Staff Perspective: Who Can? We Can. Narcan! - A Naloxone Primer in Three Parts
PARTs I & II: Biology and History
As a Suicide Prevention Subject Matter Expert, most of my time these days is spent learning and sharing information to prevent suicide among military-connected individuals. That focus means I’m not always up to date on the evolving landscape of substance use disorders (SUDs), risk management, and treatment.
At one point in time, I provided SUD treatment across levels of care in a range of settings in both DC and Baltimore. It should be noted that that “point in time” started last century and ended 15 years ago. So when I volunteered to write this blog, I initially thought, “I could write this with my eyes closed.” (Ah, the hubris of doctorate-level providers, amirite?) My wake-up call was as swift as it was humbling—the field has changed as much as the neighborhood I grew up in.
After overthinking it, I narrowed the list to three possible topics:
- “Being a Substance Use Disorder Treatment Provider Ain’t for the Faint of Heart” – The Importance of Self-Care for SUD Treatment Providers
- “They Used to Prescribe Narcotic Painkillers Like Pez Dispensers—Now All I Got After Surgery Was Acetaminophen and Lidocaine Patches” – Navigating the Balance Between Pain Management and Reduced Opioid Access
- “Who Can? We Can, Narcan!” – A Naloxone Primer
While all three could be informative, I landed on the third—because it allows me to both learn and teach something. So, without further ado…
Let’s Plug In: Science Lesson: How Opioids Work in the Brain
Receptors, Agonists, and Antagonists
Before we can talk about policies, treatment, or even naloxone, we have to understand the science. Opioids don’t just change behavior — they literally rewire the brain. This first part of the “Who Can? We Can, Narcan!” series breaks down what happens inside the nervous system when opioids enter the body. Whether you’re a clinician, a prevention specialist, or someone supporting military-connected individuals, knowing some basics will lay the foundation for understanding both addiction, the dangers of overdose, and a path to recovery.
Picture your brain as a wall covered in power outlets. These outlets control different functions in the body—they are receptors. They are activated when they get “plugged in”. Below are the “plug” options that determine power flow:
- Agonists: Both sockets have plugs = full power
- Partial Agonists: one socket is plugged in = partial power
- Antagonists: outlet is covered = No power + blocks other plugs
Now, the brain has different types of “outlets” that power all sorts of things. Today, we’re going to focus on one type: μ-(Mu) opioid receptors (MOR). They regulate pain relief, improve mood, and decrease breathing to restore homeostasis after stress or injury. The plugs that provide power to these receptors are called opioid agonists, opioid partial agonists, and opioid antagonists–clever, huh? (Kosten & George, 2002)
Tolerance
Your brain naturally produces endogenous opioid agonists (e.g., endorphins) that plug into MORs. But if the pain is chronic, your body may habituate to the effect over time. When that happens, the opioid agonist is still plugged in, but the power provided is no longer strong enough to alleviate pain or improve mood–this is tolerance (DuPen, Shen, & Ersek, 2007). Tolerance occurs for both endogenous and exogenous opioid agonists (opioids from an external source).
Dependence and Withdrawal
With tolerance comes repeated/increased use; subsequently, the brain adapts, reducing its own endorphin production and increasing other endogenous chemicals to maintain relative balance in affected brain systems. Now, the body relies on opioids just to feel normal, which is considered physical dependence (Kosten & George, 2002).
When the exogenous opioid is removed, the resulting chemical imbalance can lead to agitation and anxiety, severe muscle and bone pain, diarrhea and vomiting, chills and/or sweats, insomnia, not to mention increased breathing, blood pressure, and heart rate. That’s withdrawal, and the lived experience is even worse than the description sounds. While not considered life-threatening in most cases, it is agonizing. People experiencing it have reported “feeling like they were dying” or “wishing they would die.” A person in this position is no longer taking opioids to “feel good,” they are taking them to prevent themselves from feeling wretched (Kosten & George, 2002).
