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Transl Psychiatry

The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies

1 National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, 100191 Beijing, China

2 Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 100191 Beijing, China

Yongbo Zheng

Muhammad zahid khan.

3 Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, 100871 Beijing, China

Fentanyl is a powerful opioid anesthetic and analgesic, the use of which has caused an increasing public health threat in the United States and elsewhere. Fentanyl was initially approved and used for the treatment of moderate to severe pain, especially cancer pain. However, recent years have seen a growing concern that fentanyl and its analogs are widely synthesized in laboratories and adulterated with illicit supplies of heroin, cocaine, methamphetamine, and counterfeit pills, contributing to the exponential growth in the number of drug-related overdose deaths. This review summarizes the recent epidemic and evolution of illicit fentanyl use, its pharmacological mechanisms and side effects, and the potential clinical management and prevention of fentanyl-related overdoses. Because social, economic, and health problems that are related to the use of fentanyl and its analogs are growing, there is an urgent need to implement large-scale safe and effective harm reduction strategies to prevent fentanyl-related overdoses.

Introduction

Fentanyl was first developed in 1960 by Paul Janssen as a potent opioid anesthetic and analgesic. At the time, fentanyl was the fastest-acting opioid discovered to date and more powerful than morphine (50–100 times) and heroin (30–50 times) 1 , 2 . Transdermal, intravenous, and transbuccal fentanyl administration and several other drugs with chemical structures that are similar to fentanyl have been developed, approved, and used for surgical anesthesia and the management of severe cancer pain and perioperative pain, eventually becoming the most often used synthetic opioid in clinical practice 3 – 5 . Since 1979, fentanyl and its analogs have been synthesized in laboratories and sold as heroin substitutes or mixed with other illicitly sourced drugs, leading to an increase in fentanyl-related overdose deaths 6 , 7 . Postmortem studies have consistently found pulmonary edema, congestion, and needle puncture sites in these victims. Based on data from the National Vital Statistics System, 599,255 drug overdose deaths occurred from 1979 to 2016 in the United States, and the overall mortality rate has seen exponential growth. Fentanyl-related overdose deaths predominantly occurred in the northeastern United States, mostly affecting younger people (20–40 years of age), and grew sharply since 2013 8 .

Rapid death from ingesting fentanyl has become increasingly more common. Its high potency, fast onset of action, and duration of the desired effect may be particularly important contributing factors to the higher risk of overdose deaths and social consequences 9 . Fentanyl has become a major contributor to cocaine-related fatal overdoses. The rate of fentanyl-related overdose deaths increased 55% between 2015 and 2017 in New York city 10 , 11 . Synthetic opioids are also increasingly detected in illicit supplies of heroin, methamphetamine, and counterfeit pills. Analysis of a sampling of 1 million unique patients’ urine drug test (UDT) specimens showed that positivity rates for fentanyl have increased by 1850% among cocaine positive UDT results and increased by 798% among methamphetamine-positive UDT results between January 2013 and September 2018 12 . This mixture may lead to the increases in cocaine-related and methamphetamine-related overdoses. Moreover, the number of fatal overdoses from synthetic opioids, primarily fentanyl and its analogs, was 19,547 in 2016 in the United States, and this rate increased by 88% per year from 2013 to 2016 13 – 16 . The incidence of heroin-related overdose deaths stabilized in 2017, whereas deaths that involved other synthetic opioids continued to increase 17 . Given the substantial individual and public health threats of this emerging problem, the present review summarizes the epidemic and evolution of illicit fentanyl use, its pharmacological mechanism of action, its adverse consequences, and the clinical management and prevention of fentanyl-related overdoses.

Epidemic and evolution of illicit fentanyl use

Fentanyl is currently approved and commonly used to treat breakthrough pain in cancer patients and various other clinical conditions that involve noncancer pain, such as postoperative pain. However, its potential for abuse and the rise in overdose deaths pose a serious challenge to public health 18 – 21 . Deaths that were attributable to illicit fentanyl use were first reported in the early 1980s and occurred sporadically in the United States 6 , 7 , 22 . A surge in the occurrence of fentanyl-related fatalities among illicit drug users occurred in 2006. A total of 1013 deaths in six states occurred from April 4, 2005, to March 28, 2007 23 . Since then, the prevalence of opioid-related mortality has increased persistently, and the number of reported fentanyl-related deaths more than doubled (from 2628 to 5544) between 2012 and 2014 21 , 24 , 25 . The rate of fentanyl-related overdose deaths increased from <15% in 2010 to ~50% in 2017 in Marion County, Indiana 26 . Overall overdose deaths and first-responder calls increased in a community-based sample in an impoverished neighborhood in Vancouver, Canada, in 2017, and fentanyl was detected in 52% of the subjects who were prescribed opioid agonist therapy 27 . At the same time, fentanyl-related deaths also increased in Australia 28 , 29 .

The presence of fentanyl and its analogs has become a central contributor to the increase in the number of opioid-related overdose deaths. Preliminary estimates of opioid overdose deaths in the United States in 2016 revealed that fentanyl and its analogs (e.g., acetylfentanyl, furanylfentanyl, and carfentanil) have contributed to nearly half of opioid overdose deaths 16 , 30 , 31 . Moreover, the number of deaths that were attributable to illicitly manufactured fentanyl and its analogs nearly quadrupled between July 2015 and June 2017 in Montgomery County, Ohio 32 . Heroin-positive cases declined while methamphetamine-positive cases increased in these victims. Urine drug screens showed that the prevalence of recent fentanyl use in patients who received opioid agonist treatment in England was 3%, and multiple fatalities with synthetic fentanyl analogs were reported in northern England in early 2017 33 , 34 .

Fentanyl is ~30–50 times more potent than heroin, and smaller volumes of heroin and other drugs that are adulterated with fentanyl can produce powerful effects with lower production costs. Detecting fentanyl and its analogs in used syringes can reveal exposure risk 35 . The fentanyl detection rate was significantly higher among drug users who injected drugs in the past 6 months compared with non-injection drug users. The prevalence of non-fatal overdose is very high among people who inject drugs 36 – 38 . The prevalence of intravenous fentanyl use among people who inject drugs in Australia is 8%. Given the narrow range between effective and lethal doses, this population is at high risk of overdose 37 , 39 , 40 . The opioid crisis is likely attributable to illicitly manufactured fentanyl and its analogs around the world, especially when they are mixed with heroin and other drugs, and the route of administration 41 , 42 .

Many people who have survived fentanyl overdose appear to be unaware that they ever took the drug. Surveys from 17 harm reduction sites in British Columbia, Canada, revealed that the prevalence of fentanyl use was 29% (70/242; based on urine drug screen), 73% of whom report that they did not knowingly use fentanyl 43 . Urine drug screens in methadone-maintained patients in Wayne County, Michigan, showed that 38% of 368 unique patients tested positive for fentanyl, and 67.3% of 113 patients reported that they did not know anyone who sought to obtain fentanyl in a subsequent anonymous survey 44 . A high risk of overdose and deaths was found among this vulnerable population that exhibited high fentanyl exposure, thus highlighting the pressing need to develop appropriate harm-reduction strategies, such as surveillance, the development of early-warning systems, pill-testing technology about the presence of fentanyl in various drug products, naloxone training and distribution, overdose education, and urine screens 21 , 45 , 46 . The vast majority of people reported their willingness to use rapid test strips to detect the presence of fentanyl in drugs or urine at home or utilize drug-checking services at supervised injection clinics 47 , 48 . Multiplex ultrahigh-performance liquid chromatography (UHPLC–MS)/liquid chromatography tandem mass spectrometry (LC–MS–MS)/liquid chromatography–quadrupole time-of-flight–mass spectrometry (LC–QTOF–MS) analyses have also been developed and validated for the detection of fentanyl and its analogs and metabolites in blood, hair, and oral fluid, which will be helpful for informing harm reduction behaviors and combating the fentanyl crisis 49 – 52 . A newly developed lateral flow immunoassay was also evaluated for effectiveness in the detection of fentanyl analogs 53 .

Pharmacological mechanisms and side effects of fentanyl

Despite the beneficial clinical anesthetic and pain-relieving effects of fentanyl, the frequent use of fentanyl primarily affects the central nervous system (CNS) and gastrointestinal, cardiovascular, and pulmonary systems and can cause several side effects 54 . Digestive symptoms, such as nausea, vomiting, and constipation, are common in patients who repeatedly use fentanyl 55 , 56 . Immunosuppression was also shown to be precipitated by analgesic opioid drugs, including fentanyl, in preclinical and clinical studies. Such immunosuppression can be especially dangerous in the elderly and already immunocompromised patients 57 – 59 . Additionally, fentanyl and synthetic opioids have other frequently reported side effects, including migraine, dizziness, vertigo, confusion, hallucinations, and a higher risk of fractures in the elderly 59 – 63 . Fentanyl has rewarding effects and thus high abuse potential. Its repeated use leads to the development of tolerance and drug dependence 64 , 65 . Analyses of adverse-event reporting systems in the United States, Europe, and the United Kingdom have shown that cases of fentanyl-related misuse, abuse, dependence, and withdrawal steadily increased between 2004 and 2018, resulting in prolonged hospitalization or death 66 . Other mental disorders, such as depression, insomnia, and suicidality, can also occur with fentanyl abuse, contributing to relapse and a higher risk of respiratory depression or overdose death 65 , 67 . The treatment of these mental disorders may help prevent fentanyl-related fatalities and achieve abstinence.

Fentanyl is a full μ-opioid receptor agonist, but it also acts on δ- and κ-opioid receptors 68 , 69 . Fentanyl has been shown to exert its analgesic and lethal effects through different receptor populations in the CNS. It is eliminated from cerebrospinal fluid at approximately the same rate as morphine 70 , 71 . Acute naloxone administration antagonizes fentanyl-induced analgesia more than fentanyl-induced lethality. β-funaltrexamine was shown to inhibit both fentanyl-induced analgesia and lethality 71 . Overdose-related concentrations of fentanyl were shown to block human ether-a-go-go-related gene (hERG) potassium channels in ventricular myocytes that were isolated from neonatal rats, which may contribute to fentanyl-related overdose death or sudden death 72 .

Respiratory depression is the most dangerous adverse reaction to fentanyl that can result in lethality. In rats, intravenous injections of fentanyl dose-dependently decreased oxygen levels in the nucleus accumbens, basolateral amygdala, and subcutaneous space, followed by a delayed increase in glucose and fluctuations in brain temperature and metabolic brain activity 73 – 75 . Neuronal hypermetabolism that is induced by fentanyl and its analogs may damage the hippocampus and limbic system, causing an amnestic syndrome in patients who use fentanyl 76 – 79 . With regard to brain hypoxia and hypothermia, fentanyl has synergistic effects with heroin, which is consistent with the higher risk of overdose death that is associated with heroin–fentanyl mixtures 73 , 80 . Fentanyl-related respiratory depression is also dose-dependent, which reaches a peak 5 min after administration and requires 4 h to recover in humans. Such effects can lead to prolonged apnea and sudden death 74 , 81 , 82 . Epidural fentanyl infusion has been shown to cause postoperative adult respiratory distress syndrome 83 . The μ 1 -opioid receptor is involved in respiratory depression that is induced by fentanyl and its analogs but not morphine 84 . Selective α4β2 nicotinic receptor agonist A85380 reversed fentanyl-induced respiratory depression in rats without significant side effects 85 . The calcium-activated potassium channel blocker GAL021 was shown to attenuate morphine-induced respiratory depression in rats, mice, and nonhuman primates, and it produced stimulatory effects during alfentanil-induced respiratory depression, without affecting sedation in humans 86 – 88 . However, more studies are needed to confirm the efficacy and potential toxicity of A85380 and GAL021.

Many studies have reported cardiovascular symptoms after fentanyl-induced analgesia, such as myocardial ischemia, QTc interval prolongation, and bradycardia 89 – 91 . Fentanyl is commonly used during percutaneous coronary interventions, but the relative safety of its use requires further investigation because intravenous fentanyl has been reported to induce hypothermia, impair ticagrelor absorption, and cause antiplatelet effects 92 – 94 . Autopsy and toxicological analyses indicated that chronic fentanyl use may be responsible for hypertrophy, cardiac fibrosis, and atherosclerosis 54 , 95 , 96 . Neither sigma nor opioid receptors are essential for the fentanyl-induced attenuation of muscarinic coronary contraction 97 .

Fentanyl administration provides effective pain relief, but its long-term use can result in a lowering of pain thresholds 98 , 99 . This phenomenon of fentanyl-induced hyperalgesia is a challenge in the clinical management of perioperative and chronic pain. Recent studies showed that fentanyl-induced hyperalgesia was modulated by the activation of extracellular signal-regulated kinase in the laterocapsular division of the central nucleus of the amygdala (CeLC) and CaMKIIα in the CeLC–periaqueductal gray–rostral ventromedial medulla–spinal cord descending facilitative pain pathway in rats 100 , 101 .

Interventions for the management and prevention of fentanyl overdose

Similar treatments are prescribed for opioid use disorder and opioid overdose, including the Food and Drug Administration (FDA)-approved medications methadone, buprenorphine, extended-release naltrexone, and naloxone 102 . Lofexidine, a central α 2 -adrenergic receptor agonist, was the first non-opioid medication that was approved by the United States FDA for the treatment of opioid withdrawal 103 , 104 . Lofexidine has fewer prescriptive barriers and comparable efficacy and safety relative to other opioid receptor agonizts, but it is generally more expensive. Sparse data are available on the effectiveness of interventions to prevent overdoses that are caused by illicitly manufactured fentanyl (Table (Table1). 1 ). Compared with other opioid-related overdoses, illicit fentanyl-related overdoses appear to be accompanied by distinct symptoms, such as body and chest rigidity, dyskinesia, and slow or irregular heart rate, which can affect overdose management, such as oxygen provisions and appropriate doses of naloxone 105 , 106 . To avoid or reduce the adverse effects of fentanyl, the FDA proposed to control the duration of use and doses of fentanyl 107 . One study showed that the majority of patients who were presumed to experience fentanyl overdose could be discharged after brief emergency room observation, thus unlikely requiring additional naloxone dosing in the emergency room 108 .

Overview of medications for the treatment of opioid use disorder and potential implications for the treatment of fentanyl overdose

Medication	Mechanism of action	Treatment	Limitations	Implications for fentanyl overdose
Methadone	Full MOR agonist	Reduces cravings and withdrawal symptoms.	Risk of dependence and acute withdrawal after abrupt discontinuation. Respiratory depression and QTc prolongation as a result of methadone overdose or illicit use.	Protects against death and promotes abstinence in fentanyl-exposed patients, but relapse rates are still high.
Buprenorphine	MOR partial agonistKOR antagonist	Reduces cravings and withdrawal symptoms.	Risk of acute withdrawal in OUD patients with high levels of tolerance.	Promotes treatment retention and opioid abstinence in fentanyl-exposed patients.
Extended-release naltrexone	MOR antagonistKOR antagonist	Reduces cravings, promotes abstinence, promotes treatment retention, and prevents relapse.	Requires detoxification before initiating naltrexone treatment.High risk of early induction failure.	Adverse events, including overdoses, did not differ between extended-release naltrexone and buprenorphine-naloxone combination.
Naloxone	MOR antagonist	Reduces craving, promotes abstinence, promotes treatment retention, and prevents relapse.	Risk of precipitating opioid withdrawal.	Mostly utilized to reverse the overdose epidemic, but its efficacy needs improvement, and safe dosing needs further investigation.
Lofexidine	Central α -adrenergic receptor agonist	Reduces withdrawal symptoms but not drug craving.	Hypotension and bradycardia. Not effective for all withdrawal symptoms.	N/A

MOR μ-opioid receptor, KOR κ-opioid receptor, OU D opioid use disorder

There are limited data on the efficacy of methadone or buprenorphine for the treatment of illicit fentanyl use. A retrospective study in Rhode Island showed that 6 months of methadone maintenance protected against death and promoted abstinence in fentanyl-exposed patients, but relapse rates were still high 109 . Buprenorphine is a μ-opioid receptor partial agonist and κ-opioid receptor antagonist that is commonly used to treat opioid use disorder. It also exerts antidepressant and anxiolytic activity and is a promising treatment for neonatal opioid withdrawal syndrome 110 . A retrospective cohort study showed that 6-month treatment retention rates and opioid abstinence rates were not different between individuals who were positive for fentanyl or heroin at baseline before initiating buprenorphine treatment, indicating that buprenorphine may still be beneficial for treating fentanyl exposure 111 . Repeated treatment with buprenorphine produced a greater magnitude of antinociceptive tolerance than higher-efficacy agonizts (e.g., morphine and etonitazene) in rats 112 . Studies in pigeons and rhesus monkeys showed that the amount of tolerance that develops to the reinforcing potency of opioids depends on their efficacy, and the higher-efficacy μ-opioid receptor agonist sufentanil was more difficult to antagonize than the low-efficacy μ-opioid receptor agonist morphine 113 – 115 . These data indicate that buprenorphine may have lower efficacy for the treatment of fentanyl overdose compared with heroin overdose, although no human trials have been performed to date 116 .

