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More Is Not Always Better: Challenging Calls for High-Dose Naloxone

By Stacey Mckenna

Overdose deaths have skyrocketed across the United States in recent years, increasing by 622 percent between 2000 and 2020, with more than 112,000 lives lost in 2023. This crisis has been largely driven by the proliferation of potent synthetic opioids such as illicitly manufactured fentanyl, which is up to 50 times stronger than heroin.

The opioid antagonist, naloxone, is an especially important harm reduction tool in this landscape. Naloxone binds to opioid receptors in the brain, preventing other opioids, such as fentanyl or heroin, from binding to and activating them. The U.S. Food and Drug Administration (FDA) first approved the medication for the reversal of opioid overdoses in 1971. When administered in a timely manner, naloxone can restore breathing within minutes and successfully reverse 75 to 100 percent of overdoses.

Consequently, lawmakers and government agencies across the country have taken steps to improve access to naloxone. State legislatures have passed laws providing immunity to laypeople who administer the medication, authorized statewide standing orders to facilitate prescription-free pharmacy access, and purchased naloxone in bulk for direct distribution and to pass along to community-based organizations and first responders. Last year, the FDA approved intranasal naloxone products for over-the-counter sale for the first time.

However, with novel, increasingly potent synthetic opioids dominating the illicit supply, some medical experts worry that naloxone as we know it is simply not good enough anymore. In fact, in 2021, the FDA approved both higher-dose naloxone products and new, longer-lasting opioid antidotes, and some government agencies have begun purchasing these products for distribution in their communities.

This policy study aims to inform legislators and public health decision-makers about how high-dose naloxone fits into federal, state, and local efforts to combat the opioid overdose crisis. We examine the research on naloxone efficacy—in laboratory and medical settings and in the real world—and assess potential drawbacks associated with alternatives to standard-dose naloxone.

R Street Shorts No. 135 Washington, DC: R Street, 2024. 10p.

Characterizing prescription opioid, heroin, and fentanyl initiation trajectories: A qualitative study

By Tasha Perdue aRobert Carlson bRaminta Daniulaityte cSydney M. Silverstein bRicky N. Bluthenthal dAvelardo Valdez eAlice Cepeda

The purpose of this study is to describe opioid initiation within each of the three waves from the perspective of people who use illicit opioids, with a focus on emerging pathways into fentanyl use. We noted supply-side changes as influencing trajectories in all three waves. However, we also noted differences in the experiences of prescription opioid and heroin initiation, with these trajectories influenced by pharmacological effects, pain management, curiosity, intergenerational use, pricing, and peers. In comparison, most participants were unaware that they were initiating fentanyl, and many reported overdosing with their first use of fentanyl. We identified a trajectory into fentanyl with limited to no prior heroin use among a few participants.

Social Science & Medicine Volume 340. January 2024, 11pg