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Review
. 2025 Nov;120(11):2165-2172.
doi: 10.1111/add.70060. Epub 2025 Apr 8.

Naloxone dosing in the era of synthetic opioids: Applying the Goldilocks principle

Mariana Gonzalez Utrilla  1 , Edward Chesney  1   2 , Joanne Neale  1   3 , Nicola Metrebian  1 , Nicola Kalk  1   2 , Arne Kristian Skulberg  4   5 , Paul Dietze  6   7 , Martin Smith  8 , John Strang  1   2
Affiliations
Review

Naloxone dosing in the era of synthetic opioids: Applying the Goldilocks principle

Mariana Gonzalez Utrilla et al. Addiction. 2025 Nov.

Abstract

The opioid overdose epidemic remains a critical public health crisis. In recent years, synthetic opioids like fentanyl and nitazenes, have driven a sharp rise in deaths. Naloxone, an opioid receptor antagonist, has been established as a key intervention for reversing opioid overdoses and saving lives. However, there remains a critical need to optimize naloxone dosing strategies. This article examines the challenges of both under-dosing and over-antagonism in naloxone administration, emphasizing the importance of a tailored approach to overdose management. A 'just the right dose' approach is essential for minimizing the risks of over-antagonism while still reversing opioid overdose. This involves starting with a modest naloxone dose and carefully titrating it based on the patient's response, considering factors such as opioid type, overdose severity, and opioid tolerance. A tailored approach to naloxone dosing may present challenges for non-medically trained responders but it can ensure that as many people as possible receive the right dose of naloxone when they need it. Training programs should also emphasize the importance of first aid and supportive care, including airway management and alerting emergency services, as well as careful monitoring of the patient's response.

Keywords: naloxone; naloxone dosage; opioid antagonist; opioid overdose; opioid overdose reversal; overdose prevention.

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Conflict of interest statement

M.G.U., E.C., P.D., N.K. and M.S. have no interests to declare. A.K.S. has received two speaker fees (one in 2023 and one in 2024) from Accord Ltd UK, which sells naloxone 1.26 mg/dose in the UK. A.K.S. has no other financial or in‐kind benefits from the sale of any naloxone product. In the last 3 years, J.N. has secured, through her university, research funding from Mundipharma Research Ltd to study the effectiveness of naloxone. Mundipharma developed and market the concentrated naloxone nasal spray, Nyxoid®. J.N. has also secured, through her university, funding from Camurus AB and honoraria from Indivior and Camurus AB for research and presentations unrelated to naloxone. In the last 3 years, N.M. has received, through her university, King’s College London, research funding from Mundipharma Research Ltd, a pharmaceutical company that produces a naloxone nasal spray. Through his employer (King’s College London), J.S. has worked with pharmaceutical and technology companies that have supported the university with grants and/or honoraria and/or consultancy payments, as described at https://www.kcl.ac.uk/people/john-strang (including, in the past 3 years, MundiPharma, Camurus, Pneumowave, Accord and dne), and have also supplied medications or devices (Pneumowave, CMI and Catalent) to develop or study potentially improved formulations and devices. His employer (King’s College London) previously registered intellectual property on an innovative buccal naloxone treatment with which J.S. is involved, and he has previously been named in a patent registration by a Pharma company as the inventor of a concentrated naloxone nasal spray. He is also named as a Patron of Addiction Family Support (formerly DrugFAM), a UK‐based registered charity.

References

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