Overdose
Quick reminder, the opioid receptors that manage pain and boost mood also suppress breathing. The pattern of increased frequency/strength of opioid use eventually can lead to too much activation → oxygen deprivation → opioid overdose (Bateman, Saunders, & Levitt, 2023). If oxygen deprivation lasts several minutes, it can cause brain/organ damage, which can be fatal. While increased use to offset tolerance and withdrawal can lead to eventual overdose, an overdose can occur with just one use if the opioid is potent enough. This is especially relevant in today’s fight to prevent opioid overdose deaths. The introduction of such potent opioids, such as fentanyl, into the drug market, sometimes mixed with or disguised as less potent opioids, has skyrocketed overdose rates (Bateman et al., 2023).
The way opioids act on the brain helps explain why they’ve followed us through history — from the battlefield to the bedside. Next, we’ll trace how America’s wars and public policies turned medical innovation into recurring opioid epidemics, setting the stage for the crisis we face today.
PART II: History
Wars and Waves: The Interconnected History of Opioid Use and Wars in the US
In Part I, we explored the neurobiology of opioids and how easily the brain’s reward system can be hijacked. But the opioid epidemic isn’t just a story of molecules — it’s a story of people, policy, and history. Each major U.S. conflict has left behind not only physical and psychological scars but also a trail of opioid dependence. This section of the series follows the timeline of how war, medicine, and public perception intersected to create wave after wave of opioid crises.
It Actually Began with Flowers
Opioid use has been around for a long time…like a really long time. There’s evidence that opium from the poppy flower (an exogenous opioid agonist) was first cultivated in ancient Europe close to 8000 years ago (Salavert et al., 2020). That said, opioids didn't really start showing up in American History until the 1600s. From there, our wars turn everyday use into epidemics.
We’ll start in the 1770s, when the US was fighting its first war —the war for its independence…
Wars
Revolutionary War
During the Revolutionary War (1775-1783), laudanum (a mix of opium and alcohol) gained popularity as a go-to for pain relief by American soldiers (Committee on Prevention, Diagnosis, Treatment, and Management of Substance Use Disorders in the U.S. Armed Forces [CPDTM-SUD], 2013). Laudanum and opium use continued following the war as common household remedies, prescribed especially to women for “nervous complaints” and to infants as sleep aids (Levitt, 2013). In the early 1800s, morphine was discovered and was quickly embraced by the medical community as a “miracle drug” for pain and anxiety (Dormandy, 2012).
Civil War
The Civil War (1861-1865) is, to date, the bloodiest war in American history, so it’s not surprising that morphine and laudanum use surged during this time (Courtwright, 2001). Of note, immediately before the Civil War, the invention of the hypodermic syringe and needle enabled direct injection of morphine, revolutionizing pain control — and unfortunately accelerating opioid dependence (Dormandy, 2012). These advances, in conjunction with the devastating mental and physical injuries of the war, resulted in the nation’s first opioid epidemic; it was during this time that Opioid Use Disorder was coined “the soldier’s disease”(CPDTM-SUD, 2013).
In Germany, shortly thereafter, a chemist at Bayer Pharmaceutical Company developed heroin, deemed a safe, non-addictive alternative to morphine (DEA Museum). This proved to be untrue with dire and enduring consequences; as it turns out, heroin is cheaper, more potent, and more addictive than morphine (Murrin, 2008).
Vietnam War and the “War on Drugs”
The Vietnam War era (1950s-1970s) was the next time opioid use reached epidemic levels, fueled by the intersection of returning soldiers and increased availability of heroin in marginalized neighborhoods (Bergen-Cico, 2015). Although this epidemic was less severe than the one following the Civil War, it led to another type of war, the “War on Drugs,” criminal justice-based policies designed to limit drug supply and use (Farber, 2022). The criminalization of drug use/dependence led to limited access to treatment, an increase in overdose deaths, and spikes in co-occurring infectious disease epidemics such as Hepatitis C and HIV/AIDS through the 1980s into the 1990s (Gostin, 1991).
