A call for compassionate opioid overdose response

High dose and long-acting opioid overdose reversal drugs can precipitate withdrawal in people who are opioid dependent. Products recently brought to market for community use in the United States (US) have drawn international concern because of their increased risk of withdrawal. At the March 18–19, 2024, Compassionate Overdose Response Summit & Naloxone Dosing Meeting, a panel of harm reduction experts issued the following call to action: 1) people who use drugs should be directly involved in decisions regarding the research, development, selection, and distribution of opioid overdose reversal products; 2) regulatory agencies and pharmaceutical manufacturers should carefully consider and communicate the risk and duration of withdrawal associated with higher dose and longer-acting opioid antagonists; 3) take-home naloxone kits should include at least two doses of an intramuscular (IM) product containing 0.4 mg or an intranasal (IN) product containing ≤4 mg; 4) At this time, high dose and long-acting opioid antagonists have no use in acute opioid overdose response; and, 5) overdose response educational materials, instructions on overdose response, and training should emphasize the restoration of breathing, avoiding withdrawal, and compassionate post-overdose support and care. High dose and long-acting opioid overdose reversal drugs were approved without testing for withdrawal and are often aggressively marketed despite decades of evidence from naloxone distribution programs worldwide that the ideal dose of naloxone is one that restores breathing without inducing withdrawal. Government agencies should direct resources to harm reduction programs to make standard dose take-home naloxone products widely available among people who use drugs. Lay bystanders, people who use drugs, their families, and professional first responders can learn and apply a compassionate approach to opioid overdose response.