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WASHINGTON — Amid a worsening opioid epidemic, the overdose-reversal drug naloxone has taken center stage. Fire and police departments across the country stock the drug; nonprofits aim to get it into the hands of millions of residents as a bystander intervention.

But a controversial new working paper has raised the question of whether the urgent push to expand naloxone access may be doing more harm than good.


The paper, published online last week, aimed to estimate the changes in behavior resulting from expanded naloxone access. Researchers found that after states passed naloxone access laws, opioid-related emergency room visits and opioid-related theft both rose, and no decrease was observed in opioid-related mortality. Their most troubling results came in the Midwest, where the researchers measured a 14 percent increase in opioid-related mortality attributable to expanded naloxone access.

That, co-authors Jennifer Doleac and Anita Mukherjee said, illustrates that by reducing the likelihood of the worst outcome of opioid use — death — greater access to naloxone reduces disincentives for risky behavior.

At a time when naloxone access is viewed as an unambiguous benefit, the new paper elicited strong reactions.


Specifically, many in life sciences and public health spheres, less accustomed to the publication of working papers that have not yet been peer-reviewed, were troubled by the moral implications of publishing research making such impactful claims.

“We expected some pushback from the public health community,” said Doleac. “We know that economists think differently about some issues than people in other disciplines. But the response has been a lot more hostile than I’d expected.”

The paper, titled “The Moral Hazard of Lifesaving Innovations,” contradicts previous research that has found expansion of naloxone access to have no effect on risky behavior. For instance, a recent National Institutes of Health study of two groups of heroin users found no increase in high-risk behavior resulted from increased naloxone access. And an economics paper from last year found that naloxone access laws typically resulted in a reduction in opioid-related deaths of between 9 and 11 percent.

Examining methodology

“I think what’s important for us to take into account is that this is not science in medical best practice,” said Dr. Leana Wen, Baltimore’s health commissioner, who issued a citywide prescription to any individual wishing to purchase naloxone last year and has been a vocal advocate for addiction response.

“The last thing that we need in the middle of an opioid epidemic is for information to come out that further stigmatizes addiction and can cost lives,” Wen said.“I think we have a duty to a higher burden of proof.”

Though the practice of publishing working papers is common in economics, the authors also plan to submit the paper for peer review.

“We took unusually long to post the working paper because we knew it would be so sensitive and [so that] we knew we got it right,” Doleac said. “Before we posted, we got a lot of feedback from people who are expert in this field. It seems like a lot of people are responding as if Anita and I whipped this up over the weekend. We’ve been working on this for two years.”

Wen also criticized the study for what she characterized as misleading methodology. For instance, authors used opioid-related emergency room visits to gauge population-level addiction trends, which Wen said is flawed partly because such visits could also rise in response to better public health campaigns informing drug users of how to seek treatment. And the study looked at a varied set of laws that Wen said likely had disparate impacts on actual naloxone access — making it difficult to draw sweeping conclusions.

Plus, public health experts said, the need for naloxone has become more pronounced even in the two years the authors worked on the study, as the prevalence of fentanyl has led to more overdoses that are also more difficult to reverse.

“Given the substantial change in the riskiness of the drug supply, I think the overdose death numbers would have been been substantially higher had we not deployed naloxone to the extent we did,” said Chris Jones, the director of the National Mental Health and Substance Use Policy Laboratory.

Drug makers’ influence

The movement to make naloxone more widely available is moving quickly — so much so that the issue has become subject to the same influence-peddling that characterizes most health policy issues in Washington.

Kaleo, the manufacturer of Evzio, a popular injectable form of naloxone, disclosed $260,000 in lobbying on naloxone access in 2017. Adapt, the maker of the nasally administered Narcan, reported spending $300,000.

In an interim report, an opioid crisis commission empaneled by President Trump recommended the health secretary negotiate a reduced naloxone price for government entities — a strategy the Department of Health and Human Services has yet to indicate it will pursue.

In the meantime, manufacturers have worked to maintain their reputation as good actors, particularly after Kaleo drew criticism for hiking the price of a single device to $4,500. The company announced last summer that it had donated 250,000 units of its auto-injector to communities in the last two years.

But the authors of the latest study say that the wider effects of naloxone’s penetration deserve further examination.

“This is something we wrestled with, because neither of us think it would be better if we saved fewer lives,” Doleac said. “I think we tried very hard not to draw that conclusion. But broadening naloxone access as the policies are currently being implemented is not helping and in some places making it worse. To us, the takeaway is not to restrict access to naloxone — it’s that we need to make sure we are doing other things that address the root cause of the crisis.”