“The War on Terror” and the Waves of the Current Epidemic
In the mid-1990s, deceptive marketing of prescription opioids (POs) ushered in today’s opioid epidemic (Kolodny, 2015; Van Zee, 2009). This epidemic is unique in that it has been marked by distinct waves and persisted for close to 30 years, making it the longest and deadliest in U.S. history (Jenkins, 2021). The first wave began around 1999, and from 1999 to 2011, the PO overdose death rates nearly quadrupled (Chen, Hedegaard, & Warner, 2014).
It is within this opioid wave that the “War on Terror” Takes place. By 2008, more than 10% of active duty service members were taking opioids either legally or illegally, and between 2000 and 2009, PO overdose deaths among Veterans Health Administration patients nearly doubled (Bohnert et al., 2014; CPDTM-SUD, 2013).
After peaking in 2010, prescriptions for POs declined due to efforts to limit access. Heroin use rebounded in 2010, sparking the 2nd wave in the epidemic with heroin overdose deaths peaking in 2016 (CDC, 2025; Rudd et al., 2016). In 2013, however, a more potent opioid drug hit the illicit drug market, marking the 3rd wave and quickly surpassing all other opioids in terms of potency and mortality: fentanyl (CDC, 2025; Ciccarone, 2017).
Fentanyl (and its analogs) and the 4th Wave
Fentanyl was initially synthesized by pharmaceutical companies in the 1950s for hospital use in surgery and treating severe pain (U.S. Drug Enforcement Administration [DEA], 2020). As such, it is 50 times more potent than heroin and 100 times more potent than morphine (DEA, 2020). In 2013, illicitly manufactured fentanyl and its analogs entered the U.S. drug supply, often passed off as heroin, prescription opioids, and/or benzodiazepines, exposing new, unsuspecting users to the highly potent drug (Schueler & Toner, 2017). In terms of impact, by 2016, Fentanyl surpassed both heroin and prescription drugs as the leading cause of opioid-involved overdose deaths in the U.S. (Ciccarone, 2021; NIDA, 2024).
After a slight decline in Opioid overdose deaths from 2017 to 2018, a new pattern in the epidemic has emerged. Described as the “4th wave,” it is unique as it is not due to the decline in one substance as another increases. It is instead due to polydrug use and overdose deaths, specifically fentanyl with methamphetamine and/or cocaine (Ciccarone, 2021). While COVID-19 did not cause the 4th wave, it did exacerbate its impact, further increasing use and related deaths (Manchikanti et al., 2022).
As of 2023, opioid overdose deaths were nearly ten times as high as it was in 1999 (NIDA, 2024). Today, fentanyl-related substances are thought to be responsible for ~75% of opioid overdose deaths in the US (NIDA, 2024).
History shows that with every war, our understanding of opioids evolves — and so does the toll they take. But the story doesn’t end with despair. In Part III, we’ll meet the new heroes in this fight: the scientists, clinicians, and military health professionals driving lifesaving change through education, innovation, and access to medications like naloxone.
The opinions in CDP Staff Perspective blogs are solely those of the author and do not necessarily reflect the opinion of the Uniformed Services University of the Health Science or the Department of War.
Adria Williams, Ph.D., is a Military Behavioral Health Psychologist at the Center for Deployment Psychology (CDP) with the Uniformed Services University of the Health Sciences. Dr. Williams is a suicide prevention subject matter expert and trainer.