Naloxone is a μ-opioid receptor antagonist that is used to treat fentanyl-related overdose, regardless of the suspected route of administration. However, its efficacy is inconsistent, and safe dosing needs to be considered from the perspective of precipitating opioid withdrawal 117 – 119 . Recent studies also showed that extended-release naltrexone was equally safe and effective as a buprenorphine–naloxone combination at promoting abstinence and treatment retention once treatment was initiated, but fewer participants successfully initiated naltrexone treatment 120 , 121 . Larger or repeated doses of naloxone are speculated to be required for the treatment of fentanyl overdose because of its higher affinity for μ-opioid receptors. However, a study of a community naloxone distribution program in Allegheny County showed that the average doses of naloxone that were administered to reverse overdose did not change between 2013 and 2016, although the incidence of overdoses that were related to fentanyl and its analogs increased during the same time 122 . A retrospective study of the fentanyl epidemic in Chicago showed that doses of naloxone up to 12 mg may effectively treat fentanyl overdose 123 . Naloxone was shown to reverse transdermal fentanyl overdose-induced sedation, the reduction of body temperature, and the reduction of heart rate in dogs 124 . A systematic review found a low incidence of mortality or serious adverse events that were caused by prehospital naloxone administration in opioid overdose patients, although the source of overdose was mostly heroin and not fentanyl 125 . Additionally, seeking emergency medical help was positively associated with overdose victims who received higher doses of naloxone and rescue breathing in British Columbia, Canada 126 . A survey of 316 street-recruited people who used opioids in Baltimore showed that the majority of them perceived the high risk of fentanyl-adulterated heroin and overdose, but most of them did not often carry naloxone with them 127 . The early adoption and distribution of take-home naloxone have been reported to effectively prevent opioid overdose deaths 128 – 130 . Therefore, harm reduction strategies, such as safe injection sites, the expansion of available opioid agonist treatment, and overdose prevention training (e.g., carrying naloxone and not use drugs alone, higher dose or multiple administrations of naloxone), are needed to control the adverse effects of fentanyl and reduce overdoses 131 .

Additionally, more potent, longer-acting opioid receptor antagonists are needed to prevent fentanyl-related overdose deaths. Compared with naloxone, nalmefene has been shown to have superior efficacy in reversing the carfentanil-induced loss of righting reflex and respiratory depression in rats 132 . Nalmefene is generally well tolerated and is a recent option for patients with alcohol dependence 133 – 135 . Additionally, novel, selective, and potent μ-opioid receptor antagonists, such as 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3-carboxamido)morphinan (NAQ) and 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(indole-7-carboxamido)morphinan (NAN), have been reported to produce less opioid tolerance, dependence, and withdrawal signs. Furthermore, NAN pretreatment was shown to block the discriminative stimulus effects of fentanyl in rats. The orexin-1 receptor antagonist SB-334867 was also shown to decrease motivation and demand for fentanyl in rats 136 . Therefore, these drugs could be considered candidates for the treatment of opioid use disorder 137 . Chronic anticonvulsant carbamazepine therapy was shown to increase fentanyl clearance and decrease plasma concentrations in neurosurgical patients, which may attenuate the actions of fentanyl 138 . A case report showed that treatment with slow-release oral morphine in a near-fatal fentanyl overdose patient was successful, despite the patient’s previous failures with methadone and buprenorphine/naloxone-based opioid agonist therapies, which could be considered potential alternative treatments 139 .

Previous studies have reported the vaccine consisting of fentanyl hapten conjugated to tetanus toxoid or keyhole limpet hemocyanin carrier protein, and immunization with these vaccines reduced fentanyl biodistribution to the brain, and blunted its antinociceptive effects and respiratory depression in rodents 140 , 141 . Moreover, the conjugate vaccine stimulated the endogenous generation of antibodies with high affinity for a variety of fentanyl analogs 140 , and was shown to blunt fentanyl reinforcement 142 . A recent study screened and purified monoclonal antibodies (mAbs) from vaccinated mice, and found that the 6A4 mAb prevented the acute lethality of fentanyl, and reversed both fentanyl and carfentanil-induced antinociception as effective as naloxone 143 . These findings suggest that immunopharmacotherapies including active vaccine or its combination with passive mAb may be potential and promising treatment strategies to address the current opioid crisis. Accumulating evidence also implicate the dysbiosis of gut microbiome in the pathophysiology of drug addiction, however data regarding fentanyl use is rare 144 . Manipulating the compositions of the gut microbiome or its products may guide new adjuvant therapies for opioid addiction in the future.

A United States FDA Risk Evaluation and Mitigation Strategy (REMS) program was also implemented to assess transmucosal immediate-release fentanyls (TIRFs) and found that substantial rates of TIRFs were prescribed inappropriately 145 , 146 . With the findings of deficiencies in the structure and administration of TIRFs, the development of other REMSs is needed to ensure the safe and appropriate use of approved drugs, especially dangerous opioid drugs 147 .

In conclusion, the crisis of opioid-related overdoses, especially fentanyl and its analogs, is a major threat to both individual and public health. Respiratory depression, cardiovascular effects, and neuropsychiatric symptoms are associated with fentanyl overdose and lethality. Naloxone is the standard rescue drug for fentanyl overdose, but its efficacy is inconsistent. Further clinical research is needed to optimize individualized medication-assisted treatments in patients who overdose on fentanyl and its analogs. To address the social, economic, and health problems that are associated with fentanyl and its analogs, coordinated efforts are needed to implement large-scale harm reduction strategies (e.g., naloxone distribution, innovative studies, and the development of novel drugs).

Acknowledgements

This work was supported in part by the National Natural Science Foundation of China (nos. 81701312 and 81521063).

Conflict of interest

The authors declare that they have no conflict of interest.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The Drug Overdose Problem Essay

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What led to the opioid crisis—and how to fix it

February 9, 2022 – Without urgent intervention, 1.2 million people in the U.S. and Canada will die from opioid overdoses by the end of the decade, in addition to the more than 600,000 who have died since 1999, according to a February 2 report from the Stanford-Lancet Commission on the North American Opioid Crisis. In this Big 3 Q&A, Howard Koh , professor of the practice of public health leadership and a member of the Commission, discusses factors contributing to the crisis and recommendations on how to curb it.

Q: What was the impetus behind this new report on the opioid crisis, and why was it important for this commission to issue the report at this time?

A: The current opioid crisis ranks as one of the most devastating public health catastrophes of our time. It started in the mid-1990s when the powerful agent OxyContin, promoted by Purdue Pharma and approved by the Food and Drug Administration (FDA), triggered the first wave of deaths linked to use of legal prescription opioids. Then came a second wave of deaths from a heroin market that expanded to attract already addicted people. More recently, a third wave of deaths has arisen from illegal synthetic opioids like fentanyl. In addition to the crushing public health burden of preventable deaths, millions more are affected by related problems involving homelessness, joblessness, truancy, and family disruption, for example.

The pandemic has both masked and amplified this crisis. Rising death trends are linked to drivers such as the anxiety and isolation of COVID-19 as well as continued lack of access to quality care and prevention. The crisis seems unchecked. It demands an urgent, unified, and comprehensive response.

Q: What were the main drivers of the opioid crisis, and what are the report’s main takeaways on how to minimize the damage?

A: One major conclusion is that the crisis represents a multi-system failure of regulation. OxyContin approval is one example—Purdue Pharma was later shown to have presented a fraudulent description of the drug as less addictive than other opioids. The profit motive of the pharmaceutical industry remains ever present.

And that’s just the tip of the iceberg. Post-approval, it’s usually left up to industry—not regulators—to educate and advise prescribers on how to evaluate and mitigate risk. Donations from opioid manufacturers to politicians continue to influence policy decisions. In addition, a revolving door of officials leaving government regulatory agencies such as the Drug Enforcement Agency regularly join the pharmaceutical industry with little to no “cooling off” periods. The report details these and other glaring examples.

The report recommends ways to curb pharmaceutical industry influence while also upholding quality care that balances benefits and risks for people with chronic pain. We must continue progress in promoting opioid stewardship—safer prescribing initiatives led by physicians.

Care, treatment, and prevention are all absolutely critical. Currently, addiction care, for example, is not only often separate from mainstream medicine but also unequal. It is also often clouded by stigma, uneven quality, and inaccessibility. Addiction remains a constant long-term threat to human health and won’t respond to only short-term fixes or short-term funding. We have to fully integrate addiction care into mainstream health care, provide enduring and sustained funding, and assure that both public and private insurance cover the full range of addiction services. Parity laws require that most private health plans cover substance use disorder services and not limit them more stringently than services associated with other medical conditions. But such laws are not always followed and that must change.

Addiction training should be an essential part of all health professional education. The public health community can also work with the criminal justice system to move more affected people away from incarceration and towards treatment.

And prevention, starting with kids, is absolutely key. We have to support stronger and more resilient children and families to address threats from opioids, tobacco, alcohol, and other substances that rob so many people of well-being.

Q: When you look at the current state of this crisis, does anything give you hope?

We can see progress in some vital areas. For example, more health professionals are using the term “substance use disorder” instead of “substance abuse” to recognize the condition as a medical and health issue and not a moral failing. And instead of references to people being “clean” or “dirty,” people are increasingly using the medical terms “recovery” and “relapse.” It’s gratifying to see this change in the language of addiction.

The Affordable Care Act has also helped in major ways, starting by requiring that private insurance plans cover substance use disorder services as part of essential health benefits. It also has facilitated expansion of Medicaid, the single largest payer of opioid use disorder services. The report notes that states that have expanded Medicaid eligibility have shown evidence of decreased overdose deaths and increased receipt of treatment.

It is inspiring to celebrate the estimated 25 million people who are in recovery. People in recovery are heroes for me. So many have been able to rebuild relationships with people they care for, contribute again to society, and regain a sense of purpose and meaning in their lives. It may seem to be a hopeless situation but it’s not. In the midst of this terrible crisis, that’s what gives me the greatest hope for the future.

– Karen Feldscher

We Can Prevent Overdose Deaths if We Change How We Think About Them

I ’ve been living in recovery from opioid use disorder for eight and a half years, and this might be a weird thing to say about addiction, but I feel lucky—like I dodged a bullet. I was addicted to opioids in Florida throughout the early 2000s, during the heyday of pill mills that flooded the streets with powerful pharmaceuticals like OxyContin. I say I’m lucky because this was just before the drug supply turned into a toxic sludge of potent fentanyl analogues, mysterious tranquilizers, and deadly counterfeit pills. Sometimes I wonder what it would be like if I were using today. The chances of my survival in these dire conditions would be slim to none.

There’s a saying that “dead people can’t recover,” and I know it’s true. In 2022, an average of 300 Americans died from an overdose every single day. That’s an average of 109,680 human souls. We’re losing far too many people to drugs because America has yet to fully commit to a culture, policy, and strategy focused on overdose prevention.

One of the hardest parts about being an activist is getting people to care about problems that appear distant and far away. It’s all too human to perceive danger as striking someone else, somewhere else. We saw this play out with the COVID-19 pandemic. But we’ve long seen this play out with the overdose crisis in America. In 2017, the federal government declared overdoses a “public health emergency,” and ever since, the death rate has steadily ticked up and up. This was in large part due to the three waves of the “opioid epidemic” and the greed of the Sackler family that peddled OxyContin.

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However, calling this an “opioid epidemic” is to mislabel and misunderstand the actual root of the problem we face: Overdose deaths are preventable; we just haven’t had the tools to efficiently do it—until now. Many users die alone in their homes, apartments, cars, in gas station bathrooms, or on the street. Families and entire communities have been shattered by loss. In a fog of pain, grief, and anger, we’re also losing the plot. The focus of drug policy right now should be on preventing as many fatal overdoses as possible. Instead, America is once again trapped in a disastrous drug war that focuses on punishment and retribution over the goal of saving lives.

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The very word “fentanyl” evokes scary visions of chemical warfare and “weapons of mass destruction.” The fury of living through so much loss has elevated a reactionary tendency to harshly criminalize drug use and reinforce lengthy mandatory minimum sentences. Politicians like Donald Trump, for instance, want to execute drug sellers. During his 2024 presidential campaign announcement, Trump said , “We’re going to be asking everyone who sells drugs, gets caught selling drugs, to receive the death penalty for their heinous acts.” Members of congress and dozens of states are moving toward with enacting harsher drug penalties, despite decades of evidence that severe punishments do little to deter drug use or drug dealing. The rhetoric has gotten so hot that lawmakers have introduced proposals to authorize military force against drug traffickers in Mexico, turning a metaphorical drug war into a literal war of bombing and invasion. Fear, anger, and political expediency are causing us to repeat failed strategies of the past.

But now is not the time to reach for easy answers and give into dark impulses. Instead, we must double down on overdose prevention using a public health and harm reduction framework to equip people who use drugs with practical tools and spaces that destigmatize the life-saving information they need for their journeys to find safety and community.

As someone who has lost well over three dozen people I loved and cared about to overdose deaths, I know how valuable these tools can be. Most of my friends died alone. Many of them were scorned because they returned to drug use. They weren’t offered compassion when they sought healthcare support. Some of them died after being released from jail on a simple possession charge. All of them would have benefitted from the wide availability of harm reduction services such as syringe exchange programs, free naloxone, drug checking equipment that screens for fentanyl analogues, and safer use spaces—without shame, and without judgement. Consistent data from Harvard’s Recovery Research Institute has shown that harm reduction works and is rooted in evidence.

If we don’t correct our current course, we’ll be stuck in this vicious cycle that leaves millions of people sick, alone, and at risk of fatally overdosing.

On March 29, the FDA approved the first-ever over-the-counter (OTC) naloxone product. In July, they approved a second OTC naloxone product. While this is welcome news and a substantial leap forward, the pricing of these products (averaging between $35-$65 per unit ) is still out of reach for everyday Americans who need quick access to the lifesaving overdose reversal medication.

Read More: A Promising Way to Help Drug Users Is ‘Severely Lacking’ Around the World, Report Says

Naloxone should be free. It must be available and accessible everywhere—and for everyone, without any barriers. Most life-saving medical devices are uncontroversial and ubiquitous. It’s time we think about naloxone and overdose reversal the same way we think about EpiPens, defibrillators, vaccines, and testing. Nobody thinks the mere presence of an EpiPen encourages people severely allergic to peanuts to kick back and crush a bag of pistachios for fun. Unlike peanut allergies, addiction remains highly stigmatized. Some are under the false impression that naloxone “encourages” more risky drug use because they view addiction through a moral lens, not a healthcare challenge. This distorted logic, along with Big Pharma profiteering, hinders broad access to naloxone.

While changing policy and regulations is no small thing, changing cultural outlooks is something else entirely. The social scientist and historian Nancy Campbell called naloxone a “technology of solidarity.” For naloxone to work, someone has to be there to administer it to the person who is overdosing. With the recent expansion of naloxone access, it’s on all of us to step up and be ready to save a life. Instead of punishing and scorning those who are struggling, we must do the harder thing and actually show people that they are not alone.

Overdose prevention strategies also require tailored approaches to their culture and geography. Cities and urban centers where substance use is more concentrated can benefit from overdose prevention centers. More than 100 of these centers operate around the world in more than 60 cities. But America only has two that operate legally. The first sanctioned centers on U.S. soil opened in New York in 2021, and they’ve already rescued 1,000 people from fatal overdoses. Just two centers barely meet the demand. A New York City Health Department study found that opening four centers in the city would save up to 130 lives per year while saving $7 million in health care costs. It’s time for other major cities to follow New York’s lead.

Rural areas need a different kind of help covering vast distances. Traveling across the country, I’ve witnessed innovative grassroots overdose prevention solutions in rural towns that operate mobile harm reduction programs. A key tenet of harm reduction is “meeting people where they’re at.” In this case, that means literally. Big vans equipped with naloxone, clean syringes, HIV testing, drug checking, and perhaps most crucially, warm and kind people, are driving around throughout the week to deliver life-saving health care to people who have no other way to access it. Sadly, these programs are operating on shoestring budgets in extremely hostile political climates. Policymakers and communities must stand up and defend these frontline workers who are sacrificing their freedom for doing what they know is right.

You might’ve heard that harm reduction has failed. You might’ve heard that cities like San Francisco and Portland have gone all in on “radical” harm reduction strategies and implemented “pie-in-the-sky” policies like drug decriminalization, and all they have to show for it is death, despair, and abysmal outcomes. The truth is that no American city, not even the supposedly liberal strongholds like San Francisco, have fully committed to a focused strategy of overdose prevention and recovery support. Cutting social and housing services, refusing to reduce skyrocketing rents, all the while ramping up militarized policing is not radical harm reduction. In fact, these half-measures are actively contributing to crisis levels of overdose fatalities.

