How and why does naloxone save lives? A realist review of what works and why

What is it about?

Naloxone is a medication that reverses opioid overdose and is central to harm reduction responses to the drug-related death crisis, yet previous systematic reviews had established only that it works, not how or why. This realist review, pre-registered on PROSPERO and conducted to RAMESES standards, analysed 55 relevant outputs across study designs to develop programme theory explaining the mechanisms and contexts that make naloxone-based interventions effective. The review produced two middle-range theories: Naloxone Bystander Intervention Theory and Skills Transfer Theory. The first addresses how harm reduction and low-threshold service contexts create non-judgemental environments that support in-group norms of helping among people who use drugs, strengthening the social identity conditions necessary for peer-to-peer naloxone distribution to succeed. The second addresses how skills training enables confident and effective overdose response. The review also identifies stigma as a significant mechanism that can disrupt these processes and undermine intervention effectiveness.

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Why is it important?

Understanding why naloxone works, not just that it works, is critical for designing and scaling overdose prevention programmes that function in real-world conditions. The realist review approach generates actionable, context-sensitive theory that can guide implementation decisions about training design, distribution models and service environments. The finding that low-threshold harm reduction contexts and social identity processes are active ingredients, not just delivery mechanisms, has direct implications for service commissioning and policy, particularly regarding the peer distribution model that many naloxone programmes rely on. Stigma's role as an active barrier to intervention effectiveness has equally direct policy relevance, particularly in the UK context where drug-related death rates remain among the highest in Europe.