Part I & II References
Bateman, J. T., Saunders, S. E., & Levitt, E. S. (2023). Understanding and countering opioid-induced respiratory depression. British Journal of Pharmacology, 180(7), 813–828. https://doi.org/10.1111/bph.15580
Bergen-Cico, D. K. (2015). War and Drugs: The Role of Military Conflict in the Development of Substance Abuse. United Kingdom: Taylor & Francis. https://doi.org/10.4324/9781315631226
Bohnert, A. S., Ilgen, M. A., Trafton, J. A., Kerns, R. D., Eisenberg, A., Ganoczy, D., & Blow, F. C. (2014). Trends and regional variation in opioid overdose mortality among Veterans Health Administration patients, fiscal year 2001 to 2009. The Clinical journal of pain, 30(7), 605–612. https://doi.org/10.1097/AJP.0000000000000011
Centers for Disease Control and Prevention. (2025, June 9). Understanding the opioid overdose epidemic. https://www.cdc.gov/overdose-prevention/about/understanding-the-opioid-overdose-epidemic.html
Chen LH, Hedegaard H, Warner M. ( 2014). Drug-Poisoning Deaths Involving Opioid Analgesics: United States, 1999–2011. NCHS Data Brief No. 166. Hyattsville, MD: Natl. Cent. Health Stat. [Google Scholar]
Ciccarone, D. (2017). Fentanyl in the U.S. heroin supply: A rapidly changing risk environment. International Journal of Drug Policy, 46, 107–111. https://doi.org/10.1016/j.drugpo.2017.06.010
Ciccarone D. (2021). The rise of illicit fentanyls, stimulants and the fourth wave of the opioid overdose crisis. Current Opinion in Psychiatry, 34(4):344-350. https://doi.org/10.1097/YCO.0000000000000717
Committee on Prevention, Diagnosis, Treatment, and Management of Substance Use Disorders in the U.S. Armed Forces, Board on the Health of Select Populations, Institute of Medicine, O’Brien, C. P., Oster, M., & Morden, E. (Eds.). (2013, February 21). Substance use disorders in the U.S. armed forces. National Academies Press. https://doi.org/10.17226/13441
Courtwright D. T. (2001). Dark paradise: A history of opiate addiction in America. Cambridge, MA: Harvard University Press. https://www.hup.harvard.edu/books/9780674005853
DEA Museum. (n.d.). Heroin bottle: Bayer & Co. Retrieved from https://museum.dea.gov/museum-collection/collection-spotlight/artifact/heroin-bottle
Dormandy, T. (2012). Opium: Reality’s Dark Dream. Yale University Press. https://yalebooks.yale.edu/book/9780300175325/opium/
DuPen, A., Shen, D., & Ersek, M. (2007). Mechanisms of opioid-induced tolerance and hyperalgesia. Pain Management Nursing, 8(3), 113–121. https://doi.org/10.1016/j.pmn.2007.02.004
Farber, D. ed. (2022). The War on Drugs: A History. NYU Press Scholarship Online. https://doi.org/10.18574/nyu/9781479811359.001.0001
Gostin, L. O. (1991). The interconnected epidemics of drug dependency and AIDS. Harvard Civil Rights–Civil Liberties Law Review, 26, 114–184. https://scholarship.law.georgetown.edu/facpub/761
Kolodny, A., Courtwright, D. T., Hwang, C. S., Kreiner, P., Eadie, J. L., Clark, T. W., & Alexander, G. C. (2015). The prescription opioid and heroin crisis: A public health approach to an epidemic of addiction. Annual Review of Public Health, 36, 559–574. https://doi.org/10.1146/annurev-publhealth-031914-122957
Jenkins, R. A. (2021). The fourth wave of the US opioid epidemic and its implications for the rural US: A federal perspective. Preventive Medicine, 152, 106541. https://doi.org/10.1016/j.ypmed.2021.106541
Kosten, T. R., & George, T. P. (2002). The neurobiology of opioid dependence: implications for treatment. Science & Practice Perspectives, 1(1), 13–20. https://doi.org/10.1151/spp021113
Levitt, R. (2013). Unsafe Medicine: Laudanum in the 19th Century. Wellcome History, (51), 24-25. https://kclpure.kcl.ac.uk/ws/portalfiles/portal/14660527/Pages_from_Levitt_Wellcome_History_Feb_2013.pdf