While politicians and sensational media outlets play up apocalyptic disaster porn, they never mention the success of states like Rhode Island. Rhode Island decided to double-down on overdose prevention and though it’s taken some time, it’s finally starting to pay off. Fentanyl and its potent analogues hit the small state early and hard. For several years, overdose deaths ticked up and up. But something changed. The number of fatal overdoses did not increase from 2021 to 2022. Then, there was a 13% drop in overdose deaths in the second half of 2022. How did they pull it off?

Rhode Island committed fully and firmly to effective overdose prevention strategies. Despite media backlash, they held strong when the going got tough—even when they weren’t sure if it would work. The state implemented mobile outreach programs that distributed harm reduction supplies, increased the availability of naloxone, expanded access to medication assisted treatment for opioid use disorder in jails and prisons, supported six community centers that offer peer-based recovery support services, and created a new evidence-based drug prevention curriculum for schools. Moving forward, Rhode Island will be opening overdose prevention centers like those in New York, which will ensure their fatal overdose trend reversal continues far into the future.

American drug policy is at an inflection point. For the first time in my life, overdose prevention is gaining acceptance as our culture of tough love and zero tolerance is slowly losing credibility. The basic problem we face today is that too many people are dying in isolation, alone in the shadows. The best thing we can do right now is show up for each other, offer compassion to those who are struggling, and stop politicizing something that isn’t political—saving as many lives as possible, with every tool we have at our disposal.

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Review Article
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Published: 11 November 2019

The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies

Ying Han 1 ,
Wei Yan 2 ,
Yongbo Zheng 2 ,
Muhammad Zahid Khan 1 ,
Kai Yuan 2 &
Lin Lu 2 , 3

Translational Psychiatry volume 9 , Article number: 282 ( 2019 ) Cite this article

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Pharmacodynamics

Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients

How μ -opioid receptor recognizes fentanyl

Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies

Introduction.

Fentanyl was first developed in 1960 by Paul Janssen as a potent opioid anesthetic and analgesic. At the time, fentanyl was the fastest-acting opioid discovered to date and more powerful than morphine (50–100 times) and heroin (30–50 times) 1 , 2 . Transdermal, intravenous, and transbuccal fentanyl administration and several other drugs with chemical structures that are similar to fentanyl have been developed, approved, and used for surgical anesthesia and the management of severe cancer pain and perioperative pain, eventually becoming the most often used synthetic opioid in clinical practice 3 , 4 , 5 . Since 1979, fentanyl and its analogs have been synthesized in laboratories and sold as heroin substitutes or mixed with other illicitly sourced drugs, leading to an increase in fentanyl-related overdose deaths 6 , 7 . Postmortem studies have consistently found pulmonary edema, congestion, and needle puncture sites in these victims. Based on data from the National Vital Statistics System, 599,255 drug overdose deaths occurred from 1979 to 2016 in the United States, and the overall mortality rate has seen exponential growth. Fentanyl-related overdose deaths predominantly occurred in the northeastern United States, mostly affecting younger people (20–40 years of age), and grew sharply since 2013 8 .

Rapid death from ingesting fentanyl has become increasingly more common. Its high potency, fast onset of action, and duration of the desired effect may be particularly important contributing factors to the higher risk of overdose deaths and social consequences 9 . Fentanyl has become a major contributor to cocaine-related fatal overdoses. The rate of fentanyl-related overdose deaths increased 55% between 2015 and 2017 in New York city 10 , 11 . Synthetic opioids are also increasingly detected in illicit supplies of heroin, methamphetamine, and counterfeit pills. Analysis of a sampling of 1 million unique patients’ urine drug test (UDT) specimens showed that positivity rates for fentanyl have increased by 1850% among cocaine positive UDT results and increased by 798% among methamphetamine-positive UDT results between January 2013 and September 2018 12 . This mixture may lead to the increases in cocaine-related and methamphetamine-related overdoses. Moreover, the number of fatal overdoses from synthetic opioids, primarily fentanyl and its analogs, was 19,547 in 2016 in the United States, and this rate increased by 88% per year from 2013 to 2016 13 , 14 , 15 , 16 . The incidence of heroin-related overdose deaths stabilized in 2017, whereas deaths that involved other synthetic opioids continued to increase 17 . Given the substantial individual and public health threats of this emerging problem, the present review summarizes the epidemic and evolution of illicit fentanyl use, its pharmacological mechanism of action, its adverse consequences, and the clinical management and prevention of fentanyl-related overdoses.

Epidemic and evolution of illicit fentanyl use

Fentanyl is currently approved and commonly used to treat breakthrough pain in cancer patients and various other clinical conditions that involve noncancer pain, such as postoperative pain. However, its potential for abuse and the rise in overdose deaths pose a serious challenge to public health 18 , 19 , 20 , 21 . Deaths that were attributable to illicit fentanyl use were first reported in the early 1980s and occurred sporadically in the United States 6 , 7 , 22 . A surge in the occurrence of fentanyl-related fatalities among illicit drug users occurred in 2006. A total of 1013 deaths in six states occurred from April 4, 2005, to March 28, 2007 23 . Since then, the prevalence of opioid-related mortality has increased persistently, and the number of reported fentanyl-related deaths more than doubled (from 2628 to 5544) between 2012 and 2014 21 , 24 , 25 . The rate of fentanyl-related overdose deaths increased from <15% in 2010 to ~50% in 2017 in Marion County, Indiana 26 . Overall overdose deaths and first-responder calls increased in a community-based sample in an impoverished neighborhood in Vancouver, Canada, in 2017, and fentanyl was detected in 52% of the subjects who were prescribed opioid agonist therapy 27 . At the same time, fentanyl-related deaths also increased in Australia 28 , 29 .

Fentanyl is ~30–50 times more potent than heroin, and smaller volumes of heroin and other drugs that are adulterated with fentanyl can produce powerful effects with lower production costs. Detecting fentanyl and its analogs in used syringes can reveal exposure risk 35 . The fentanyl detection rate was significantly higher among drug users who injected drugs in the past 6 months compared with non-injection drug users. The prevalence of non-fatal overdose is very high among people who inject drugs 36 , 37 , 38 . The prevalence of intravenous fentanyl use among people who inject drugs in Australia is 8%. Given the narrow range between effective and lethal doses, this population is at high risk of overdose 37 , 39 , 40 . The opioid crisis is likely attributable to illicitly manufactured fentanyl and its analogs around the world, especially when they are mixed with heroin and other drugs, and the route of administration 41 , 42 .

Many people who have survived fentanyl overdose appear to be unaware that they ever took the drug. Surveys from 17 harm reduction sites in British Columbia, Canada, revealed that the prevalence of fentanyl use was 29% (70/242; based on urine drug screen), 73% of whom report that they did not knowingly use fentanyl 43 . Urine drug screens in methadone-maintained patients in Wayne County, Michigan, showed that 38% of 368 unique patients tested positive for fentanyl, and 67.3% of 113 patients reported that they did not know anyone who sought to obtain fentanyl in a subsequent anonymous survey 44 . A high risk of overdose and deaths was found among this vulnerable population that exhibited high fentanyl exposure, thus highlighting the pressing need to develop appropriate harm-reduction strategies, such as surveillance, the development of early-warning systems, pill-testing technology about the presence of fentanyl in various drug products, naloxone training and distribution, overdose education, and urine screens 21 , 45 , 46 . The vast majority of people reported their willingness to use rapid test strips to detect the presence of fentanyl in drugs or urine at home or utilize drug-checking services at supervised injection clinics 47 , 48 . Multiplex ultrahigh-performance liquid chromatography (UHPLC–MS)/liquid chromatography tandem mass spectrometry (LC–MS–MS)/liquid chromatography–quadrupole time-of-flight–mass spectrometry (LC–QTOF–MS) analyses have also been developed and validated for the detection of fentanyl and its analogs and metabolites in blood, hair, and oral fluid, which will be helpful for informing harm reduction behaviors and combating the fentanyl crisis 49 , 50 , 51 , 52 . A newly developed lateral flow immunoassay was also evaluated for effectiveness in the detection of fentanyl analogs 53 .

Pharmacological mechanisms and side effects of fentanyl

Despite the beneficial clinical anesthetic and pain-relieving effects of fentanyl, the frequent use of fentanyl primarily affects the central nervous system (CNS) and gastrointestinal, cardiovascular, and pulmonary systems and can cause several side effects 54 . Digestive symptoms, such as nausea, vomiting, and constipation, are common in patients who repeatedly use fentanyl 55 , 56 . Immunosuppression was also shown to be precipitated by analgesic opioid drugs, including fentanyl, in preclinical and clinical studies. Such immunosuppression can be especially dangerous in the elderly and already immunocompromised patients 57 , 58 , 59 . Additionally, fentanyl and synthetic opioids have other frequently reported side effects, including migraine, dizziness, vertigo, confusion, hallucinations, and a higher risk of fractures in the elderly 59 , 60 , 61 , 62 , 63 . Fentanyl has rewarding effects and thus high abuse potential. Its repeated use leads to the development of tolerance and drug dependence 64 , 65 . Analyses of adverse-event reporting systems in the United States, Europe, and the United Kingdom have shown that cases of fentanyl-related misuse, abuse, dependence, and withdrawal steadily increased between 2004 and 2018, resulting in prolonged hospitalization or death 66 . Other mental disorders, such as depression, insomnia, and suicidality, can also occur with fentanyl abuse, contributing to relapse and a higher risk of respiratory depression or overdose death 65 , 67 . The treatment of these mental disorders may help prevent fentanyl-related fatalities and achieve abstinence.

Respiratory depression is the most dangerous adverse reaction to fentanyl that can result in lethality. In rats, intravenous injections of fentanyl dose-dependently decreased oxygen levels in the nucleus accumbens, basolateral amygdala, and subcutaneous space, followed by a delayed increase in glucose and fluctuations in brain temperature and metabolic brain activity 73 , 74 , 75 . Neuronal hypermetabolism that is induced by fentanyl and its analogs may damage the hippocampus and limbic system, causing an amnestic syndrome in patients who use fentanyl 76 , 77 , 78 , 79 . With regard to brain hypoxia and hypothermia, fentanyl has synergistic effects with heroin, which is consistent with the higher risk of overdose death that is associated with heroin–fentanyl mixtures 73 , 80 . Fentanyl-related respiratory depression is also dose-dependent, which reaches a peak 5 min after administration and requires 4 h to recover in humans. Such effects can lead to prolonged apnea and sudden death 74 , 81 , 82 . Epidural fentanyl infusion has been shown to cause postoperative adult respiratory distress syndrome 83 . The μ 1 -opioid receptor is involved in respiratory depression that is induced by fentanyl and its analogs but not morphine 84 . Selective α4β2 nicotinic receptor agonist A85380 reversed fentanyl-induced respiratory depression in rats without significant side effects 85 . The calcium-activated potassium channel blocker GAL021 was shown to attenuate morphine-induced respiratory depression in rats, mice, and nonhuman primates, and it produced stimulatory effects during alfentanil-induced respiratory depression, without affecting sedation in humans 86 , 87 , 88 . However, more studies are needed to confirm the efficacy and potential toxicity of A85380 and GAL021.

Many studies have reported cardiovascular symptoms after fentanyl-induced analgesia, such as myocardial ischemia, QTc interval prolongation, and bradycardia 89 , 90 , 91 . Fentanyl is commonly used during percutaneous coronary interventions, but the relative safety of its use requires further investigation because intravenous fentanyl has been reported to induce hypothermia, impair ticagrelor absorption, and cause antiplatelet effects 92 , 93 , 94 . Autopsy and toxicological analyses indicated that chronic fentanyl use may be responsible for hypertrophy, cardiac fibrosis, and atherosclerosis 54 , 95 , 96 . Neither sigma nor opioid receptors are essential for the fentanyl-induced attenuation of muscarinic coronary contraction 97 .

Interventions for the management and prevention of fentanyl overdose

Similar treatments are prescribed for opioid use disorder and opioid overdose, including the Food and Drug Administration (FDA)-approved medications methadone, buprenorphine, extended-release naltrexone, and naloxone 102 . Lofexidine, a central α 2 -adrenergic receptor agonist, was the first non-opioid medication that was approved by the United States FDA for the treatment of opioid withdrawal 103 , 104 . Lofexidine has fewer prescriptive barriers and comparable efficacy and safety relative to other opioid receptor agonizts, but it is generally more expensive. Sparse data are available on the effectiveness of interventions to prevent overdoses that are caused by illicitly manufactured fentanyl (Table 1 ). Compared with other opioid-related overdoses, illicit fentanyl-related overdoses appear to be accompanied by distinct symptoms, such as body and chest rigidity, dyskinesia, and slow or irregular heart rate, which can affect overdose management, such as oxygen provisions and appropriate doses of naloxone 105 , 106 . To avoid or reduce the adverse effects of fentanyl, the FDA proposed to control the duration of use and doses of fentanyl 107 . One study showed that the majority of patients who were presumed to experience fentanyl overdose could be discharged after brief emergency room observation, thus unlikely requiring additional naloxone dosing in the emergency room 108 .

There are limited data on the efficacy of methadone or buprenorphine for the treatment of illicit fentanyl use. A retrospective study in Rhode Island showed that 6 months of methadone maintenance protected against death and promoted abstinence in fentanyl-exposed patients, but relapse rates were still high 109 . Buprenorphine is a μ-opioid receptor partial agonist and κ-opioid receptor antagonist that is commonly used to treat opioid use disorder. It also exerts antidepressant and anxiolytic activity and is a promising treatment for neonatal opioid withdrawal syndrome 110 . A retrospective cohort study showed that 6-month treatment retention rates and opioid abstinence rates were not different between individuals who were positive for fentanyl or heroin at baseline before initiating buprenorphine treatment, indicating that buprenorphine may still be beneficial for treating fentanyl exposure 111 . Repeated treatment with buprenorphine produced a greater magnitude of antinociceptive tolerance than higher-efficacy agonizts (e.g., morphine and etonitazene) in rats 112 . Studies in pigeons and rhesus monkeys showed that the amount of tolerance that develops to the reinforcing potency of opioids depends on their efficacy, and the higher-efficacy μ-opioid receptor agonist sufentanil was more difficult to antagonize than the low-efficacy μ-opioid receptor agonist morphine 113 , 114 , 115 . These data indicate that buprenorphine may have lower efficacy for the treatment of fentanyl overdose compared with heroin overdose, although no human trials have been performed to date 116 .

Naloxone is a μ-opioid receptor antagonist that is used to treat fentanyl-related overdose, regardless of the suspected route of administration. However, its efficacy is inconsistent, and safe dosing needs to be considered from the perspective of precipitating opioid withdrawal 117 , 118 , 119 . Recent studies also showed that extended-release naltrexone was equally safe and effective as a buprenorphine–naloxone combination at promoting abstinence and treatment retention once treatment was initiated, but fewer participants successfully initiated naltrexone treatment 120 , 121 . Larger or repeated doses of naloxone are speculated to be required for the treatment of fentanyl overdose because of its higher affinity for μ-opioid receptors. However, a study of a community naloxone distribution program in Allegheny County showed that the average doses of naloxone that were administered to reverse overdose did not change between 2013 and 2016, although the incidence of overdoses that were related to fentanyl and its analogs increased during the same time 122 . A retrospective study of the fentanyl epidemic in Chicago showed that doses of naloxone up to 12 mg may effectively treat fentanyl overdose 123 . Naloxone was shown to reverse transdermal fentanyl overdose-induced sedation, the reduction of body temperature, and the reduction of heart rate in dogs 124 . A systematic review found a low incidence of mortality or serious adverse events that were caused by prehospital naloxone administration in opioid overdose patients, although the source of overdose was mostly heroin and not fentanyl 125 . Additionally, seeking emergency medical help was positively associated with overdose victims who received higher doses of naloxone and rescue breathing in British Columbia, Canada 126 . A survey of 316 street-recruited people who used opioids in Baltimore showed that the majority of them perceived the high risk of fentanyl-adulterated heroin and overdose, but most of them did not often carry naloxone with them 127 . The early adoption and distribution of take-home naloxone have been reported to effectively prevent opioid overdose deaths 128 , 129 , 130 . Therefore, harm reduction strategies, such as safe injection sites, the expansion of available opioid agonist treatment, and overdose prevention training (e.g., carrying naloxone and not use drugs alone, higher dose or multiple administrations of naloxone), are needed to control the adverse effects of fentanyl and reduce overdoses 131 .

Additionally, more potent, longer-acting opioid receptor antagonists are needed to prevent fentanyl-related overdose deaths. Compared with naloxone, nalmefene has been shown to have superior efficacy in reversing the carfentanil-induced loss of righting reflex and respiratory depression in rats 132 . Nalmefene is generally well tolerated and is a recent option for patients with alcohol dependence 133 , 134 , 135 . Additionally, novel, selective, and potent μ-opioid receptor antagonists, such as 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3-carboxamido)morphinan (NAQ) and 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(indole-7-carboxamido)morphinan (NAN), have been reported to produce less opioid tolerance, dependence, and withdrawal signs. Furthermore, NAN pretreatment was shown to block the discriminative stimulus effects of fentanyl in rats. The orexin-1 receptor antagonist SB-334867 was also shown to decrease motivation and demand for fentanyl in rats 136 . Therefore, these drugs could be considered candidates for the treatment of opioid use disorder 137 . Chronic anticonvulsant carbamazepine therapy was shown to increase fentanyl clearance and decrease plasma concentrations in neurosurgical patients, which may attenuate the actions of fentanyl 138 . A case report showed that treatment with slow-release oral morphine in a near-fatal fentanyl overdose patient was successful, despite the patient’s previous failures with methadone and buprenorphine/naloxone-based opioid agonist therapies, which could be considered potential alternative treatments 139 .

