What is naloxone? Should it be available over the counter?

Naloxone is a medication that can help reduce opioid overdose deaths and save the lives of thousands of people. What are the benefits and should it be available OTC? Learn more here.

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Overdose deaths are preventable!

The most striking statistic about the opioid epidemic is the number of deaths due to overdose, some 25,000 a year. And between 1999 and 2014, there have been a total of 165,000 deaths due to prescription opioid pain medications alone.

Sadly, every single one of these deaths was preventable. I’m not talking about action to limit access to the prescription of opioids or policies to reduce and treat addiction though. I’m referring to access to naloxone, a medication that instantly reverses an overdose from opioids.

Is increased access to naloxone the answer?

There is a push in the public health field and even local, state, and federal government to increase the ease of access to naloxone but, as with everything related to addiction, controversy exists and there’s plenty of pushback despite the incredible effectiveness of naloxone.

But what is naloxone? How does it reverse opioid overdoses? What is the controversy over naloxone and should it be made over the counter? We answer more in this article and invite your questions in the comments section below.

What is naloxone?

Naloxone is an mu opioid receptor (MOPR) antagonist [1].

All opioid drugs (morphine, oxycodone, heroin, methadone, etc.) function by binding to the MOPR. Opioids are agonists at the MOPR because they activate it while naloxone is an antagonist because it blocks or shuts down the activity and function of the MOPR. Naloxone can even kick off short acting opioids like heroin or oxycodone off of the MOPR and stop their functions [2]. This is the most important property of naloxone and is why it is effective at stopping overdose.

Opioids and breathing rate

The mu opioid receptor exists in many places throughout the body and endogenous opioids (opioids that your body makes normally) have many important functions in normal physiology. For example, MOPR in the spinal chord are vital for pain control, while MOPR in the brain are involved in the perception of pain as well as mood and reward. MOPR also exist in the intestine and help to regulate peristalsis (contractions of the intestine).

MOPR present in the brain are also critical in the regulation of breathing rate [3]. In fact, opioid overdose usually occurs due to the slowing of breathing rate to deadly levels. This is known as respiratory depression.

The lungs, like other organs such as the heart, are controlled through nerve signals coming from the brain, specifically the medullary region of the brain stem [3]. MOPR and endogenous opioids are present in this region and the action of exogenous opioids (any opioid drug not produced by the body, such as oxycodone or heroin) significantly inhibits the activity of the neurons in this region, which results in lowering of the breathing rate. In some circumstances, the respiratory depression can be so significant that it’s fatal.

Factors that contribute to opioid overdose

1. Dose.

At what dose an opioid may cause lethal respiratory depression is difficult to estimate because it involves many factors such as:

  • metabolism
  • tolerance
  • whether the opioid has been taken in combination with other drugs

For example, heroin and morphine are metabolized at different rates so if you start on one and then switch to the other, an unexpected physiological effect can occur (such as overdose).

2. Tolerance to opioids.

Tolerance is a significant factor for overdose because different MOPR in different parts of the body respond differently to an exogenous opioid. Tolerance builds up much faster four the rewarding/psychological aspects of opioids than the respiratory effects [2]. This means an addict may take a higher dose in order to satisfy the “high” but can still suffer from a lethal overdose because the tolerance is not as high for the respiratory control function of opioid. Furthermore, overdose often occurs after periods of abstinence when the psychological dependence still exists but the respiratory tolerance was reduced—the abstinent addict takes the same dose as he/she is used to but overdoses because this is most likely not a dose the lungs can tolerate [2]. Sadly, this often happens after release from detox or rehab clinics that stress abstinence only treatment programs.

3. Mixing substances.

Another common cause of overdose is use in combination with other drugs. Both benzodiazepines and alcohol can act to lower breathing rate but if taken in combination with opioids, the respiratory depression that occurs after is much greater than each drug would cause on their own.

How does naloxone reverse opioid overdose?

Regardless of the specific biological reason, the ultimate cause of the overdose is the opioid itself and this is where naloxone comes in. The opioid drug is acting at MOPR in the medulla to inhibit those neurons and suppress the breathing rate but naloxone is able to come in and kick the opioid off the MOPR. This allows breathing rate and other brain functions to return to normal and death from overdose is prevented.

Naloxone and the harm reduction approach

While it’s true that naloxone does not cure an opioid addict of their addiction and it is not a treatment like methadone or buprenorphine, but it is a life saving medication that falls into the category of harm reduction [1]. Harm reduction states that major public health problems (such as the ongoing opioid epidemic) are complex and require short-term solutions to help reduce the damage of the problem until long-term solutions can be developed. Naloxone does not stop the opioid epidemic and will not prevent a heroin addict from seeking out heroin, but it will prevent death due to overdose, accidental or otherwise.

