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Strang, J., Volkow, N.D., Degenhardt, L. et al. Opioid use disorder. Nat Rev Dis Primers 6, 3 (2020). https://doi.org/10.1038/s41572-019-0137-5

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