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This work was supported in part by the National Natural Science Foundation of China (nos. 81701312 and 81521063).

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Han, Y., Yan, W., Zheng, Y. et al. The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies. Transl Psychiatry 9 , 282 (2019). https://doi.org/10.1038/s41398-019-0625-0

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Opioid Crisis in the US Essay

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Opioid misuse is considered to be a major health problem in the US and a leading cause of injury-related death. The rate of overdose death related to the use of opioids has drastically increased over the last couple of decades (Centers for Disease Control and Prevention, 2019). Opioid-related overdose death rates and prescribing rates vary widely across different states. West Virginia’s opioid-related overdose death rate of 43.40 was one of the highest in the US in 2016 (Scholl, Seth, Kariisa, Wilson, & Baldwin, 2018, p. 1422). This is threefold higher than the national opioid-related overdose death rate of 13.3 in 2016 with a total of 42,249 drug overdose deaths (Scholl et al., 2018, p. 1422).

In turn, West Virginia’s drug overdose death rate involving prescription opioids is 19.7, whereas the national average is just 5.2. In 2015, West Virginia healthcare providers wrote 110 opioid prescriptions for 100 persons, compared to the average US rate of 70.6 prescriptions (Centers for Disease Control and Prevention, 2018, para. 8). Alarming rates for West Virginia highlight the need to mobilize a national and state response to the opioid epidemic.

Three types of prevention interventions have been identified in order to decrease the alarming opioid crisis with its staggering death rates. Primary prevention intervention focuses on opioid misuse prevention before it even occurs. A good example of such an intervention is dissemination and implementation of prevention programs that promote safe storage and disposal of opioids. It is assumed that prevention programs offered to teenagers and adolescents can effectively reduce the misuse of opioids in the selected population. These programs can be delivered in various settings and tailored to the attributes of specific communities. This intervention may be of particular importance to young people as individuals usually initiate drugs misuse when they are under the age of 18.

Secondary prevention intervention that could be considered is screening for opioid misuse. Routine screening for drug misuse using the opioid-risk tools can assess clinical risk for opioid abuse among people who are prescribed opioids. It may be assumed that screening can reduce opioid-related overdose death rates and address opioid prescription rates. Tertiary prevention intervention relates to the specific intervention that reduces harm or consequences of opioid misuse for individuals who already have a drug misuse disorder. An example of such an intervention may be the treatment of opioid use disorders and the provision of naloxone to prevent opioid-related overdose death.

The evidence-based strategy that could effectively reduce provider opioid prescription rates is the prescription drug monitoring programs (PDMPs). PDMPs are electronic databases that collect, analyze, and monitor prescriptions written to individuals on a state level. Pharmacies and dispensing practitioners submit the data to the PDMPs, and healthcare providers can access them to see patients’ prescribing histories.

Policies may be implemented to require that healthcare providers check their state PDMPs to inform their prescribing decisions. Thus, the main stakeholders charged with addressing the opioid crisis in my community are pharmacists, healthcare providers, and dispensing practitioners. There is evidence that the implementation of such intervention can improve opioid prescribing and protect patients who are at risk (Bao et al., 2016). Apart from reducing the use of multiple healthcare providers, the implementation of PDMPs can reduce opioid-related overdose death rates. It is worth mentioning that PDMPs are active databases that can be utilized by the health department to plan and evaluate interventions.

Bao, Y., Pan, Y., Taylor, A., Radakrishnan, S., Luo, F., Pincus, H. A., & Schackman, B. R. (2016). Prescription drug monitoring programs are associated with sustained reductions in opioid prescribing by physicians. Health Affairs , 35 (6), 1045–1051.

Centers for Disease Control and Prevention. (2018). U.S. opioid prescribing rate maps. Web.

Centers for Disease Control and Prevention. (2019). CDC’s response to the opioid overdose epidemic. Web.

Scholl, L., Seth, P., Kariisa, M., Wilson, N., & Baldwin, G. (2018). Drug and opioid-involved overdose deaths — United States, 2013–2017. Morbidity and Mortality Weekly Report , 67 (5152), 1419–1427.

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Introduction
Conclusions
Article Information

Percentages were generated from responses among a nationally representative sample of US adults surveyed in 2023 and incorporate survey weights to adjust for nonresponse (n = 2326). Error bars represent 95% CIs.

Model was adjusted for sociodemographic characteristics. The sample included 2287 individuals. Error bars represent 95% CIs.

Model was adjusted for sociodemographic characteristics. The sample included 817 Democrats, 562 Republicans, and 888 individuals with an independent or no affiliation. Error bars represent 95% CIs.

a Significant difference in viewing addiction as a very or extremely important policy priority among those who have or have not experienced personal overdose loss after adjusting for covariates.

eTable 1. Comparison of Study Sample to National Data

eTable 2. Association Between Personal Overdose Loss and Sociodemographic Characteristics and the Probability of Viewing Addiction as an Extremely or Very Important Policy Issue

eTable 3. Association Between Loss of Family Member or Close Friend to Drug Overdose and Sociodemographic Characteristics and the Probability of Viewing Addiction as an Extremely or Very Important Policy Issue

eTable 4. Stratified Models Estimating the Relationship Between Personal Overdose Loss and Viewing Addiction as an Extremely or Very Important Policy Issue Separately by Political Party Affiliation

eTable 5. Logistic Regression Model Estimating Whether Relationship Between Personal Overdose Loss and Viewing Addiction as an Extremely or Very Important Policy Issue Varies by Political Party Affiliation by Testing Significance of Interaction Terms

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Kennedy-Hendricks A , Ettman CK , Gollust SE, et al. Experience of Personal Loss Due to Drug Overdose Among US Adults. JAMA Health Forum. 2024;5(5):e241262. doi:10.1001/jamahealthforum.2024.1262

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Experience of Personal Loss Due to Drug Overdose Among US Adults

1 Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
2 Division of Health Policy and Management, University of Minnesota School of Public Health, Minneapolis
3 Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
4 Department of Epidemiology and Department of Global Health, Boston University School of Public Health, Boston, Massachusetts
5 de Beaumont Foundation, Bethesda, Maryland
6 Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts

Question What is the magnitude of personal overdose loss (ie, knowing someone who died of a drug overdose) in the US, and what are the policy implications of this loss?

Findings In this cross-sectional study of 2326 US adults, 32% reported knowing someone who died of a drug overdose. Experiencing personal overdose loss was associated with greater odds of endorsement of addiction as an important policy issue.

Meaning The findings suggest that mobilizing the large portion of the US population that has experienced drug overdose loss may be an avenue to facilitating greater policy change.

Importance Since 1999, over 1 million people have died of a drug overdose in the US. However, little is known about the bereaved, meaning their family, friends, and acquaintances, and their views on the importance of addiction as a policy priority.

Objectives To quantify the scope of the drug overdose crisis in terms of personal overdose loss (ie, knowing someone who died of a drug overdose) and to assess the policy implications of this loss.

Design, Setting, and Participants This cross-sectional study used data from a nationally representative survey of US adults (age ≥18 years), the fourth wave of the COVID-19 and Life Stressors Impact on Mental Health and Well-Being (CLIMB) study, which was conducted from March to April 2023.

Main Outcomes and Measures Respondents reported whether they knew someone who died of a drug overdose and the nature of their relationship with the decedent(s). They also reported their political party affiliation and rated the importance of addiction as a policy issue. Logistic regression models estimated the associations between sociodemographic characteristics and political party affiliation and the probability of experiencing a personal overdose loss and between the experience of overdose loss and the perceived salience of addiction as a policy issue. Survey weights adjusted for sampling design and nonresponse.

Results Of the 7802 panelists invited to participate, 2479 completed the survey (31.8% response rate); 153 were excluded because they did not know whether they knew someone who died of a drug overdose, resulting in a final analytic sample of 2326 (51.4% female; mean [SD] age, 48.12 [0.48] years). Of these respondents, 32.0% (95% CI, 28.8%-34.3%) reported any personal overdose loss, translating to 82.7 million US adults. A total of 18.9% (95% CI, 17.1%-20.8%) of all respondents, translating to 48.9 million US adults, reported having a family member or close friend die of drug overdose. Personal overdose loss was more prevalent among groups with lower income (<$30 000: 39.9%; ≥$100 000: 26.0%). The experience of overdose loss did not differ across political party groups (Democrat: 29.0%; Republican: 33.0%; independent or none: 34.2%). Experiencing overdose loss was associated with a greater odds of viewing addiction as an extremely or very important policy issue (adjusted odds ratio, 1.37; 95% CI, 1.09-1.72) after adjustment for sociodemographic and geographic characteristics and political party affiliation.

Conclusions and Relevance This cross-sectional study found that 32% of US adults reported knowing someone who died of a drug overdose and that personal overdose loss was associated with greater odds of endorsing addiction as an important policy issue. The findings suggest that mobilization of this group may be an avenue to facilitate greater policy change.

Drug overdose continues to be one of the most severe and long-lasting public health crises in the US. Since 1999, more than 1 million people have died from a drug overdose, with overdose death totals reaching more than 100 000 annually in 2021 and 2022. 1 , 2 Overdose is a contributor to the marked declines in life expectancy in the US, a trend beginning prior to the COVID-19 pandemic. 3 Opioids are involved in most overdose deaths, with the proliferation of powerful synthetic opioids like fentanyl and polysubstance use accelerating the rising rate of overdose deaths in recent years. 2 , 4

While the economic costs of the overdose crisis are estimated to exceed $1 trillion annually in the US, 5 a more comprehensive accounting of the costs, particularly the effects of these deaths on loved ones and community members, is needed. Unexpected or sudden deaths of loved ones may lead to financial strain, lower productivity, weakened social ties, loneliness, and diminished health across the life course. 6 , 7 However, limited research has explored the consequences of bereavement specifically due to drug overdose. One recent longitudinal study found that children with a parent who died of a drug overdose had increasing rates of mental health treatment in the years following this death. 8 For family members or friends of the decedent, the experience of death from overdose may also be exacerbated by the stigmatized nature of overdose. 9 , 10 Research on the effects of the overdose crisis on broader social networks and communities is limited in part by the methodologic challenges of distinguishing the causal effects of the overdose crisis from endogenous factors contributing to a community’s existing risk of addiction and overdose. Areas of the US that have been disproportionately affected by the overdose crisis face social and economic challenges 11 - 13 ; while it may be likely that these challenges worsen in the face of heightened overdose rates, empirical evidence is lacking.

Capturing the magnitude of the overdose crisis through the lens of personal overdose loss (ie, knowing someone who died of a drug overdose) can also inform understanding of the politics of this issue. 14 The loved ones of individuals affected by major health issues can form powerful political constituencies that organize, build interest groups, and advocate for policy change. 15 Prior research on the politics of the overdose crisis has primarily focused on the relationship between community overdose rates and life expectancy declines and voting behavior. 16 - 21 An underlying assumption of these studies was that the overdose crisis drove voters in highly affected areas rightward on the political spectrum in recent elections. However, a study using individual-level data found no association between perceptions of the local severity of the overdose crisis and voting behavior in the 2018 midterm elections. 20 To our knowledge, missing from this body of research is data on whether the overdose crisis intersects with individuals’ political party identification. Although extreme political polarization currently exists, it is unknown whether the experience of personal overdose loss differs across political party groups and how this might affect perceived salience of drug overdose as a policy issue.

Limited research has quantified the number of US individuals affected by drug overdose in terms of personal overdose loss, the relational nature of that loss (eg, death of a family member, friend, or acquaintance), and the characteristics of those who have experienced a personal overdose loss. Recent data reported that 9% of US adults had a family member die of a drug overdose and that 16% had a family member who had experienced a nonfatal drug overdose. 22 More fully characterizing this experience of personal overdose loss among US adults’ wider networks of family, friends, and acquaintances can reveal the broader scope of this crisis.

Using data from a nationally representative survey of US adults conducted in 2023, this study sought to quantify the scale of the drug overdose crisis in terms of personal overdose loss, the relational nature of that loss, and the characteristics of US adults affected by the experience of personal overdose loss, including political party affiliation. This study also considered the political implications of personal overdose loss by assessing whether this experience is associated with greater salience of overdose as a public policy priority and whether salience of this issue differs across political party groups.

This cross-sectional study analyzed survey data from a nationally representative sample of US adults aged 18 years or older and followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline. The data were derived from the fourth wave of the COVID-19 and Life Stressors Impact on Mental Health and Well-Being (CLIMB) study, 23 , 24 an ongoing longitudinal survey of a representative sample of US adults that began in March 2020 to assess the association between social and economic stressors and mental health and well-being. In the fourth wave, 2 new questions were added to the CLIMB survey instrument regarding respondents’ experience of personal overdose loss. CLIMB study participants were sampled from the NORC AmeriSpeak standing panel in March 2020, with a replenishment sample drawn from the AmeriSpeak panel in this fourth wave. The overall AmeriSpeak panel was constructed using probability-based methods from an address-based sampling frame encompassing 97% of US households; it is commonly used to derive nationally representative estimates in health-related survey research. 25 - 27 The fourth wave of the CLIMB survey was fielded from March 28 to April 17, 2023. Of the 7802 panelists invited to participate in this wave, 2479 completed the survey (31.8% response rate). Panelists provided electronic informed consent before initiating the survey. eAppendix 1 in Supplement 1 describes the comparability of this sample with Current Population Survey benchmarks. This study was approved by the Johns Hopkins institutional review board.

The key variable of interest was whether the respondent had any personal overdose loss. We adapted 2 questions from a 2015 Kaiser Health Tracking Poll 28 : “Do you personally know anyone who has died from a drug overdose?” Respondents could answer “yes,” “no,” or “don’t know.” We excluded respondents who answered “don’t know” from our analysis. Respondents who answered “yes” were then asked, “Who do you know that has died from a drug overdose?” Response options were nonexclusive and included “a family member,” “a close friend,” or “an acquaintance.” A secondary outcome of interest measured whether respondents viewed addiction as a public policy priority. Respondents were asked whether addressing drug addiction should be an extremely important priority, a very important priority, a somewhat important priority, or not an important priority to address. We dichotomized this measure, coding responses that addressing drug addiction should be an extremely important or very important priority as 1 and the remaining response options as 0.

Sociodemographic information encompassed measures collected by AmeriSpeak on all panelists, including age, sex, 9-level census division of residence, race and ethnicity, educational level, annual household income, homeowner status, and marital status. Race and ethnicity were self-reported and analyzed because they are important social categories associated with patterns of drug overdose risk. Categories included Hispanic, non-Hispanic Black, non-Hispanic White, and non-Hispanic other (those who identified as ≥2 racial identities or as Asian). The CLIMB survey also included questions regarding respondents’ current health insurance coverage and financial status relative to 1 year previously. The latter was measured using a question adapted from the Survey of Consumer Attitudes and Behavior, 29 which asked, “Would you say that in comparison to a year ago, you and your family living in your household are financially better off, about the same, or worse off now?” We constructed a binary measure of financial well-being and coded respondents reporting being “worse off now” as 1 and respondents who were financially “better off” or “about the same” as 0. To capture political party affiliation, the CLIMB survey used a question modified from the Pew Research Center that asked, “Do you consider yourself a Democrat, a Republican, an independent, or none of these?” In regression models, we collapsed the response options “independent” and “none of these” into a single category.

First, we calculated the percentage of respondents who reported experiencing any personal overdose loss (regardless of the nature of the relationship) and calculated separately the percentages of respondents who reported having a family member or close friend vs an acquaintance who died of a drug overdose. We multiplied these percentages by the total number of US adults aged 18 years or older reported in the 2020 US census (n = 258 343 281) to estimate the numbers of US adults who had experienced a personal overdose loss. Pearson χ 2 tests of differences in row proportions were used to assess unadjusted differences across sociodemographic, geographic, and political party groups in the experience of any personal overdose loss. Survey weights were used in all analyses to adjust for sampling design and nonresponse.

A logistic regression model estimated the association between the aforementioned sociodemographic and political characteristics and the odds of experiencing a personal overdose loss. We also used a logistic regression model to estimate the probability of viewing addiction as an extremely or very important priority as a function of the experience of personal overdose loss, sociodemographic characteristics, and political party affiliation. In a sensitivity analysis, we replaced any personal overdose loss with a variable capturing whether the respondent experienced the death specifically of a family member or close friend. To test whether the strength of the association between personal overdose loss and viewing addiction as an extremely or very important priority varied by political party affiliation, we interacted the 3-category measure of political party affiliation with the binary measure of experiencing a personal overdose loss. We then used postestimation margins to calculate the adjusted mean probabilities within each political party group by personal overdose loss status.