However, the controversy over naloxone and the harm reduction approach is part of the same rhetoric that has persisted around addiction for centuries, namely an addict is thought of as a weak-willed, moral failure and society should do nothing to help him to continue his deviant behavior. If naloxone is made over the counter, some argue, this will just make it easier for addicts to get high by not worrying about the risk of overdose. They claim that naloxone is just a temporary fix and addicts will just overdose again and again (Maine Governor Paul LePage made a similar argument when he decided to veto a bill that would make naloxone over the counter in that state. Thankfully LePage’s veto was successfully overridden and naloxone will soon be available without a prescription in Maine).

However, such arguments completely ignore the overwhelming scientific evidence that addiction is a medical disease of the brain in which drugs hijack behavior. Increased access to naloxone helps to save lives and gives an addict a chance to enter a medication-based treatment program and get their life back on track.

A similar argument is made against another harm reduction approach: education to high school students about safe sex and increased access to condoms. Critics say that teaching kids about condoms will encourage them to have sex. The reality of course is that kids are having sex whether the critics like it or not because the biological drive to do so is intense. By educating these youths on safe sex and making condoms available you are recognizing that you can’t stop the behavior in the short term but availability of condoms at least makes sex safer.

Of course, the harm reduction debate about opioid addiction has been raging for years. One of the first applications of the strategy was in the initiation of needle exchange programs [4]. A well-known fact about intravenous drug use (i.e. “shooting up”) is that sharing needles increases the spread of sexually transmitted diseases like HIV and Hepatitis C. The harm reduction principle states that you can’t stop a heroin addict from shooting up but you can make sure that he or she does not risk the spread of HIV or HepC though use of infected needles. And the result? Needle exchange programs are an unequivocal success [5]. The rates of HIV and HepC after a needle exchange program is begun are drastically lower than before and the results are consistent in every city in which the programs are implemented [6].

Similarly, studies confirm that naloxone provided to heroin addicts also drastically reduces overdose deaths in trial programs [7, 8]. As such, making naloxone over the counter is a common sense and effective harm reduction strategy to help curtail opioid over dose deaths [9]. However, easier access to naloxone is only an effective step if there is also increased access to treatments such as methadone and buprenorphine.

The opioid epidemic… and your questions

This week the opioid epidemic has claimed another high profile life—the iconic rock star Prince died of a Percocet overdose (Percocet contains both acetaminophen and the powerful opioid pain medication oxycodone). And a few years ago the highly acclaimed actor Phillip Seymour Hoffman died of a heroin overdose. If naloxone were immediately available to them, both of these artists would probably still be alive today.

If you have any additional questions or comments regarding the opioid epidemic, naloxone, and whether it should be available over-the-counter, feel free to post them below. We try to provide a personal and prompt answer to all legitimate inquiries or refer you to someone who can help.

Reference Sources: 1. Wermeling DP. Opioid harm reduction strategies: focus on expanded access to intranasal naloxone. Pharmacotherapy. 2010;30(7):627-31.
2. White JM, Irvine RJ. Mechanisms of fatal opioid overdose. Addiction. 1999;94(7):961-72.
3. Pattinson KT. Opioids and the control of respiration. British journal of anaesthesia. 2008;100(6):747-58.
4. Des Jarlais DC, et al. Doing harm reduction better: syringe exchange in the United States. Addiction. 2009;104(9):1441-6.
5. Bastos FI, Strathdee SA. Evaluating effectiveness of syringe exchange programmes: current issues and future prospects. Social science & medicine. 2000;51(12):1771-82.
6. Abdul-Quader AS, et al. Effectiveness of structural-level needle/syringe programs to reduce HCV and HIV infection among people who inject drugs: a systematic review. AIDS and behavior. 2013;17(9):2878-92.
7. Centers for Disease C, Prevention. Community-based opioid overdose prevention programs providing naloxone – United States, 2010. MMWR Morbidity and mortality weekly report. 2012;61(6):101-5.
8. McDonald R, Strang J. Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria. Addiction. 2016.
9. Dowell D, et al. CDC Guideline for Prescribing Opioids for Chronic Pain – United States, 2016. MMWR Recommendations and reports : Morbidity and mortality weekly report Recommendations and reports / Centers for Disease Control. 2016;65(1):1-49.
10. DrugAbuse: Overdose Death Rates
11. CDC: Injury Prevention & Control: Opioid Overdose
12. HuffingtonPost: Dying To Be Free
13. Public News Service: “Pro-Life?” LePage’s Anti-Naloxone Veto
14. Rachel Maddow Show: Maine lawmakers override LePage’s callousness drug policy
About the author
Derek Simon is Postdoctoral Fellow at the Rockefeller University researching the neuroscience of drug addiction using rodent behavioral models. Upon completing his PhD in 2012, Dr. Simon switched from endocrinology to addiction biology and he is currently researching 1) the role of learning and memory in opioid addiction and 2) the interaction between cannabinoids and opioids. He is passionate about increasing public understanding of addiction and is active in science communication and writing. Check out Derek's Addiction Blog and Twitter handle: @derekpsimonphd
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