Manchikanti, L., Singh, V. M., Staats, P. S., Trescot, A. M., Prunskis, J., Knezevic, N. N., Soin, A., Kaye, A. D., Atluri, S., Boswell, M. V., Abd-Elsayed, A., & Hirsch, J. A. (2022). Fourth Wave of Opioid (Illicit Drug) Overdose Deaths and Diminishing Access to Prescription Opioids and Interventional Techniques: Cause and Effect. Pain Physician, 25(2), 97–124. https://pubmed.ncbi.nlm.nih.gov/35322965/
Murrin, L. C. (2008). Heroin. In S. J. Enna & D. B. Bylund (Eds.), xPharm: The comprehensive pharmacology reference (pp. 1–9). Elsevier. https://doi.org/10.1016/B978-008055232-3.63891-7
National Institute on Drug Abuse (NIDA). (2024). Overdose death rates. https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates
Rudd, R. A., Seth, P., David, F., & Scholl, L. (2016). Increases in Drug and Opioid-Involved Overdose Deaths - United States, 2010-2015. MMWR. Morbidity and mortality weekly report, 65(50-51), 1445–1452. https://doi.org/10.15585/mmwr.mm655051e1
Salavert, A., Zazzo, A., Martin, L., Antolín, F., Gauthier, C., Thil, F., Tombret, O., Bouby, L., Manen, C., Mineo, M., Piqué, R., Rottoli, M., Rovira, N., Toulemonde, F., & Vostrovská, I. (2020). Direct dating reveals the early history of opium poppy in western Europe. Scientific Reports, 10(1), 1-10. https://doi.org/10.1038/s41598-020-76924-3
Schueler, H. E., & Toner, B. B. (2017). Emerging synthetic fentanyl analogs: A review. International Journal of Drug Policy, 46, 150-157 https://doi.org/10.23907/2017.004
U.S. Drug Enforcement Administration. (2020, June). Drug fact sheet: Fentanyl [PDF]. https://www.dea.gov/sites/default/files/2020-06/Fentanyl-2020_0.pdf
Van Zee, A. (2009). The promotion and marketing of OxyContin: Commercial triumph, public health tragedy. American Journal of Public Health, 99(2), 221–227. https://doi.org/10.2105/AJPH.2007.131714
PARTs I & II: Biology and History
As a Suicide Prevention Subject Matter Expert, most of my time these days is spent learning and sharing information to prevent suicide among military-connected individuals. That focus means I’m not always up to date on the evolving landscape of substance use disorders (SUDs), risk management, and treatment.
At one point in time, I provided SUD treatment across levels of care in a range of settings in both DC and Baltimore. It should be noted that that “point in time” started last century and ended 15 years ago. So when I volunteered to write this blog, I initially thought, “I could write this with my eyes closed.” (Ah, the hubris of doctorate-level providers, amirite?) My wake-up call was as swift as it was humbling—the field has changed as much as the neighborhood I grew up in.
After overthinking it, I narrowed the list to three possible topics:
- “Being a Substance Use Disorder Treatment Provider Ain’t for the Faint of Heart” – The Importance of Self-Care for SUD Treatment Providers
- “They Used to Prescribe Narcotic Painkillers Like Pez Dispensers—Now All I Got After Surgery Was Acetaminophen and Lidocaine Patches” – Navigating the Balance Between Pain Management and Reduced Opioid Access
- “Who Can? We Can, Narcan!” – A Naloxone Primer
While all three could be informative, I landed on the third—because it allows me to both learn and teach something. So, without further ado…
Let’s Plug In: Science Lesson: How Opioids Work in the Brain
Receptors, Agonists, and Antagonists
Before we can talk about policies, treatment, or even naloxone, we have to understand the science. Opioids don’t just change behavior — they literally rewire the brain. This first part of the “Who Can? We Can, Narcan!” series breaks down what happens inside the nervous system when opioids enter the body. Whether you’re a clinician, a prevention specialist, or someone supporting military-connected individuals, knowing some basics will lay the foundation for understanding both addiction, the dangers of overdose, and a path to recovery.