  • Nalaxone does save lives and I, for one, don’t think we should be judging the “motives” of people who need these drugs. If my loved one or child was an addict, I want the drug to be available that might save their life should they overdose. Do we deny diabetics medications to reduce their blood sugar when they are having a hyperglycemic crisis because they ate something they shouldn’t have or somehow messed up their insulin dosage or (heaven forbid) they ran out of money and couldn’t afford their medication? No, we don’t. Does the availibility of insulin cause people to deliberately not follow their diet/medication plan. Maybe in very rare cases but you see where I’m going here. Addiction is a very real disease, not a moral failing. It could happen to any of us or a loved one at any time, just like cancer or diabetes. Nobody wants to become an addict.

  • This will no doubt spread like a virus infecting the public discourse on harm reduction and public health, damaging much of the progress we have made in the field. The paper is based on poorly-evidenced assumptions of behaviour patterns, it is written in stigmatizing language, and has methodological limitations that would not hold up to standards of scientific rigour needed to draw these kinds of conclusions about causation.

    In light of the paper’s morally-flawed conclusions making way into public discourse, we must remember that “the possibility of renewal exists so long as life exists.” (Dr. Gabor Maté)

    • In 12 step lingo “renewal” is “spiritual awakening”. You have to get to Step 12 after going through the first 11 steps to get renewal. Most addicts of all types, if they even read the 12 and 12 never get close to renewal because they think that are their own higher power or they think it’s a cult. But they should go to one meeting, since dope dealers hangout in the parking lot and usually can score some NA newbie with a dime bag or more. Trust me, they’re not peddling Narcan.

  • I see that Dr. Wen has taken a page out of our president’s playbook. The statistical rigor in this paper trumps anything that’s come before it; just because you don’t like the finding doesn’t mean it’s misleading or wrong. If you can’t acknowledge the unintended side effects of policies, you’re not doing your job as a policymaker.

  • Is the death rate rising in those stated because opioid usage is increasing? This study apparently took 2 years so would addiction increases been factored in? Not sure this is a slam dunk conclusion

  • What became of the proposal that anyone given Naloxone in a Massachusetts ER be given the choice of entering detox then and there or being adjudicated a danger to self and admitted to psych inpatient for minimum of 72 hours? As someone who cares, I felt that approach made a lot of sense, that we should at least give it a try. I need an update – anyone?

  • Naloxone does not impact a person’s desire to take opioids, but it may help keep them alive long enough to decide to quit. Most people who take opioids do quit as they get older or as they get sicker.

    Also, many people die of an overdose while waiting for treatment to be available to them. Naloxone is part of the response to opioid addiction but not the total solution.

  • Ed, if people are not dopefiends because they expect to be rescued by naloxone, then why are we wasting my taxpayer dollars paying for my EMT squad to buy this stuff? I know, you’re an LADC, so you mustbhave a good idea of the relapse rates.

  • While I am not sure about the study results they are at least worth thinking about. Occasionally I have had one my addicted patients refuse a naloxone prescription because they were concerned that having it would tempt them to use. Anecdotes like that should not be used to determine public health interventions, but they should make us consider unexpected or unwanted effects of such interventions

  • Naloxone is the modern version of Russian Roulette. You have to think like an addict, some of whom have been rescued more than a dozen times with naloxone. They question they all ask themselves: how many times can I overdose and get naloxone rescue before my luck runs out? Sadly for many they wind up with the proverbial six gun with bullets in all the chambers and a one way trip to the morgue.

    • We don’t need sensationalism and superficial analysis at this point in an unprecedented wave of lethality. Urban myth is worthless too. People with OUD injecting drugs are not injecting more drugs because Naloxone Hydrochloride is available. People with OUD are injectioning drugs because it’s the most efficient route of administration and they know that. They are addicted and incapable of abstaining. They face withdrawal multiple times per day. And now they are being preyed upon by ruthless entrepreneurs marketing fentanyl adulterated/substituted heroin because it maximize profit. And our response to this is to conduct a study that concludes a life saving overdose-reversing intervention is making things worse? Shame on you!!!

    • Exactly true
      The addicts know they can be rescued so they risk taking “just one little bit more” only to find out that the drug was either laced or was miscalculated and they are now in trouble “again” and sometimes the Naloxone just isn’t enough to grab the Mu tightly enough to or long enough to hold out for the dose of opioid given
      The issue is do we provide a safety net or let them go on their own? I think we have an obligation to get the reversing agent to as many people and places as we can BUT we need to find better and far more effective methods to treat them rather than just try to save them till the next round
      Dr. Dave

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