Editor’s Note: Dr. Jerome Adams, who served as the US Surgeon General in the first Trump administration, is a well-known professor of pharmacy practice and public health at Purdue University.
One big, beautiful bill law recently passed predicted by experts will cut Medicaid compensation for millions of Americans and, coupled with the proposed abolition of $56 million grants for overdose reversal training and distribution, threaten to undermine progress in reducing mortality from opioid overdose. Medicaid supports the treatment of approximately 1 million people with opioid use disorders, particularly through its expansion.
If federal funds collapse, many people could lose access to care, reversing the hard-earned profits against overdose deaths driven by expanded health care and life-saving tools. As synthetic opioids like fentanyl fuel the ongoing overdose crisis, maintaining progress requires both robust policies and progress in overdose reversal strategies.
Federal estimates show that drug overdose deaths fell sharply to five-year lows in 2024, but last year there still had more than 80,000 deaths. Synthetic opioids were involved in more than half of these cases.
Highly synthetic opioids like fentanyl (HPSOS) that are 50-100 times more potent than heroin, have formed an overdose landscape. Fentanyl can cause rapid respiratory arrest within minutes and often last longer than standard inverters. First responders frequently report that multiple doses of naloxone (best known under the brand name Narcan) must be administered to reverse fentanyl overdose.
Recent analysis by Dr. Mark Gold, The University of Washington’s School of Psychiatry and colleagues explore the challenges of reverse HPSO overdose and utilizing observational studies, lab data and clinical experience. They emphasize that effective reversal requires the agent to be tailored to the efficacy and duration of the opioid. This is a complicated task given the increasingly unpredictable nature of today’s illicit drugs.
Among the options, nasalmefene has emerged as a prominent tool due to its rapid onset and longer duration compared to the standard inverting drug naloxone. It is administered via a simple spray and acts quickly to restore breathing, helping to reduce the risk of “re-drilling”.
However, the American School of Medical Toxicology and the American Academy of Clinical Toxicology are paying attention to the adoption of nalmefene as a primary drug, citing potential risks such as revival of respiratory depression due to prolonged withdrawal symptoms and the weakened effectiveness of the drug.
However, these concerns are not specific to nalmefene, as all opioid antagonists carry similar risks. Furthermore, these risks are easily managed with proper medical surveillance and surveillance. This is the standard practice after inversion.
To put it plainly, we would rather risk having to treat such side effects to living people who have revived, than thinking “if any” about tens of thousands of people each year who are sadly not saved by our current efforts.
The development of new reversal agents such as nalmefene highlights the important need for sustainable research funding to address the evolving opioid crisis. However, recent budget proposals include significant cuts from the National Institutes of Health and the Centers for Disease Control and Prevention, with NIH down to $27.5 billion to a 40% reduction and CDC down to 44% in 2026, threatening research into new treatments and public health responses.
These cuts could halt the progression of innovative solutions such as Compound 368. This increases the potency of naloxone by 7.6 times, resulting in a 10-fold effect, allowing covalent naloxone nanoparticles (CNLX-NPs) to maintain treatment levels for 48 hours to prevent linercutting. While promising, slowing the onset of CNLX-NPs requires pairing with fast acting naloxone for rapid effects. Such potentially life-saving advances rely on consistent funding to move from labs to real-world use.
Policy continues to play an important role in stopping the tide. The World Health Organization recommends limiting access to precursor chemicals used in fentanyl production and increasing international control of their analogs. It’s nice to see this is one of the few areas that the Trump administration agrees with whom. Strengthening border security and surveillance could further limit the supply of illegal HPSOs.
Equally important, HPSOS rapidly induces hypoxia, and therefore receives latest training for first responders and bystanders, highlighting the interaction between reversible agents and immediate CPR. Public awareness campaigns should highlight the efficacy of HPSOS and the need for rapid intervention, new agents such as nalmefene and multiple doses and Narcan, and post-inversion monitoring.
Thankfully, the CDC has reported a recent decline in national overdose deaths. However, vulnerability persists, especially in communities facing geographical, racial, or demographic disparities.
The rise in stimulants added to fentanyl, which promoted a 50-fold increase in related overdose deaths between 2010 and 2021 and accounted for 32.3% of fatal overdose, complicating the crisis. These contaminated drugs turn non-opioid use into a fatal risk. This is because users often lack opioid resistance. A comprehensive strategy combining policy, education and innovative reversal tools is essential to addressing this diversity threat.
Protection of Medicaid and overdose prevention funds is important to maintain progress in the fight against deaths caused by opioid overdose. Combining these efforts with evidence-based training and advances in reversal strategies will allow us to better equip our communities to confront the evolving opioid crisis and save lives.
