Why Naloxone Wears Off Before the Opioid Does Opioids depress breathing by binding to opioid receptors in the brainstem. Naloxone displaces them and reverses the respiratory depression, but its duration of action is usually 30–90 minutes, while methadone has a half-life of 15–60 hours. Once the naloxone wears off, the opioid still circulating rebinds and respiratory depression can return. This is why JRCALC advises conveying all opioid overdoses to hospital, even after a good initial response to naloxone, and observing patients who have taken methadone for at least 8 hours. Source: JRCALC Plus, Naloxone hydrochloride, Patient advice/follow up treatment (accessed September 2026). The why underneath the guideline. Always work to current JRCALC and local Trust policy. Learn.Adapt.Respond #studentparamedic #paramedic #naloxone #opioidoverdose #JRCALC