All statistical analyses were conducted using Stata SE, version 14.2 (StataCorp LLC) and used the Stata survey estimation feature to adjust for sampling design and nonresponse. Two-sided P < .05 was considered significant.

Of 2479 individuals who completed the CLIMB survey, 153 were excluded because they did not know whether they knew someone who died of a drug overdose, resulting in a final analytic sample of 2326. Of these individuals, 52.4% were female and 48.6% were male; mean (SD) age was 48.12 (0.48) years. A total of 11.8% were Black; 17.0%, Hispanic; 62.1%, White; and 9.0%, other race. Across demographic benchmarks, this sample of US adults was similar to adults in the Current Population Survey data 30 (eTable 1 in Supplement 1 ), providing evidence of the national representativeness of this sample. Of the respondents 32.0% (95% CI, 28.8%-34.3%) reported any personal overdose loss, translating to 82.7 million affected US adults ( Figure 1 ). A total of 18.9% (95% CI, 17.1%-20.8%) of respondents, or 48.9 million US adults, reported that a family member or close friend died of a drug overdose, and 16.6% (95% CI, 14.9%-18.4%), or 42.8 million US adults, reported that an acquaintance died of a drug overdose.

The Table displays the unadjusted characteristics of US adults who had and had not experienced a personal overdose loss and the adjusted odds of experiencing personal overdose loss as a function of these characteristics. Personal overdose loss was most prevalent among adults aged 45 to 54 years (37.1%) and 55 to 64 years (36.7%); White adults (36.4%); households with annual income below $30 000 (39.9% vs 26.0% for income≥$100 000); individuals who were widowed, divorced, or separated (43.6%); Medicaid enrollees (51.3%); residents of nonmetropolitan areas (39.6%); and respondents reporting a worsening financial situation over the past year (41.3%). The experience of personal overdose loss was also most prevalent among respondents living in the New England region (44.5%). Notably, there were no differences in personal overdose loss by political party affiliation (Democrat: 29.0%; Republican: 33.0%; independent or none: 34.2%). Unadjusted differences by sex and educational level were not significant. These patterns were generally consistent in the regression model adjusting for covariates. No difference was found in the probability of experiencing personal overdose loss across political party groups even after adjusting for sociodemographic and geographic characteristics ( Table and Figure 2 ).

The experience of any personal overdose loss was associated with greater odds of viewing addiction as an extremely or very important policy issue (adjusted odds ratio [AOR], 1.37; 95% CI, 1.09-1.72) after adjusting for sociodemographic and geographic characteristics and political party affiliation. Full regression model results are displayed in eTable 2 in Supplement 1 . In a sensitivity analysis testing the association between experiencing the death of a family member or close friend from drug overdose and views on addiction as a policy priority, the AOR was directionally consistent but no longer significant (1.26; 95% CI, 0.96-1.66) (eTable 3 in Supplement 1 ). Figure 3 displays the differences in the adjusted mean probabilities of viewing addiction as a policy priority among those with and without any personal overdose loss across respondents affiliated with different political parties. While larger proportions of those who had experienced a personal overdose loss viewed addiction as a policy priority within all political party groups, after adjusting for covariates, only among Democrats was there a significant association between experiencing a personal overdose loss and viewing addiction as a policy priority. Full regression model results are shown in eTable 4 in Supplement 1 . However, no significant differences were found in the strength of this association across political party groups in the model when formally testing for differences in a regression model interacting personal overdose loss with political party affiliation (eTable 5 in Supplement 1 ).

This cross-sectional study of data from a nationally representative survey of US adults found that an estimated 82.7 million US adults have known someone who died of a drug overdose, including 49 million who experienced the death of a family member or close friend. Notably, we found no difference in the experience of personal overdose loss by political party affiliation.

The findings suggest that drug overdose is an issue that affects a substantial proportion of US residents and that knowing someone who died of a drug overdose may be associated with moderately greater propensity to view addiction as a very or extremely important policy priority. That this large group of bereaved US adults, who are not as visible as other communities defined by less stigmatized health issues, 31 reported this issue as a policy priority suggests the potential for this group to be more engaged in policy advocacy at the federal, state, or local level. There was no association between personal overdose loss of a family member or close friend and viewing addiction as a policy priority. On the one hand, we might expect individuals with more intimate relationships with individuals who died of drug overdose to feel more strongly about the need for policy change. On the other hand, research suggests having a personal relationship with an individual with substance use disorder does not always translate to lower levels of stigma. 32 , 33 Family members and close friends may experience courtesy stigma, 34 meaning public disapproval and discrimination due to their close association with members of a stigmatized group. 10 , 35 , 36 To avoid or minimize courtesy stigma, some family members and close friends may distance themselves from the stigmatized issue, which could involve deemphasizing its importance as a policy issue. Nevertheless, efforts to strengthen support for policy change should consider the role of bereaved populations. Prior communication research has found that personal stories told from the perspective of an affected family member may increase receptiveness to public health–oriented drug policy. 37 , 38 This group also may be an underrecognized audience for communication about potential policy strategies.

Despite no differences in the experience of personal overdose loss across political party groups, our findings suggested an association between experiencing any personal overdose loss and viewing addiction as an important policy issue among the subgroup of respondents identifying as Democrats but not among the subgroups of Republicans or independents. However, base levels of endorsement of addiction as an important policy issue were high (>60%) across all groups. Drug overdose prevention may be an issue that is more politically feasible to inspire action than other, more polarized health policy issues. However, despite bipartisan consensus on the importance of this issue, there may be less consensus on the specific policy solutions (eg, greater investment in treatment and harm reduction–oriented solutions vs more focus on supply reduction through law enforcement efforts) that would achieve broad support and be most effective at addressing the crisis. 39

The impact of the overdose crisis has not been distributed evenly across the US population. Indicators of greater economic vulnerability, including Medicaid enrollment and increased financial strain over the past year, were associated with greater likelihood of experiencing a personal overdose loss. Certain geographic regions, such as New England and nonmetropolitan areas, were disproportionately affected as well. These patterns align with data on the individual- and area-level characteristics of individuals who died of drug overdose on some dimensions, notably economic vulnerability 40 and geographic heterogeneity. 41 However, they vary in other ways from more recent surveillance data, as the overdose crisis has evolved rapidly over time. For example, while our data showed that White respondents were more likely to report knowing someone who died of a drug overdose, drug overdose mortality rates have accelerated in recent years among non-Hispanic Black populations and are significantly elevated among American Indian and Alaska Native individuals, 40 , 42 an important group that we were unable to identify in sufficient numbers in this study.

Despite the aforementioned patterns, findings from this study also showed that no community or sociodemographic group in the US had not experienced personal overdose loss. Although personal overdose loss was reported more frequently among groups with lower income, it was still a common experience in groups of all economic strata, including among 26.0% of persons with annual household income over $100 000. That this is a common, shared experience among sociodemographic groups in the US population may help to reduce stigma regarding overdose death, unite otherwise disconnected groups, and mobilize leaders to advance policy solutions.

The findings should be considered in the context of the study’s limitations. First, personal overdose loss may be underreported due to the stigma of overdose. One way in which this may occur is when respondents are unaware of the cause of death due to lack of disclosure by next-of-kin. A second limitation is that we did not ask respondents about the recency of their personal overdose loss(es). This may explain why some patterns in the experience of personal overdose loss diverged from the most recent national data on individuals who died of drug overdose, notably racial and ethnic inequalities. 40 , 42 Understanding the impact of personal overdose loss among American Indian and Alaska Native individuals is of particular importance given the disproportionate burden of the overdose crisis in this population 42 ; future survey-based research should oversample among this population to ensure a sufficient sample to generate representative estimates.

This cross-sectional study found that 32% of US adults, or 82.7 million, had someone they know die of a drug overdose, and most of this group had experienced the death of a relative or close friend. This experience extended across the political spectrum, offering a potential avenue for increasing the mobilization of this group and the political feasibility of needed policy action to decrease overdose deaths.

Accepted for Publication: April 9, 2024.

Published: May 31, 2024. doi:10.1001/jamahealthforum.2024.1262

Corresponding Author: Alene Kennedy-Hendricks, PhD, Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, 624 N Broadway, Hampton House 408, Baltimore, MD 21205 ( [email protected] ).

Author Contributions: Drs Kennedy-Hendricks and Ettman had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kennedy-Hendricks, Ettman, Gollust, Bandara, Galea.

Acquisition, analysis, or interpretation of data: Kennedy-Hendricks, Ettman, Gollust, Abdalla, Castrucci, Galea.

Drafting of the manuscript: Kennedy-Hendricks, Ettman.

Critical review of the manuscript for important intellectual content: Ettman, Gollust, Bandara, Abdalla, Castrucci, Galea.

Statistical analysis: Kennedy-Hendricks.

Obtained funding: Ettman, Abdalla, Galea.

Administrative, technical, or material support: Abdalla, Galea.

Supervision: Ettman, Castrucci, Galea.

Conflict of Interest Disclosures: Dr Ettman reported receiving grants from the de Beaumont Foundation during the conduct of the study. Dr Gollust reported receiving grants from the National Institutes of Health and the Robert Wood Johnson Foundation outside the submitted work. Dr Galea reported receiving grants from the de Beaumont Foundation and serving on the board of Sharecare. No other disclosures were reported.

Funding/Support: The COVID-19 and Life Stressors Impact on Mental Health and Well-Being (CLIMB) study wave 4 was funded by a grant from the de Beaumont Foundation.

Role of the Funder/Sponsor: Members from the de Beaumont Foundation provided feedback on the CLIMB questionnaire and had a role in the design and conduct of the study and preparation, review, and approval of the manuscript. The de Beaumont Foundation did not have a role in the collection, management, analysis, and interpretation of the data and the decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 2 .

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Understanding the Opioid Overdose Epidemic

What to know.

The number of opioid-related deaths has been rising continuously since 1999.
Three distinct waves of increases are related to different types of opioids throughout the last 25 years.
Increasing communities' support, capacity, and education may help turn the tide and prevent overdose deaths.

Opioid-related deaths are rising

Drug overdose deaths.

The number of people who died from a drug overdose in 2021 was over six times the number in 1999.
The number of drug overdose deaths did not significantly change from 2021 to 2022.
Over 75% of the nearly 107,000 drug overdose deaths in 2022 involved an opioid.
Opioid-involved death rates decreased by 12.5%.
Prescription opioid-involved death rates remained the same.
Heroin-involved death rates decreased nearly 36%.
Synthetic opioid-involved death rates (excluding methadone) increased over 4%. 1

Three waves of opioid overdose deaths

Line infographic showing 3 waves of opioid overdose deaths from 1999-2021.

From 1999-2021, nearly 645,000 people died from an overdose involving any opioid, including prescription and illicit opioids. 2

This rise in opioid overdose deaths can be outlined in three distinct waves.

The first wave began with increased prescribing of opioids in the 1990s, with overdose deaths involving prescription opioids (natural and semi-synthetic opioids and methadone) increasing since at least 1999. 3

Second wave

The second wave began in 2010, with rapid increases in overdose deaths involving heroin . 4

The third wave began in 2013, with significant increases in overdose deaths involving synthetic opioids, particularly those involving illegally made fentanyl . 5 6 7 The market for illegally made fentanyl continues to change, and it can be found in combination with heroin, counterfeit pills, and cocaine. 8

Many opioid-involved overdose deaths also include other drugs . 9 10

Confronting the opioid overdose epidemic

CDC is committed to fighting the opioid overdose epidemic and supporting states and communities as they continue work to identify outbreaks, collect data, respond to overdoses, and provide care to those in their communities.

224 people died each day from an opioid overdose in 2022.

What CDC's work focuses on

Monitoring trends to better understand and respond to the epidemic.
Advancing research by collecting and analyzing data on opioid-related overdoses and improving data quality to better identify areas that need assistance and to evaluate prevention efforts.
Building state, local and tribal capacity by equipping states with resources, improving data collection, and supporting use of evidence-based strategies. Overdose Data to Action (OD2A) is cooperative agreement provides funding to 90 health departments under two distinct OD2A programs to reduce drug overdoses and the impact of related harms.
Supporting providers, healthcare systems, and payers with data, tools, and guidance for evidence-based decision-making to improve opioid prescribing and patient safety.
Partnering with public safety officials and community organizations , including law enforcement, to address the growing illicit opioid problem.
Increasing public awareness about prescription opioid misuse and overdose and to make safe choices about opioids.

Overdose Data to Action

Overdose Data to Action (OD2A) is a cooperative agreement that provides funding to 90 health departments under two distinct OD2A programs ( State and Local ) to reduce drug overdoses and the impact of related harms. This cooperative agreement supports jurisdictions in implementing prevention activities and in collecting accurate, comprehensive, and timely data on nonfatal and fatal overdoses and in using those data to enhance programmatic and surveillance efforts. OD2A focuses on understanding and tracking the complex and changing nature of the drug overdose crisis by seamlessly integrating data and prevention strategies.

Collaboration helps save lives

Collaboration is essential for success in preventing opioid overdose deaths. Medical personnel, emergency departments, first responders, public safety officials, mental health and substance use treatment providers, community-based organizations, public health, and members of the community all bring awareness, resources, and expertise to address this complex and fast-moving epidemic. Together, we can better coordinate efforts to prevent opioid overdoses and deaths.

Additional resources

HHS.gov: About the Opioid Epidemic

SAMHSA’s Behavioral Health Treatment Services Locator

Drug Overdose Deaths in the United States, 2002–2022

Trends and Geographic Patterns in Drug and Synthetic Opioid Overdose Deaths 2013–2019 — United States (MMWR)

People looking over data charts and graphics.

About Overdose Prevention

Spencer MR, Garnett MF, Miniño AM. Drug Overdose Deaths in the United Sates, 2002-2022 . NCHS Data Brief, no 491. Hyattsville, MD: National Center for Health Statistics. 2024.
Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National Center for Health Statistics; 2021. Available at http://wonder.cdc.gov .
Centers for Disease Control and Prevention (CDC). Vital signs: overdoses of prescription opioid pain relievers—United States, 1999–2008. MMWR MorbMortal Wkly Rep. 2011 Nov 4; 60(43):1487-1492.
Rudd RA, Paulozzi LJ, Bauer MJ, Burleson RW, Carlson RE, Dao D, Davis JW, Dudek J, Eichler BA, Fernandes JC, Fondario A. Increases in heroin overdose deaths—28 states, 2010 to 2012. MMWR MorbMortal Wkly Rep. 2014 Oct 3; 63(39):849.
Gladden RM, Martinez P, Seth P. Fentanyl law enforcement submissions and increases in synthetic opioid-involved overdose deaths—27 states, 2013–2014. MMWR MorbMortal Wkly Rep. 2016; 65:837–43.
O'Donnell JK, Gladden RM, Seth P. Trends in deaths involving heroin and synthetic opioids excluding methadone, and law enforcement drug product reports, by census region—United States, 2006–2015. MMWR MorbMortal Wkly Rep. 2017; 66:897–903.
O'Donnell JK, Halpin J, Mattson CL, Goldberger BA, Gladden RM. Deaths involving fentanyl, fentanyl analogs, and U-47700—10 states, July–December 2016. MMWR Morb Mortal Wkly Rep. 2017; 66:1197–202.
Drug Enforcement Administration. 2019 National Drug Threat Assessment . Drug Enforcement Administration Strategic Intelligence Section, U.S. Department of Justice. Published December 2019. Accessed March 17, 2020.
Gladden M, O'Donnell J, Mattson C, Seth P. Changes in Opioid-Involved Overdose Deaths by Opioid Type and Presence of Benzodiazepines, Cocaine, and Methamphetamine – 25 States, July-December 2017 to January-June 2018 . MMWR Morb Mortal Wkly Rep 2019:68(34);737-744.
Kariisa M, Scholl L, Wilson N, Seth P, Hoots B. Drug Overdose Deaths involving Cocaine and Psychostimulants with Abuse Potential – United States, 2003-2017 . MMWR Morb Mortal Wkly Rep 2019:68(17);41-43.
Mattson CL, Tanz LJ, Quinn K, Kariisa M, Patel P, Davis NL. Trends and Geographic Patterns in Drug and Synthetic Opioid Overdose Deaths — United States, 2013–2019. MMWR Morb Mortal Wkly Rep 2021;70:202–207. DOI: http://dx.doi.org/10.15585/mmwr.mm7006a4 .
Hedegaard H, Miniño AM, Spencer MR, Warner M. Drug Overdose Deaths in the United States, 1999–2020 . National Center for Health Statistics, December 2021.
Spencer MR, Miniño AM, Warner M. Drug overdose deaths in the United States, 2001–2021. NCHS Data Brief, no 457. Hyattsville, MD: National Center for Health Statistics. 2022. DOI: https://dx.doi.org/10.15620/cdc:122556

Overdose Prevention

Overdose prevention is a CDC priority that impacts families and communities. Drug overdose is a leading cause of preventable death in the U.S.

