PROJECT SUMMARY The United States is experiencing the worst drug overdose epidemic in history. This crisis has been greatly exacerbated by the emergence of potent synthetic opioids, particularly fentanyl and related analogs. Fentanyl is now the most common adulterant in heroin and has been identified in counterfeit prescription pills and illicit drugs such as cocaine. Only a small amount of fentanyl (the equivalent of several grains of salt) can lead to a fatal overdose. Its presence in the illicit drug supply thus poses great risk to those who unknowingly consume the substance. Over 30% of all drug overdose deaths in the US are due to synthetic opioids (mostly fentanyl), yet few strategies aimed at reducing risk of fentanyl overdose have been developed. In this randomized controlled trial, we will test the efficacy of a novel, theory-based fentanyl overdose education and counseling intervention that incorporates “take-home” rapid fentanyl testing strips in reducing rates of overdose. The study will be conducted in Rhode Island, a state with the tenth highest overdose rate in the nation and in which over half of drug-related deaths are due to fentanyl. We will recruit a community-based sample of 500 young adults aged 18 to 35 who use heroin or illicit stimulants, counterfeit prescription pills, or inject drugs. In the intervention arm, individuals will participate in the RAPIDS intervention, a novel fentanyl overdose education and counseling program that provides information about the dangers of fentanyl, motivational interviewing to increase willingness to use rapid fentanyl test strips and engage in harm reduction behaviors, hands-on training on how to use the strips, and opportunities to discuss and role-play how to implement harm reduction behaviors. Individuals randomized to the control arm will receive standard overdose education and naloxone distribution. The primary outcome will be the rate of self-reported overdose observed over the 12-month follow- up period. We will supplement the primary endpoint with data on fatal and non-fatal overdose events ascertained through a CDC-funded statewide overdose surveillance system. The Specific Aims of this study are to: 1) Assess efficacy of the RAPIDS intervention in reducing rates of overdose among young adults who use drugs; 2) Examine the degree to which reductions in rates of overdose are mediated by increases in information, motivation, behavioral skills, and self-efficacy regarding fentanyl, rapid fentanyl testing, and harm reduction practices; and 3) Explore whether there is heterogeneity of treatment effect related to key participant characteristics. Our study is highly significant because it directly addresses crucial knowledge gaps in how to best reduce risk of overdose among young adults in the face of an escalating fentanyl epidemic. The study is highly innovative because it will be the first in the United States to test the efficacy of a novel overdose education and counseling intervention that incorporates take-home rapid testing technology to detect exposure to fentanyl in a population of people who use drugs. In sum, the results of this research will significantly enhance public health efforts to prevent overdose among young adults.

PROJECT NARRATIVE This study will test the efficacy of a novel drug-checking intervention to prevent fatal and non-fatal overdose among young adults who use drugs. We will evaluate whether the incorporation of rapid fentanyl testing into a theory-driven overdose education and counseling program reduces rates of overdose compared to standard overdose education and naloxone distribution. Results from this study will significantly improve public health efforts to address the fentanyl overdose epidemic and reduce harms associated with exposure to drugs contaminated with fentanyl among young adults.