Picture your brain as a wall covered in power outlets. These outlets control different functions in the body—they are receptors. They are activated when they get “plugged in”. Below are the “plug” options that determine power flow:
- Agonists: Both sockets have plugs = full power
- Partial Agonists: one socket is plugged in = partial power
- Antagonists: outlet is covered = No power + blocks other plugs
Now, the brain has different types of “outlets” that power all sorts of things. Today, we’re going to focus on one type: μ-(Mu) opioid receptors (MOR). They regulate pain relief, improve mood, and decrease breathing to restore homeostasis after stress or injury. The plugs that provide power to these receptors are called opioid agonists, opioid partial agonists, and opioid antagonists–clever, huh? (Kosten & George, 2002)
Tolerance
Your brain naturally produces endogenous opioid agonists (e.g., endorphins) that plug into MORs. But if the pain is chronic, your body may habituate to the effect over time. When that happens, the opioid agonist is still plugged in, but the power provided is no longer strong enough to alleviate pain or improve mood–this is tolerance (DuPen, Shen, & Ersek, 2007). Tolerance occurs for both endogenous and exogenous opioid agonists (opioids from an external source).
Dependence and Withdrawal
With tolerance comes repeated/increased use; subsequently, the brain adapts, reducing its own endorphin production and increasing other endogenous chemicals to maintain relative balance in affected brain systems. Now, the body relies on opioids just to feel normal, which is considered physical dependence (Kosten & George, 2002).
When the exogenous opioid is removed, the resulting chemical imbalance can lead to agitation and anxiety, severe muscle and bone pain, diarrhea and vomiting, chills and/or sweats, insomnia, not to mention increased breathing, blood pressure, and heart rate. That’s withdrawal, and the lived experience is even worse than the description sounds. While not considered life-threatening in most cases, it is agonizing. People experiencing it have reported “feeling like they were dying” or “wishing they would die.” A person in this position is no longer taking opioids to “feel good,” they are taking them to prevent themselves from feeling wretched (Kosten & George, 2002).
Overdose
Quick reminder, the opioid receptors that manage pain and boost mood also suppress breathing. The pattern of increased frequency/strength of opioid use eventually can lead to too much activation → oxygen deprivation → opioid overdose (Bateman, Saunders, & Levitt, 2023). If oxygen deprivation lasts several minutes, it can cause brain/organ damage, which can be fatal. While increased use to offset tolerance and withdrawal can lead to eventual overdose, an overdose can occur with just one use if the opioid is potent enough. This is especially relevant in today’s fight to prevent opioid overdose deaths. The introduction of such potent opioids, such as fentanyl, into the drug market, sometimes mixed with or disguised as less potent opioids, has skyrocketed overdose rates (Bateman et al., 2023).
The way opioids act on the brain helps explain why they’ve followed us through history — from the battlefield to the bedside. Next, we’ll trace how America’s wars and public policies turned medical innovation into recurring opioid epidemics, setting the stage for the crisis we face today.
PART II: History
Wars and Waves: The Interconnected History of Opioid Use and Wars in the US
In Part I, we explored the neurobiology of opioids and how easily the brain’s reward system can be hijacked. But the opioid epidemic isn’t just a story of molecules — it’s a story of people, policy, and history. Each major U.S. conflict has left behind not only physical and psychological scars but also a trail of opioid dependence. This section of the series follows the timeline of how war, medicine, and public perception intersected to create wave after wave of opioid crises.