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The Effects of Drug Addiction on the Brain and Body

Signs of drug addiction, effects of drug addiction.

Drug addiction is a treatable, chronic medical disease that involves complex interactions between a person’s environment, brain circuits, genetics, and life experiences.

People with drug addictions continue to use drugs compulsively, despite the negative effects.

Substance abuse has many potential consequences, including overdose and death. Learn about the effects of drug addiction on the mind and body and treatment options that can help.

Verywell / Theresa Chiechi

Drug Abuse vs. Drug Addiction

While the terms “drug abuse” and “drug addiction” are often used interchangeably, they're different. Someone who abuses drugs uses a substance too much, too frequently, or in otherwise unhealthy ways. However, they ultimately have control over their substance use.

Someone with a drug addiction uses drugs in a way that affects many parts of their life and causes major disruptions. They continue to use drugs compulsively despite the negative consequences.

The signs of drug abuse and addiction include changes in behavior, personality, and physical appearance. If you’re concerned about a loved one’s substance use, here are some of the red flags to watch out for:

Changes in school or work performance
Secretiveness
Relationship problems
Risk-taking behavior
Legal problems
Aggression
Mood swings
Changes in hobbies or friends
Sudden weight loss or gain
Unexplained odors on the body or clothing

Drug Addiction in Men and Women

Men and women are equally likely to develop drug addictions. However, men are more likely than women to use illicit drugs, die from a drug overdose, and visit an emergency room for addiction-related health reasons. Women are more susceptible to intense cravings and repeated relapses.

People can become addicted to any psychoactive ("mind-altering") substance. Common addictive substances include alcohol , tobacco ( nicotine ), stimulants, hallucinogens, and opioids .

Many of the effects of drug addiction are similar, no matter what substance someone uses. The following are some of the most common effects of drug addiction.

Effects of Drug Addiction on the Body

Drug addiction can lead to a variety of physical consequences ranging in seriousness from drowsiness to organ damage and death:

Shallow breathing
Elevated body temperature
Rapid heart rate
Increased blood pressure
Impaired coordination and slurred speech
Decreased or increased appetite
Tooth decay
Skin damage
Sexual dysfunction
Infertility
Kidney damage
Liver damage and cirrhosis
Various forms of cancer
Cardiovascular problems
Lung problems
Overdose and death

If left untreated drug addiction can lead to serious, life-altering effects on the body.

Dependence and withdrawal also affect the body:

Physical dependence : Refers to the reliance on a substance to function day to day. People can become physically dependent on a substance fairly quickly. Dependence does not always mean someone is addicted, but the longer someone uses drugs, the more likely their dependency is to become an addiction.
Withdrawal : When someone with a dependence stops using a drug, they can experience withdrawal symptoms like excessive sweating, tremors, panic, difficulty breathing, fatigue , irritability, and flu-like symptoms.

Overdose Deaths in the United States

According to the Centers for Disease Control and Prevention (CDC), over 100,000 people in the U.S. died from a drug overdose in 2021.

Effects of Drug Addiction on the Brain

All basic functions in the body are regulated by the brain. But, more than that, your brain is who you are. It controls how you interpret and respond to life experiences and the ways you behave as a result of undergoing those experiences.

Drugs alter important areas of the brain. When someone continues to use drugs, their health can deteriorate both psychologically and neurologically.

Some of the most common mental effects of drug addiction are:

Cognitive decline
Memory loss
Mood changes and paranoia
Poor self/impulse control
Disruption to areas of the brain controlling basic functions (heart rate, breathing, sleep, etc.)

Effects of Drug Addiction on Behavior

Psychoactive substances affect the parts of the brain that involve reward, pleasure, and risk. They produce a sense of euphoria and well-being by flooding the brain with dopamine .

This leads people to compulsively use drugs in search of another euphoric “high.” The consequences of these neurological changes can be either temporary or permanent.

Difficulty concentrating
Irritability
Angry outbursts
Lack of inhibition
Decreased pleasure/enjoyment in daily life (e.g., eating, socializing, and sex)
Hallucinations

Help Someone With Drug Addiction

If you suspect that a loved one is experiencing drug addiction, address your concerns honestly, non-confrontationally, and without judgment. Focus on building trust and maintaining an open line of communication while setting healthy boundaries to keep yourself and others safe. If you need help, contact the SAMHSA National Helpline at 1-800-662-4357.

Effects of Drug Addiction on an Unborn Child

Drug addiction during pregnancy can cause serious negative outcomes for both mother and child, including:

Preterm birth
Maternal mortality

Drug addiction during pregnancy can lead to neonatal abstinence syndrome (NAS) . Essentially, the baby goes into withdrawal after birth. Symptoms of NAS differ depending on which drug has been used but can include:

Excessive crying
Sleeping and feeding issues

Children exposed to drugs before birth may go on to develop issues with behavior, attention, and thinking. It's unclear whether prenatal drug exposure continues to affect behavior and the brain beyond adolescence.

While there is no single “cure” for drug addiction, there are ways to treat it. Treatment can help you control your addiction and stay drug-free. The primary methods of treating drug addiction include:

Psychotherapy : Psychotherapy, such as cognitive behavioral therapy (CBT) or family therapy , can help someone with a drug addiction develop healthier ways of thinking and behaving.
Behavioral therapy : Common behavioral therapies for drug addiction include motivational enhancement therapy (MET) and contingency management (CM). These therapy approaches build coping skills and provide positive reinforcement.
Medication : Certain prescribed medications help to ease withdrawal symptoms. Some examples are naltrexone (for alcohol), bupropion (for nicotine), and methadone (for opioids).
Hospitalization : Some people with drug addiction might need to be hospitalized to detox from a substance before beginning long-term treatment.
Support groups : Peer support and self-help groups, such as 12-step programs like Alcoholics Anonymous, can help people with drug addictions find support, resources, and accountability.

A combination of medication and behavioral therapy has been found to have the highest success rates in preventing relapse and promoting recovery. Forming an individualized treatment plan with your healthcare provider's help is likely to be the most effective approach.

Drug addiction is a complex, chronic medical disease that results in compulsive use of psychoactive substances despite the negative consequences.

Some effects of drug abuse and addiction include changes in appetite, mood, and sleep patterns. More serious health issues such as cognitive decline, major organ damage, overdose, and death are also risks. Addiction to drugs while pregnant can lead to serious outcomes for both mother and child.

Treatment for drug addiction may involve psychotherapy , medication, hospitalization, support groups, or a combination.

If you or someone you know is experiencing substance abuse or addiction, contact the Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at 1-800-662-4357.

American Society of Addiction Medicine. Definition of addiction .

HelpGuide.org. Drug Abuse and Addiction .

Tennessee Department of Mental Health & Substance Abuse Services. Warning signs of drug abuse .

National Institute on Drug Abuse. Sex and gender differences in substance use .

Cleveland Clinic. Drug addiction .

National Institute on Drug Abuse. Drugs, Brains, and Behavior: The Science of Addiction Drugs and the Brain .

American Heart Association. Illegal Drugs and Heart Disease .

American Addiction Centers. Get the facts on substance abuse .

Szalavitz M, Rigg KK, Wakeman SE. Drug dependence is not addiction-and it matters . Ann Med . 2021;53(1):1989-1992. doi:10.1080/07853890.2021.1995623

Centers for Disease Control and Prevention. Drug overdose deaths in the U.S. top 100,000 annually .

American Psychological Association. Cognition is central to drug addiction .

National Institute on Drug Abuse. Understanding Drug Use and Addiction DrugFacts .

MedlinePlus. Neonatal abstinence syndrome .

National Institute on Drug Abuse. Treatment and recovery .

Grella CE, Stein JA. Remission from substance dependence: differences between individuals in a general population longitudinal survey who do and do not seek help . Drug and Alcohol Dependence. 2013;133(1):146-153. doi:10.1016/j.drugalcdep.2013.05.019

By Laura Dorwart Dr. Dorwart has a Ph.D. from UC San Diego and is a health journalist interested in mental health, pregnancy, and disability rights.

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Opioid overdose

The term “opioids” includes compounds that are extracted from the poppy plant (Papaver somniferum) as well as semisynthetic and synthetic compounds with similar properties that can interact with opioid receptors in the brain.
Opioids are commonly used for the treatment of pain, and include medicines such as morphine, fentanyl and tramadol.
Their non-medical use, prolonged use, misuse and use without medical supervision can lead to opioid dependence and other health problems.
Due to their pharmacological effects, opioids can cause breathing difficulties, and opioid overdose can lead to death.
Worldwide, in 2019 about 600 000 deaths were attributable to drug use. Close to 80% of these deaths are related to opioids, with about 25% of those deaths caused by opioid overdose.
There are effective treatment interventions for opioid dependence that can decrease the risk of overdose, yet less than 10% of people who need such treatment are receiving it.
The medication naloxone can prevent death from an opioid overdose if administered in time.

The term “opioids” includes compounds that are extracted from the poppy plant ( Papaver somniferum ) as well as semisynthetic and synthetic compounds with similar properties that can interact with opioid receptors in the brain. Opioids have analgesic and sedative effects, and such medicines as morphine, codeine and fentanyl are commonly used for the management of pain. Opioid medicines methadone and buprenorphine are used for maintenance treatment of opioid dependence. After intake, opioids can cause euphoria, which is one of the main reasons why they are taken for non-medical reasons. Opioids include heroin, morphine, codeine, fentanyl, methadone, tramadol, and other similar substances. Due to their pharmacological effects, they can cause difficulties with breathing, and opioid overdose can lead to death.

Their regular non-medical use, prolonged use, misuse and use without medical supervision can lead to opioid dependence and other health problems. Opioid dependence is a disorder of regulation of opioid use arising from repeated or continuous use of opioids. The characteristic feature of dependence is a strong internal drive to use opioids, which manifests itself by impaired ability to control use, increasing priority given to use over other activities and persistence of use despite harm or negative consequences. Physiological features of dependence may also be present, including increased tolerance to the effects of opioids, withdrawal symptoms following cessation or reduction in use, or repeated use of opioids or pharmacologically similar substances to prevent or alleviate withdrawal symptoms (1) .

Worldwide, about 296 million people (or 5.8% of the global population aged 15–64 years) used drugs at least once in 2021. Among them, about 60 million people used opioids. About 39.5 million people lived with drug use disorders in 2021 (2) . Most people dependent on opioids used illicitly cultivated and manufactured heroin, but the proportion of those using prescription opioids is growing.

Opioid use can lead to death due to the effects of opioids on the part of the brain which regulates breathing. An opioid overdose can be identified by a combination of three signs and symptoms:

pinpoint pupils
unconsciousness
difficulties with breathing.

Worldwide, about 600 000 deaths were attributable to drug use in 2019. Close to 80% of these deaths are related to opioids, with about 25% of those deaths caused by opioid overdose. According to WHO estimates, approximately 125 000 people died of opioid overdose in 2019. Opioid overdoses that do not lead to death are several times more common than fatal overdoses.

The number of opioid overdoses has increased in recent years in several countries, in part due to the increased availability of opioids used in the management of chronic pain, and also due to increasing use of highly potent opioids appearing on the illicit drug market. In the United States of America (USA) the number of people dying from drug overdose amounted to 70 630 in 2019, and approximately half of these deaths involved synthetic opioids. From 2013 to 2019, the age-adjusted synthetic opioid death rates in the United States increased by 1040% (3) . During the COVID-19 pandemic, a further substantial increase in drug overdose deaths was reported in the USA, primarily driven by rapid increases in overdose deaths involving synthetic opioids (4) .

Fentanyl is a potent synthetic opioid that is used as a pain reliever and as an anaesthetic. It is approximately 50–100 times more potent than morphine. Fentanyl in various formulations is on the WHO Model List of Essential Medicines. However, fentanyl and its chemically-similar analogues (including carfentanil, acetylfentanyl, butyrfentanyl, and furanyl fentanyl) have been associated with a spike in deaths from opioid overdose. There is evidence that drug dealers may be adding fentanyl to increase the potency of their products (such as heroin) and selling fentanyl as counterfeit tablets, created to look like authentic prescription medications. Therefore, many users who test positive for fentanyl and its analogues do not realize that they took the substance.

Risk factors for opioid overdose

There are a number of risk factors for opioid overdose. These include:

having an opioid use disorder;
taking opioids by injection;
resumption of opioid use after an extended period of abstinence (e.g. following detoxification, release from incarceration, cessation of treatment);
using prescription opioids without medical supervision;
high prescribed dosage of opioids (more than 100 mg of morphine or equivalent daily).
using opioids in combination with alcohol and/or other substances or medicines that suppress respiratory function such as benzodiazepines, barbiturates, anesthetics or some pain medications; and
having concurrent medical conditions such as HIV, liver or lung diseases or mental health conditions.

Males, people of older age and people with low socio-economic status are at higher risk of opioid overdose than women, people of young age groups and people with higher socio-economic status.

Emergency responses to opioid overdose

Death following opioid overdose is preventable if the person receives basic life support and the timely administration of the drug naloxone. Naloxone is an antidote to opioids that will reverse the effects of an opioid overdose if administered in time. Naloxone has virtually no effect in people who have not taken opioids.

Access to naloxone is generally limited to health professionals. In many countries there is still limited availability of naloxone even in medical settings, including in ambulances. On the other hand, some countries have already made naloxone available in pharmacies without prescription. Several countries (Australia, Canada, Italy, the United Kingdom of Great Britain and Northern Ireland and Ukraine) have introduced naloxone as over-the-counter medication and have also started proactive dissemination in communities.

In recent years, a number of programmes around the world have shown that providing naloxone to people likely to witness an opioid overdose, in combination with training on the use of naloxone and on the resuscitation of people following an opioid overdose, could substantially reduce the number of deaths resulting from opioid overdose. This is particularly relevant for people with opioid use disorders and leaving prison, as they have very high rates of opioid overdose during the first four weeks after release.

People most likely to witness an opioid overdose

People who are most likely to witness an opioid overdose are:

people at risk of an opioid overdose themselves;
friends and families of people who use opioids on a regular basis; and
health-care workers, the emergency services, people providing accommodation to people who use opioids, and peer education and outreach workers as well as others whose work brings them into contact with people who are at risk of overdose.

Prevention of opioid overdose

Beyond approaches to reducing drug use in general in the community, there are specific measures to prevent opioid overdose. These include:

increasing the availability of opioid dependence treatment, including for those dependent on prescription opioids;
reducing and preventing irrational or inappropriate opioid prescribing;
monitoring opioid prescribing and dispensing; and
limiting inappropriate over-the-counter sales of opioids.

The gap between recommendations and practice is significant. Only half of countries provide access to effective treatment options for opioid dependence and less than 10% of people worldwide in need of such treatment are receiving it (5) .

WHO response and recommendations

WHO supports countries in their efforts to ensure rational use of opioids and their optimal availability for medical purposes and minimization of their misuse and non-medical use. Following the recommendation of WHO’s Expert Committee on Drug Dependence (6) , a number of synthetic opioids, including fentanyl analogues, have been placed under international control, which means rigorous regulation for their availability.

WHO continues to monitor several fentanyl analogues through its surveillance system for new psychoactive substances, alerting countries to the potential dangers associated with these substances. Collection of such data is important as information about the patterns of use, misuse and non-medical use of opioids is very limited.

WHO also supports countries in monitoring trends in drug use and related harm, to better understand the scale of opioid dependence and opioid overdose.

WHO recommends that naloxone be made available to people likely to witness an opioid overdose, as well as training in the management of opioid overdose. In suspected opioid overdose, first responders should focus on airway management, assisting ventilation and administering naloxone. After successful resuscitation following the administration of naloxone, the level of consciousness and breathing of the affected person should be closely observed until full recovery has been achieved.

WHO recommends the use of a range of treatment options for opioid dependence. These include opioid agonist maintenance treatment (with medicines such as methadone and buprenorphine), which has the strongest evidence of effectiveness and cost-effectiveness, as well as psychosocial treatment and support, and pharmacological treatment with opioid antagonists (such as naltrexone). WHO supports countries in improving the coverage and quality of treatment programmes for opioid dependence and introducing them where they do not already exist.

WHO also issues normative guidance to promote the appropriate use of opioids for pain and palliative care. Appropriate use and regulation of opioid analgesics ensures that they are available where needed whilst preventing their diversion and harm related to misuse.

In 2016, under the framework of the WHO/UNODC Programme on Drug Dependence Treatment and Care, the “Stop Overdose Safely (S-O-S)” Initiative was launched, to provide training on recognizing the risk of overdose and providing emergency care in the event of an overdose. As part of this Initiative, a multi-site study on community management of opioid overdose was implemented in Kazakhstan, Kyrgyzstan, Tajikistan, and Ukraine in 2019-2020. About 40 000 kits of naloxone were distributed, more than 14 000 people were trained as part of the project and around 90% of those participants who witnessed an overdose reported using naloxone. In almost all instances, it was recorded that the person with overdose survived. Evaluation of the project showed that it was widely accepted by stakeholders, ranging from people who use drugs through to health and law enforcement officials ( 7) .

