On March 29, the FDA approved the first ever naloxone product (Narcan) for over-the-counter (OTC), non-prescription use, citing a goal of increasing access and availability of naloxone as part of their commitment to responding to our ongoing overdose crisis.
Naloxone is an opioid overdose reversal agent, and is a true antidote for opioid drugs like fentanyl, which are the primary drivers of our overdose crisis that killed more than 70,000 Americans in 2021. Naloxone works on every known opioid and could theoretically treat every single opioid overdose (and prevent every single opioid overdose death) if available and given in time.
Not only is the move to OTC supported by safety and efficacy data, this is an objectively good move because every opioid overdose death could be prevented by naloxone, and something that many other countries have already done. Many efforts have been made in recent years to expand access to naloxone in the U.S., however, a large body of evidence suggests that significant barriers remain.
While physical and geographical availability and cost are all factors affecting access -- and cost will remain a very real concern with the OTC version -- most of the remaining factors that prevent wider availability and use are related to misinformation and stigma.
Naloxone has been FDA-approved to reverse opioid overdoses in the U.S. since 1971. It works by binding to opioid receptors in the brain and displacing other opioids that cause things like respiratory depression, overdose, and death. It is one of the truest antidotes to exist, and it is effective for every opioid -- even reversing something as potent as carfentanil (Wildnil) at the same, standard dosing.
The only real adverse effect from naloxone is that it can cause opioid withdrawal, which is expected given its intended effect of antagonizing mu opioid receptors. It does not work for other substances (like benzodiazepines and xylazine) and cannot treat conditions like hypoxia, hypercarbia, and acidosis that can occur after opioid overdose, but this does not mean that it does not work. It is important to know that there are no "naloxone-resistant" opioids.
I've heard opposition to naloxone accompanied by the statement, "naloxone does not treat addiction." But it is not intended to, and pharmacologically this would never make sense. This is like saying that life jackets do not prevent boating accidents. This is one of the most frequently-repeated arguments against naloxone even though it is a false premise and a straw-man argument. Naloxone alone will not solve our overdose crisis. Naloxone only treats overdoses, and only works if given in time. Even naloxone itself has more benefits when broader addiction and harm reduction resources are available.
Some people take this myth even further and state that naloxone actually increases overdoses and death rates, often claiming that people who use drugs will use more drugs or more potent drugs if they know naloxone is available. Not only does this not make any sense since naloxone blocks opioid effects and causes miserable withdrawal symptoms in people who use opioids, this idea has been extensively disproven.
However, the belief in naloxone as a "moral hazard" persists. A lifesaving antidote cannot increase overdose deaths; that is a pure fallacy. This myth has been propped up by one single, non-peer reviewed economics study that was widely publicized several years ago despite serious methodological concerns, and in contradiction to all other (and objectively better) evidence; yet, when the paper was eventually published without those conclusions after the peer review process it did not receive nearly as much attention.
What naloxone does do is enable people to survive an overdose so that they might enter recovery. People cannot recover if they are dead. Estimates suggest that for fewer than every six naloxone kits distributed to the community, an overdose is reversed and a human life is potentially saved, which has further societal benefits including significant community financial benefits.
Another major misconception is that naloxone should be restricted because people may not know how to use it if they are not trained or do not have immediate access to medical care or health facilities. Just recently, the Idaho legislature passed a bill limiting who can receive Narcan kits based on this presumption, despite evidence from state health officials that 94% of overdoses reversed in Idaho were performed by people other than first responders and despite concerns that this could quadruple the overdose death rate in the state. In reality, the intranasal naloxone delivery system that OTC Narcan uses was designed intentionally -- using public taxpayer funding no less -- so that it could be used by anyone, even an untrained child, and greater than 90% of the general population can successfully administer it without any training.
In my own work to educate about and distribute naloxone, it often seems like arguments against this lifesaving medicine are never ending. I hear things like naloxone might not last as long as the overdose drug, which is just not borne out in reality. They harp on the fact that there is a risk of pulmonary edema after reversing an overdose, although it is infinitesimally small and William Osler described it in opioid overdose a century before naloxone existed, making an association to naloxone questionable. People will even say that naloxone is a risk to administer because someone may wake up and be aggressive or violent, which is also not true and would only be situational rather than an effect of the drug.
At the end of the day, these arguments can be boiled down to whether a rare, or even imaginary, risk is worse than death because the alternative to naloxone for an unresponsive, apneic overdose patient outside of immediate medical settings is death. And every one of our deaths could be prevented by availability of timely naloxone administration.
To save lives and fight stigma, everyone should have and carry naloxone. You just might save a life. And there is no worse feeling than knowing a life was lost just because naloxone wasn't around.
Ryan Marino, MD, is a medical toxicologist, addiction medicine specialist, emergency physician, and assistant professor at Case Western Reserve University School of Medicine.