It Actually Began with Flowers
Opioid use has been around for a long time…like a really long time. There’s evidence that opium from the poppy flower (an exogenous opioid agonist) was first cultivated in ancient Europe close to 8000 years ago (Salavert et al., 2020). That said, opioids didn't really start showing up in American History until the 1600s. From there, our wars turn everyday use into epidemics.
We’ll start in the 1770s, when the US was fighting its first war —the war for its independence…
Wars
Revolutionary War
During the Revolutionary War (1775-1783), laudanum (a mix of opium and alcohol) gained popularity as a go-to for pain relief by American soldiers (Committee on Prevention, Diagnosis, Treatment, and Management of Substance Use Disorders in the U.S. Armed Forces [CPDTM-SUD], 2013). Laudanum and opium use continued following the war as common household remedies, prescribed especially to women for “nervous complaints” and to infants as sleep aids (Levitt, 2013). In the early 1800s, morphine was discovered and was quickly embraced by the medical community as a “miracle drug” for pain and anxiety (Dormandy, 2012).
Civil War
The Civil War (1861-1865) is, to date, the bloodiest war in American history, so it’s not surprising that morphine and laudanum use surged during this time (Courtwright, 2001). Of note, immediately before the Civil War, the invention of the hypodermic syringe and needle enabled direct injection of morphine, revolutionizing pain control — and unfortunately accelerating opioid dependence (Dormandy, 2012). These advances, in conjunction with the devastating mental and physical injuries of the war, resulted in the nation’s first opioid epidemic; it was during this time that Opioid Use Disorder was coined “the soldier’s disease”(CPDTM-SUD, 2013).
In Germany, shortly thereafter, a chemist at Bayer Pharmaceutical Company developed heroin, deemed a safe, non-addictive alternative to morphine (DEA Museum). This proved to be untrue with dire and enduring consequences; as it turns out, heroin is cheaper, more potent, and more addictive than morphine (Murrin, 2008).
Vietnam War and the “War on Drugs”
The Vietnam War era (1950s-1970s) was the next time opioid use reached epidemic levels, fueled by the intersection of returning soldiers and increased availability of heroin in marginalized neighborhoods (Bergen-Cico, 2015). Although this epidemic was less severe than the one following the Civil War, it led to another type of war, the “War on Drugs,” criminal justice-based policies designed to limit drug supply and use (Farber, 2022). The criminalization of drug use/dependence led to limited access to treatment, an increase in overdose deaths, and spikes in co-occurring infectious disease epidemics such as Hepatitis C and HIV/AIDS through the 1980s into the 1990s (Gostin, 1991).
“The War on Terror” and the Waves of the Current Epidemic
In the mid-1990s, deceptive marketing of prescription opioids (POs) ushered in today’s opioid epidemic (Kolodny, 2015; Van Zee, 2009). This epidemic is unique in that it has been marked by distinct waves and persisted for close to 30 years, making it the longest and deadliest in U.S. history (Jenkins, 2021). The first wave began around 1999, and from 1999 to 2011, the PO overdose death rates nearly quadrupled (Chen, Hedegaard, & Warner, 2014).
It is within this opioid wave that the “War on Terror” Takes place. By 2008, more than 10% of active duty service members were taking opioids either legally or illegally, and between 2000 and 2009, PO overdose deaths among Veterans Health Administration patients nearly doubled (Bohnert et al., 2014; CPDTM-SUD, 2013).
After peaking in 2010, prescriptions for POs declined due to efforts to limit access. Heroin use rebounded in 2010, sparking the 2nd wave in the epidemic with heroin overdose deaths peaking in 2016 (CDC, 2025; Rudd et al., 2016). In 2013, however, a more potent opioid drug hit the illicit drug market, marking the 3rd wave and quickly surpassing all other opioids in terms of potency and mortality: fentanyl (CDC, 2025; Ciccarone, 2017).