WHO (2019). International Classification of Diseases for Mortality and Morbidity Statistics. Eleventh Revision.

UNODC (2023). World Drug Report 2023. Available at: https://www.unodc.org/unodc/en/data-and-analysis/world-drug-report-2023.html

Trends and Geographic Patterns and Synthetic Opioid Overdose Deaths – United States, 2013-2019. Morbidity and Mortality Weekly Report, Vol. 70, No 6. Available at: https://www.cdc.gov/mmwr/volumes/70/wr/mm7006a4.htm?s_cid=mm7006a4_w

CDC Emergency Preparedness and Response: Increase in Fatal Drug Overdoses Across the United States Driven by Synthetic Opioids Before and During the COVID-19 Pandemic, 17 December 2020. Available at: https://emergency.cdc.gov/han/2020/han00438.asp

Degenhardt L, Glantz M, Evans-Lacko S, et al. (2017). Estimating treatment coverage for people with substance use disorders: an analysis of data from the World Mental Health Surveys. World Psychiatry. 2017;16(3):299-307. doi:10.1002/wps.2045

WHO Expert Committee on Drug Dependence: forty-third report (WHO Technical Report Series, No. 1034). WHO, 2021. Available at: https://www.who.int/publications/i/item/9789240023024

UNODC-WHO Stop-Overdose-Safely (S-O-S) project implementation in Kazakhstan, Kyrgyzstan, Tajikistan and Ukraine: summary report. WHO and UNODC, 2021. Available at: https://apps.who.int/iris/handle/10665/340497

UNODC-WHO Stop-Overdose-Safely (‎S-O-S)‎ project implementation in Kazakhstan, Kyrgyzstan, Tajikistan and Ukraine: summary report

WHO-UNODC Stop Overdose Safely (S-O-S) initiative

WHO Guidelines “Community management of opioid overdose”

The public health dimension of the world drug problem: how WHO works to prevent drug misuse, reduce harm and improve safe access to medicine

International Standards for the Treatment of Drug Use Disorders

WHO Technical Report Series 1018

Drugs (psychoactive)

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Opioid Overdose

What is opioid overdose.

Substance use disorders (SUDs) impact the lives of millions of Americans. More than 100,000 people died from drug overdoses from April 2020 to 2021, an increase of 28.5% from the prior year, according to a report by the Centers for Disease Control and Prevention (CDC) .

An opioid overdose can occur when a person:

Overdoses on an illicit opioid drug, such as heroin or morphine
Overdoses on methadone
Accidentally takes an extra dose
Deliberately misuses a prescription opioid or opioid-based pain medication in way that was not as prescribed by their physician
Mixes opioids with other prescriptions, alcohol, or over-the-counter medications. Overdoses can be fatal when mixing an opioid with anxiety treatment medications or derivatives of Benzodiazepine, such as Xanax or valium.
Uses medication prescribed for someone else. Children are particularly vulnerable to accidental overdoses if they take medication not intended for them.

How to Prevent Opioid Overdose

Opioid overdose can occur even with prescription opioid pain relievers and medications used in treating SUD such as methadone and buprenorphine . In addition, individuals using naltrexone for MOUD have a reduced tolerance to opioids, and therefore, using the same, or even lower doses of opioids used in the past, can cause life-threating consequences.

Always follow the instructions you receive with your medication. Ask your practitioner or pharmacist if you have questions or are unsure of how to take your medication.

The following tips can help you or a loved one avoid opioid overdose:

Take medicine as prescribed by your practitioner
Do not take more medication or take it more often than instructed
Never mix pain medicines with alcohol, sleeping pills, or illicit substances
Never take anyone else medication
Prevent children and pets from accidental ingestion by storing your medication out or reach. For more information, visit CDC’s Up and Away educational campaign.
Dispose of unused medication safely. Talk to your MOUD practitioner for guidance, or for more information on the safe disposal of unused medications, visit FDA's disposal of unused medicines or DEA's drug disposal webpages .

How to Recognize Opioid Overdose

Opioid overdose is life-threatening and requires immediate emergency attention. Recognizing the signs of opioid overdose is essential to saving lives.

Call 911 immediately if a person exhibits ANY of the following symptoms:

Their face is extremely pale and/or feels clammy to the touch
Their body goes limp
Their fingernails or lips have a purple or blue color
They start vomiting or making gurgling noises
They cannot be awakened or are unable to speak
Their breathing or heartbeat slows or stops

How to Treat Opioid Overdose

Family members, caregivers, or the people who spend time with individuals using opioids need to know how to recognize the signs of an overdose and how to administer life-saving services until emergency medical help arrives. Individuals experiencing an opioid overdose will not be able to treat themselves. Naloxone was approved by the Food and Drug Administration (FDA) as the first over the counter medication to prevent opioid overdose. Check with your healthcare provider, pharmacy, community-based distribution programs, local public health organizations or the local health departments on how to obtain naloxone in your state.

If you suspect someone is experiencing an opioid overdose, take action immediately:

Begin CPR if the person has stopped breathing or if breathing is very weak (best performed by someone who has training)
Treat the person with naloxone or nalmefene to reverse opioid overdose (if available)

Publications and Resources

SAMHSA's Overdose Prevention and Response Toolkit
Opioid Overdose and Naloxone Manual at Harm Reduction Coalition
Opioid Overdose Prevention at the New York State Department of Health Prescribe to Prevent: Prescribe Naloxone, Save a Life
Homelessness Programs and Resources

Opioid Treatment Program Directory

Find treatment programs in your state that treat addiction and dependence on opioids.

If you, or someone you know, need help to stop using substances – whether the problem is methamphetamine, alcohol or another drug – call SAMHSA’s National Helpline at 1-800-662-HELP (4357) or TTY: 1-800-487-4889
FindTreatment.gov – this locator provides information on state-licensed providers who specialize in treating substance use disorders and mental illness.
Buprenorphine Practitioner Locator - Find practitioners authorized to treat opioid dependency with buprenorphine by state.

Buprenorphine

Buprenorphine is a medication approved by the Food and Drug Administration (FDA) to treat Opioid Use Disorder (OUD).

Methadone is a medication used to treat Opioid Use Disorder (OUD). Methadone is a long-acting full opioid agonist, and a schedule II controlled medication.

Naltrexone is a medication approved by the Food and Drug Administration (FDA) to treat both alcohol use disorder (AUD) and opioid use disorder (OUD).

Contact Information

Opioid Treatment Program Contacts For information about Medications for Opioid Use Disorder (MOUD) or the certification of opioid treatment programs (OTPs), contact the SAMHSA Division of Pharmacologic Therapies at 240-276-2700 or [email protected] . For assistance with the Opioid Treatment Program Extranet, contact the OTP helpdesk at 1-866-348-5741 or [email protected] .

Provider Support Contacts For general information, providers can contact SAMHSA's Center for Substance Abuse Treatment (CSAT) at 1-866-287-2728 or email [email protected] .

The New York Times

The upshot | short answers to hard questions about the opioid crisis.

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Short Answers to Hard Questions About the Opioid Crisis

By JOSH KATZ UPDATED August 10, 2017

On Thursday, President Trump said he intended to declare the opioid crisis a national emergency , as previously recommended by his opioid commission.

With the death toll from drugs rising faster than ever , you might feel that you could use a little catching up. For a quick refresher, and more on the practical effects of a formal declaration of an emergency, here are answers to 12 critical questions.

How bad is it?

Drug overdoses are the leading cause of death for Americans under 50, and deaths are rising faster than ever, primarily because of opioids.

Overdoses killed more people last year than guns or car accidents, and are doing so at a pace faster than the H.I.V. epidemic at its peak. In 2015, roughly 2 percent of deaths — one in 50 — in the United States were drug-related.

Percentage of deaths classified as drug-related

Overdoses are merely the most visible and easily counted symptom of the problem. Over two million Americans are estimated to have a problem with opioids . According to the latest survey data , over 97 million people took prescription painkillers in 2015; of these, 12 million did so without being directed by a doctor.

What is an “opioid”?

That’s not really a helpful answer.

The first such drug, and the one from which the opioid receptors get their name, was opium. Opium, a narcotic obtained from a kind of poppy, has been used in human societies for thousands of years. From opium people derived a whole host of other drugs with similar properties: first morphine, then heroin, then prescription painkillers like Vicodin, Percocet and OxyContin. Opium along with all of these derivatives are collectively known as opiates .

Then there are a handful of compounds that act just like opiates but aren’t made from the plant. Opiates along with these synthetic drugs — chiefly methadone and fentanyl — are grouped together into the category of substances called opioids .

Opioid receptors regulate pain and the reward system in the human body. That makes opioids powerful painkillers, but also debilitatingly addictive.

So is this crisis about prescription painkillers or heroin?

The crisis has its roots in the overprescription of opioid painkillers, but since 2011 overdose deaths from prescription opioids have leveled off. Deaths from heroin and fentanyl, on the other hand, are rising fast. In several states where the drug crisis is particularly severe, including Rhode Island , Pennsylvania and Massachusetts , fentanyl is now involved in over half of all overdose fatalities.

Drug overdose deaths involving ...

While heroin and fentanyl are the primary killers now, experts agree that the epidemic will not stop without halting the flow of prescription opioids that got people hooked in the first place.

Show me one way the epidemic has changed.

The latest iteration of the opioid epidemic has been especially deadly among adults in their 20s and early 30s.

Distribution of drug deaths by age

In 2000, the most common age for drug deaths, including those not involving opioids, was around 40. This was the generation that first grew addicted to prescription opioids in large numbers — white people especially so. Now there’s evidence that the opioid epidemic is dividing into two waves, with a new group of younger drug users growing addicted to, and dying from, heroin or fentanyl rather than prescription pills.

Where is the worst of the problem?

There’s a lot of geographic variation in the rate of drug deaths, with the highest overdose rates clustered in Appalachia, the Rust Belt and New England.

Teasing out the reasons for the geographical differences is not easy. In certain places, the ways in which people use drugs could be more dangerous (you’re more likely to die from injecting heroin than you are from smoking it, for example).

But it’s clear that a significant portion of the variation in deaths, if not necessarily in use, is being driven by the appearance of fentanyl in the drug supply. Fentanyl, a highly potent opioid, affects heroin users and pill users both, the latter often falling victim to counterfeit pills that look like prescription painkillers.

So far, the white population has been hardest hit, but this is beginning to change. Several critics have been quick to point out that the country’s response was not nearly as public-health-oriented during the crack cocaine epidemic in the 1980s, which disproportionately affected African-Americans.

Why has this problem gotten so much worse in recent years?

Addiction to opioids goes back centuries, but the current crisis really starts in the 1980s. A handful of highly influential journal articles relaxed long-standing fears among doctors about prescribing opioids for chronic pain. The pharmaceutical industry took note, and in the mid-1990s began aggressively marketing drugs like OxyContin. This aggressive and at times fraudulent marketing, combined with a new focus on patient satisfaction and the elimination of pain, sharply increased the availability of pharmaceutical narcotics.

Pill mills began popping up around the country as communities were flooded with prescription opioids. Over the next decade, a growing number of people grew addicted to the drugs, whether from prescriptions or from taking them recreationally. For many, what started with pills evolved into a heroin addiction.

At the same time, the heroin market was changing. The price plummeted. Newly decentralized drug distribution networks pushed heroin and counterfeit pharmaceuticals into suburban and rural areas where they had never been. Everywhere the suppliers went, they found a ready and willing customer base, primed for addiction by decades of prescription opiate use.

Then in 2014, fentanyl began entering the drug supply in large amounts.

Drug seizures containing fentanyl

What is fentanyl and why is it killing people?

Heroin is derived from opium, a plant. That means its growers need fields and labor to harvest the crop. They are tied to land, weather and time.

Fentanyl is purely synthetic. Think chemistry, not agriculture. It’s commonly used for surgical anesthesia and is prescribed to treat pain, but almost all of the fentanyl on the streets is illicitly manufactured. According to the Drug Enforcement Administration, the majority of illicit fentanyl in the United States is manufactured either in China or in Mexico using precursors bought from China. And at least some portion of it comes to the United States in the mail, ordered from dark web sources like the recently shuttered AlphaBay . But we don’t know how much.

Fentanyl is a fine-grained powder, meaning that it’s easy to mix into other drugs. This is how most people are exposed to illicit fentanyl: It will be mixed into, or made to look like, powdered heroin or it will be used to produce counterfeit prescription pills.

It’s super potent, meaning you’re dealing with very small quantities . That makes it almost impossible to control supply. Though most of the fentanyl in America is thought to originate in China, the fact that it’s synthetic means it’s much harder to know where the drugs are coming from. With heroin, investigators could rely on regionally specific chemical markers to indicate where the drugs had been produced. With drugs synthesized in a lab, it’s harder to tell .

Why would people take fentanyl? It does not sound fun.

From a dealer’s perspective, fentanyl is easier to get and more profitable to sell. Some law enforcement officials argue that drug users will seek out batches of drugs that contain fentanyl or that are known to have killed people, as that demonstrates the drugs’ potency.

While that is certainly true for some number of drug users , research suggests that they are a minority . Most are exposed to fentanyl inadvertently — it’s difficult to know just what is in the drugs they are buying (many dealers don’t know themselves), one more risk in a dangerous pursuit of a high.

For long-time drug users, their continued use underlines the grip of addiction and the agony of withdrawal: They know it could kill them but do it anyway. Casual drug users are also at risk of fentanyl poisoning, particularly with increased reports of fentanyl-adulterated cocaine.

So shouldn’t we just stop prescribing opioids?

Opioids are a vital component of modern medicine that have measurably improved the quality of life for millions of people, particularly cancer patients and those with acute pain. But their efficacy in treating chronic pain is less clear , especially when weighed against the risks of overdose and addiction.

Though prescription opioid consumption has been decreasing in the United States since 2010 or 2011, it remains high. According to the International Narcotics Control Board , if the amount of opioids prescribed per year were averaged out over each person living in America, everyone would get about a two-week supply. (Or a three-week supply, according to the C.D.C . Different ways of measuring what counts as a daily opioid dose give different values.) Either way you count, it’s higher than anywhere else in the world.

Average days of opioid use per resident per year

At the same time, some chronic pain patients now struggle to fill their prescriptions. Solving the opioid problem requires controlling prescription opioid distribution while maintaining access for patients with legitimate medical needs. Suddenly removing access to opioids from those who are dependent on them to function could easily push people to illicit opioid sources, like heroin or counterfeit pills.

What can be done?

Experts agree fixing the opioid epidemic will take a combination of solutions. But it’s a question of priorities: Which approaches will be most effective and most efficient? What is the best use of resources?

Officials want to use state prescription drug monitoring programs to reduce the supply of prescription opioids that end up being used recreationally while maintaining adequate access for current chronic pain patients. More broadly, experts say we need to improve the way our medical system manages pain. Remember the 12 million people we said took prescription painkillers outside of medical use? Roughly two-thirds of those did so to relieve physical pain . A more holistic approach to pain treatment would lessen the need for opioids .

On the treatment side, experts stress the importance of having treatment readily available for those who are already addicted. Often that means going to where the people are, not waiting for them to seek out treatment themselves. And addiction treatment doesn’t just mean counseling or an inpatient clinic. Studies show the most effective treatment for opioid addiction often requires opioid medications like methadone or buprenorphine .

In the meantime, widespread distribution of naloxone — an overdose antidote — will save lives in acute cases.

There isn’t agreement about other possible measures that could help. Public health experts advocate things like safe injection sites , where people could use drugs under medical supervision, and drug checking services that people could use to test drugs for fentanyl , but many in law enforcement remain reluctant to adopt such measures.

Will the commission’s recommendations help?

The commission laid out a series of recommendations in its interim report, with a final report expected in October.

Some of the recommendations — like enhancing prescription drug monitoring programs and mandatory physician education on the dangers of opioids — are aimed at prevention. Some — expanding access to and funding development of medication-assisted treatment, eliminating Medicaid barriers to in-patient addiction treatment and enforcing laws that prevent health insurance companies from limiting mental health coverage — are aimed at treatment. The commission’s report also called upon the president to mandate that naloxone be carried by every American law enforcement officer.

Of course, these are only recommendations. It’s up to the president and the various executive agencies to implement them. Experts know how to attack the problem. It’s just a matter of having the will to put those policies into practice.

What does declaring a national emergency actually do?

The commission’s “ most urgent recommendation ” was for Mr. Trump to declare a national emergency. One way this could work is through the National Emergencies Act and a law called the Public Health Service Act .

During a public health emergency, this law gives the secretary of health and human service broad authority to make grants, conduct investigations and waive or amend a variety of health regulations.

For example, the opioid commission argued that the H.H.S. secretary would be able to waive the I.M.D. exclusion, an obscure rule that bars Medicaid reimbursement for patients in mental health facilities with more than 16 beds. Since Medicaid pays for a significant portion of inpatient drug addiction treatment, the exclusion is a major obstacle.

