OVERDOSES IN THE UNITED STATES: Overdose deaths remain at historically high levels in the United States. The Centers for Disease Control and Prevention (CDC) estimates that over 105,000 people died from overdose in 2023.1 In addition, provisional data from CDC now show that overdose deaths have declined throughout 2024, with a projected decline of nearly 27% in the 12-months ending December 2024 compared to the 12-months ending December 2023.2 Most of these deaths involved opioids. Although illicitly manufactured fentanyl has been a significant driver of deaths, other drugs in the illicit drug supply have become increasingly lethal and unpredictable. For example, overdose deaths involving illicit stimulants such as cocaine and methamphetamine—often in combination with opioids—have also risen.3 In addition, xylazine, an active ingredient in a non-opioid sedative approved by FDA for use in animals, but not approved for use in humans, is increasingly added as an adulterant to the illicit drug supply. Given these realities, it is important that everyone has access to accurate and timely information about overdose risk and prevention—understanding what to look for and how to respond when an overdose occurs can help save lives. Evidence-based interventions are available—knowing when and how to use them can help end the overdose crisis.

TOOLKIT PURPOSES AND AUDIENCES: The primary purpose of this Toolkit is to educate a broad audience on overdose causes, risks, and signs, as well as the steps to take when witnessing and responding to an overdose. It provides clear, accessible information on opioid overdose reversal medications, such as naloxone and nalmefene. This Toolkit serves to complement, not replace, training on overdose prevention and response. It is also intended to augment the use of other overdose prevention tools for community engagement and planning, as well as enhance provider education across multiple practice areas. Overdose education and response tools have the greatest impact when focused on people who use drugs because they are most likely to witness and respond to an overdose.4 However, it is important to recognize that anyone could witness an overdose—whether on the street, at work, at home, in a clinical setting, or in a school. This Toolkit is therefore available for everyone to provide basic knowledge on how to recognize and respond to an overdose. Some audiences may benefit from tailored information, guidance, and resources. Therefore, this Toolkit also includes sections for specific audiences, including people who use drugs (and their family members or caregivers) in Appendix 1; people who use prescription opioids in Appendix 2, practitioners, and health systems in Appendix 3, and first responders in Appendix 4. Appendix 5 of this Toolkit also includes information and links to resources on policy and systems considerations for planning community overdose prevention and response initiatives...