Fentanyl (and its analogs) and the 4th Wave
Fentanyl was initially synthesized by pharmaceutical companies in the 1950s for hospital use in surgery and treating severe pain (U.S. Drug Enforcement Administration [DEA], 2020). As such, it is 50 times more potent than heroin and 100 times more potent than morphine (DEA, 2020). In 2013, illicitly manufactured fentanyl and its analogs entered the U.S. drug supply, often passed off as heroin, prescription opioids, and/or benzodiazepines, exposing new, unsuspecting users to the highly potent drug (Schueler & Toner, 2017). In terms of impact, by 2016, Fentanyl surpassed both heroin and prescription drugs as the leading cause of opioid-involved overdose deaths in the U.S. (Ciccarone, 2021; NIDA, 2024).
After a slight decline in Opioid overdose deaths from 2017 to 2018, a new pattern in the epidemic has emerged. Described as the “4th wave,” it is unique as it is not due to the decline in one substance as another increases. It is instead due to polydrug use and overdose deaths, specifically fentanyl with methamphetamine and/or cocaine (Ciccarone, 2021). While COVID-19 did not cause the 4th wave, it did exacerbate its impact, further increasing use and related deaths (Manchikanti et al., 2022).
As of 2023, opioid overdose deaths were nearly ten times as high as it was in 1999 (NIDA, 2024). Today, fentanyl-related substances are thought to be responsible for ~75% of opioid overdose deaths in the US (NIDA, 2024).
History shows that with every war, our understanding of opioids evolves — and so does the toll they take. But the story doesn’t end with despair. In Part III, we’ll meet the new heroes in this fight: the scientists, clinicians, and military health professionals driving lifesaving change through education, innovation, and access to medications like naloxone.
The opinions in CDP Staff Perspective blogs are solely those of the author and do not necessarily reflect the opinion of the Uniformed Services University of the Health Science or the Department of War.
Adria Williams, Ph.D., is a Military Behavioral Health Psychologist at the Center for Deployment Psychology (CDP) with the Uniformed Services University of the Health Sciences. Dr. Williams is a suicide prevention subject matter expert and trainer.
Part I & II References
Bateman, J. T., Saunders, S. E., & Levitt, E. S. (2023). Understanding and countering opioid-induced respiratory depression. British Journal of Pharmacology, 180(7), 813–828. https://doi.org/10.1111/bph.15580
Bergen-Cico, D. K. (2015). War and Drugs: The Role of Military Conflict in the Development of Substance Abuse. United Kingdom: Taylor & Francis. https://doi.org/10.4324/9781315631226
Bohnert, A. S., Ilgen, M. A., Trafton, J. A., Kerns, R. D., Eisenberg, A., Ganoczy, D., & Blow, F. C. (2014). Trends and regional variation in opioid overdose mortality among Veterans Health Administration patients, fiscal year 2001 to 2009. The Clinical journal of pain, 30(7), 605–612. https://doi.org/10.1097/AJP.0000000000000011
Centers for Disease Control and Prevention. (2025, June 9). Understanding the opioid overdose epidemic. https://www.cdc.gov/overdose-prevention/about/understanding-the-opioid-overdose-epidemic.html
Chen LH, Hedegaard H, Warner M. ( 2014). Drug-Poisoning Deaths Involving Opioid Analgesics: United States, 1999–2011. NCHS Data Brief No. 166. Hyattsville, MD: Natl. Cent. Health Stat. [Google Scholar]
Ciccarone, D. (2017). Fentanyl in the U.S. heroin supply: A rapidly changing risk environment. International Journal of Drug Policy, 46, 107–111. https://doi.org/10.1016/j.drugpo.2017.06.010
Ciccarone D. (2021). The rise of illicit fentanyls, stimulants and the fourth wave of the opioid overdose crisis. Current Opinion in Psychiatry, 34(4):344-350. https://doi.org/10.1097/YCO.0000000000000717
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