Many states have been granted waivers from this regulation, but the onus is on each state to prove that it qualifies for one. The commission asserted that an emergency declaration would give the H.H.S. secretary the power to grant a waiver to any state that requests one, but it’s not clear that this is the case.

Do you have questions that we didn’t answer? Please let us know .

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‘The pain is so much.’ How stigma and shame over fatal overdose make grief more unbearable

One Sunday afternoon, days before Christmas, two police officers knocked on Janice Persson’s door in Ludlow, Massachusetts. Her son Brian, 30, was dead.

For years, Persson had offered support and calm reassurance to people when they felt scared or overwhelmed. She has worked as a nurse caring for organ transplant patients, staying by their side throughout their procedure and recovery.

But the news that her own son had died of an overdose put her “in total shock.” In the months that followed that December 2022 day, her marriage crumbled, as her husband blamed her for their son’s death, Persson, 59, said. She had never felt so alone.

“We’re not supposed to blame ourselves, but it’s hard,” she said through tears.

Every year, more than 100,000 people fatally overdose in the United States. While evidence suggests deaths from overdose have been declining overall , each death plunges loved ones left behind into a deep well of loss and grief.

“For every person who actually dies, there are lots of people involved in that person’s life,” said Dr. Anita Everett, who directs the Center for Mental Health Services within the Substance Abuse and Mental Health Services Administration.

As many as 125 million Americans know someone who fatally overdosed , according to one estimate. Another federal study suggests that between 2011 and 2021, more than 321,000 children lost a parent to overdose . But instead of receiving a kind word or a casserole, these families and friends often are confronted by stigma, shame and blame from strangers and neighbors alike. They may be told that their loved one’s death was self-inflicted or through some fault of their own.

READ MORE: Overdose fatalities fell last year, but the full picture is more complicated

Alison Athey led a study by the RAND Corporation published earlier this year in the American Journal of Public Health that estimated 2 in 5 U.S. adults know someone who has died from overdose.

The trauma and death toll tied to overdoses demands urgency “to think more creatively and more expansively,” Athey said. “There’s this huge gap that needs to be addressed from all sides.”

Nationwide, established support group networks exist for people with a parent, child or sibling who is struggling with substance use as they seek out treatment with the goal of entering recovery. But the same is not true for those who have witnessed that struggle end tragically, according to Everett.

Scarce resources for the bereaved

In the months that followed Brian’s death, Persson ached for her son and wished so many things had gone differently.

Once a happy boy and man, Brian thrived on adventure and in the outdoors — he “always liked to stay busy” and did well academically, Persson said.

But late in high school, she said, Brian experimented with drugs, sneaking into prescription pain medications at his family’s home before purchasing it elsewhere.

“I never saw the addiction, even as a nurse – no clue,” Persson said.

He eventually was placed in a rehabilitation program, where he recovered and relapsed. The cycle continued for years. Along the way, Persson said he was introduced to heroin, and he stole items from their home to sell in order to buy more heroin. By 2017, Persson said Brian “had to leave the house” after his father found drugs at home. Ultimately, he was arrested, convicted and sent to jail.

READ MORE: New study sheds light on ripple effects of overdose deaths

Upon his release less than a year later, Persson said Brian came home, found a job and began to build relationships with people, eventually dating the woman who became his fiancee. He experienced relapse (a normal part of recovery), but Persson said he immediately recommitted himself. During those four years before Brian’s death, Persson said, “We just were able to really see him.”

Then one Labor Day weekend, he got into a motorcycle accident, suffering injuries that required surgery. He missed time at work, stopped going to counseling and grew quiet about his relationship. Brian had relapsed again, and eventually fatally overdosed.

Consumed by guilt and grief, Persson tried to piece together how she had lost her son. Where had everything gone wrong? She thought of all the things she would have told him to try and save his life.

“Why couldn’t he have had one extra phone call?” she said.

She scoured the Internet for help to manage her sorrow. She found a support group in her hometown, but it was oriented toward families with loved ones in recovery, “or basically still alive,” she said. “It was too hard for me to go to those. It was a lot of PTSD.”

In Massachusetts, people who have endured what is sometimes called opioid bereavement or overdose bereavement have sought out each other, building camaraderie through grief as they figure out how to go on. They have started working with state agencies to build a more systematic approach in hopes of helping more people.

This work is important “because nobody does it,” said David Swindell, a grief counselor in Milford, Massachusetts, whose son, Chris, died of a fentanyl overdose in 2018.

Since 2000, more than 25,000 people have fatally overdosed in Massachusetts , according to the state Department of Public Health in December. Fentanyl has fueled many of those deaths, and state officials have ramped up an overdose prevention helpline, increased access to housing along with greater distribution of naloxone and fentanyl test strips. The state also has invested in prevention strategies, intervention, treatment and recovery services.

Beyond the Bay State, experts say resources for the bereaved are scarce. People from Michigan, Florida and California have joined Swindell’s virtual group therapy sessions because they don’t know whom else they can turn to closer to home. Researchers are looking to expand these supports in a way that’s sustainable and accessible, especially as overdose deaths continue to rise in more than a dozen states .

The pain of losing his son drives Swindell to work with families who have lost loved ones to the disease of addiction, he said. He and others also established Chris’ Corner Recovery Resource Center to throw a lifeline to people struggling with substance use.

“I’ve got to do something with this pain. This pain is so much,” Swindell said. “I’ve got to do something to help others. I don’t want anybody to go through this.”

“The light at the end of somebody’s tunnel might just be me.”

’A feeling of peace’

After months of struggle, a family friend and social worker suggested Persson contact Learn to Cope, a support group based in Easthampton, Massachusetts, for people experiencing opioid bereavement. When she did, Persson was matched with a peer support ally named Kathryn, who had also lost a son through similarly tragic circumstances a decade earlier.

Persson could contact Kathryn at any time, and they often texted back and forth. They talked about their sons, what they once did together, how they were feeling and what they were doing to stay active. They found comfort in sharing memories.

Beyond talking to her ally, Persson also joined the group’s virtual meetings with other people coping with the loss of a loved one due to overdose. Those interactions offered Persson “a feeling of peace,” she said, even as she managed “these waves [of grief] that come over you.”

“It was just so different to actually talk to someone who’s been through exactly what you were going through,” Persson said. Within that community, she did not encounter the stigma and shame that at times confronted her when she described her son’s struggle with addiction, recovery and relapse. “The more people talk about it, the more knowledgeable other people will be,” she said.

READ MORE: 6 tips on showing up for someone in mourning

Glen Lord, CEO for Peer Support Community Partners, his wife, Tanya Lord, and their colleague, Franklin Cook, have worked to create resources for people adrift in loss and grief after an overdose fatality, when the conversation is “shrouded in all this shame,” Tanya Lord said.

One of these projects includes SADOD, or Supporting After a Death by Overdose, which was founded in 2019 and is funded by the Massachusetts Bureau of Substance Addiction Services.

Stigma often silences families from being transparent about their loved one’s cause of death and asking for help when they’re in need of it themselves, Glen Lord said.

Talking about those who have died

Often, people don’t know what to say after someone dies, and that is especially true if the death was linked to overdose, Swindell said. This awkward tension can lead people to say nothing. That may feel safe, but it can compound the sense of isolation for the person who is grieving. Alternatively, people may say something hurtful, whether they mean to or not.

In one such instance, Swindell said he had gone to the cemetery to replace the candle at his son’s grave. While he sat there, an older man walked by and noticed the dates on the marker.

“‘How did he die?’” Swindell remembers the man asking.

“‘He died from substance use and addiction,’” Swindell replied.

“‘Oh, don’t worry,’” the stranger told Swindell. “‘God will forgive him.’”

Speechless, Swindell stared at the man until the stranger walked away.

People who want to support individuals in grief can do so in a few ways, according to Swindell.

READ MORE: What two decades of data on overdose suicides shows about mental health care disparities

Ask how they are doing and then “really listen and don’t judge,” he said. Do not give the “promise of false hope,” such as saying things like “it’ll get better” or “don’t worry, you’ll feel better,” because those assurances can come off as dismissive. Grief and healing are not linear, he added. A person may be years out from losing a loved one, but find themselves overcome with grief due to an anniversary, a sudden memory or a situation that brings back a flood of emotions.

If you happen to think spontaneously of someone’s deceased loved one, Swindell recommends telling that individual.

“They love hearing about their child or spouse or sibling being remembered – just being there for them,” he said. If a person who wants to offer support can remember the loved one’s birthday or the day they died, Swindell said, “even a simple text to say, ‘Hey, I’m thinking of you’ – something as simple as that is huge. It’s that connectedness that’s important.”

Keeping memories alive

An August baby, Brian loved to celebrate his birthday at the beach, Persson said. Their whole family used to gather and make good memories together in the gritty sand and brisk water every year. But last August, she did not know how to spend Brian’s birthday without him.

She called Kathryn. Her ally encouraged Persson to “do something special” to remember Brian. Persson thought of a group activity she had done with Learn to Cope months earlier where everyone quietly painted rocks and shared space with each other. It had brought calm to her: “To me, there was just this peace – something in the air.”

Persson asked the family to gather once more in Brian’s memory. The day before his birthday, they painted stones they had collected from the beach and remembered how much they loved him. On Aug. 1, his birthday, they scattered the rocks in a spot on the beach where Brian always walked to. If, in the future, people picked up the rocks left for Brian, it would be as if her son was traveling and seeing the world once more, Persson said.

As her family walked away, Persson’s 8-year-old niece – one of the youngest members of her family – lingered to talk. She looked up at Persson and said, “‘We should do this again next year.’”

Laura Santhanam is the Health Reporter and Coordinating Producer for Polling for the PBS NewsHour, where she has also worked as the Data Producer. Follow @LauraSanthanam

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Uptick in Drug Overdose Rates Is Widely Reported Especially Among Young Women

Increase of 356 percent recorded from 2010 to 2021.

Overdose rates in Colombia involving illegal opioids, hallucinogens, stimulants and sedative psychotropic medication increased greatly during 2018-2021, mainly caused by overdoses in young women, according to a study at Columbia University Mailman School of Public Health. Drug overdoses increased by 356 percent from 8.5 to 40.5 percent per 100,000 individuals from 2010 to 2021. The findings are published in the American Journal of Public Health .

The study is the first to describe national trends in overdose rates including prescribed and illegal substances and alcohol, across different population groups in Colombia.

“The pandemic in particular contributed to higher levels of distress and mental health problems including depression and anxiety in Colombia, similar to other countries,” said Silvia Martins , MD, PhD, professor of Epidemiology at Columbia Mailman School and senior author of the study. Higher prescriptions rates, and use of tranquilizers/sedatives/antidepressants in Colombia, during the pandemic, due to experiences of higher levels of anxiety, sadness, and difficulties to sleep, may have led to the overuse of drugs. This was more pronounced among women.”

Nearly 14 percent of people using substances in 2020 met criteria for a substance use-related disorder.

Based on results from the 2019 National Survey on Substance Use (CNSSU, Estudio Nacional de Consumo de Sustancias Psicoactivas de Colombia, 2019), the researchers found that substance use increased for most substances in the country in the past three decades, with only a small reduction in the prevalence of alcohol, cannabis, and cocaine use in 2019 compared to 2013.

To examine trends in overdose rates from 2010 to 2021, by type of substance, sex, age-group and intent as well as sociodemographic characteristics the researchers also used data from SIVIGILA—a national public health surveillance system, from 2010 to 2021, a mandatory notification system to determine health events.

The SIVIGILA data included 127,087 substance-use-related overdoses among people ages 10 and older, of which 54 percent were males, 75 percent were persons aged 10-34, 72 percent had at least some high school education or higher, and 51 percent and 38 percent respectively were individuals who either contributed to the health system or who were subsidized.

Information was used to group overdoses by substance type in the following categories: hallucinogens; stimulants (including prescription stimulants, cocaine, and methamphetamine); opioids (including prescription opioids, heroin, methadone and buprenorphine); inhalants; tranquilizers, sedatives and antidepressants; as well as cannabis. The researchers identified the most frequent combinations of multiple substances across the study period and the number of overdoses caused by these combinations.

The most frequently reported substances were tranquilizers/sedatives/antidepressants (43 percent), cannabis (16 percent)), stimulants (16 percent), alcohol (16 percent), and opioids (6 percent). The majority (95 percent), of stimulant overdoses were due to cocaine, while opioid overdoses were mostly due to prescription opioids (74 percent).

Overdose rates involving tranquilizers/sedatives/antidepressants and those involving opioids increased over the study period, growing at a faster rate after 2018. Drug overdoses involving cannabis and stimulants also increased until 2017 but decreased afterwards. Among women, the sharpest increase in overdose rates were for tranquilizers/sedatives/antidepressants, which increased faster from 2018 to 2021 (from 12 to 33 per 100,000, respectively).

More research on risk factors, motivations for use, and sources of these medications is needed to improve harm reduction interventions and policies,” observed Julian Santaella-Tenorio, DrPH, professor at Universidad Pontificia Javeriana in Cali, Colombia, former Columbia DrPH student, and first author of the study. “We also believe that suicide risk screening and access to complementary mental health care addressing suicidal ideation or behavior may improve health outcomes among individuals being prescribed these medications and those having recently experienced an overdose.”

“Addressing substance use challenges, including the emergence of novel drugs and of polysubstance use, is a complex task that requires a good understanding of the magnitude of the problem and the burden it imposes on populations and the health system,“ said Martins and Santaella-Tenorio.

It is possible that the decrease in the prevalence of cannabis and stimulants use in younger populations can be attributed to mobility restrictions during the COVID pandemic; reductions in these overdose rates may be also related to changes in consumption patterns that are less likely to result in overdose, noted the researchers.

According to Martins and Santaella, survey data likely underestimates the prevalence of drug use given that the CNSSU is a household survey that excludes populations with high-risk of drug use – i.e. homeless and incarcerated populations. In addition, overdoses not treated at health facilities are not included in the SIVIGILA data.

Over the past three decades, Colombia has transitioned to a human rights and public health-approach regulatory framework regarding substance use, an approach that is aligned with The United Nations Office on Drugs and Crime guidelines.

The findings suggest that additional prevention efforts are necessary, including harm reduction and community-based programs, and better access to treatment services that can reduce the risk on overdose in the population.

“Health surveillance systems are an important tool that can guide overdose prevention efforts in countries with limited data resources. While this particular study focuses on Colombia, their surveillance systems methodology can generate information for public health prevention efforts in other resource-poor countries,” noted Martins.

Co-authors are Jhoan Sebastian Zapata Lopez, Pontificia Universidad Javeriana, Colombia, Luis E. Segura, Columbia University Department of Epidemiology, Magdalena Cerda, NYU Department of Population Health, Thiago Fidalgo and Vitor Tardelli, Universidade Federal de São Paulo UNIFESP), Brazil.

The study was partially supported by a Columbia University Global Innovation Fund.

Media Contact

Stephanie Berger, [email protected]

Related Information

Meet our team, silvia martins, md, phd.

Director, Substance Use Epidemiology Unit
Affiliated Faculty, Institute of Latin American Studies
Affiliated Faculty, Global Mental Health Program
Affiliated Faculty, Columbia Population Research Center
Affiliated Faculty and Faculty Advisory Committee, Lemann Center for Brazilian Studies

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PDF Three Essays on the Broader Effects of the Opioid Crisis
overdose deaths reached almost 400% between 2010 and 2017. Another government response around the second wave was the expanded adoption of Prescription Drug Monitoring Programs (PDMPs). PDMPs are state-level policies, which have various levels of implementation. An electronic database allows for tracking controlled prescription drugs in a state.
PDF From the War on Drugs to Harm Reduction: Imagining a Just Overdose
overdose-related deaths were beginning to decline, the number of fatal overdoses among BIPOC individuals continued to rise in many cities across the country. 7 The pandemic has also disproportionately surged through these communities and has only compounded these disparities. People at risk of overdose are facing
The rising crisis of illicit fentanyl use, overdose, and potential
Introduction. Fentanyl was first developed in 1960 by Paul Janssen as a potent opioid anesthetic and analgesic. At the time, fentanyl was the fastest-acting opioid discovered to date and more powerful than morphine (50-100 times) and heroin (30-50 times) 1,2.Transdermal, intravenous, and transbuccal fentanyl administration and several other drugs with chemical structures that are similar ...
The Drug Overdose Problem Essay
Many people have been addicted to drugs and in some cases it has lead to death. Drug overdose can cause a lot of effects of someone's mind and body. Many lives are lost because of overdosing on drugs such as smoking, painkillers, and even alcohol. Overdosing has become more and more of a big problem over the years and could be very dangerous.
Ethics, Public Health, and Addressing the Opioid Crisis
Opioid misuse has become one of the gravest and most consequential public health threats facing the United States today. 1 Per the National Institutes of Health, the number of US drug overdose deaths has increased markedly over the past 2 decades, primarily due to the role of opioids. 2,3 In 2018, there were 67 367 drug overdose deaths in the ...
PDF FINAL FULL THESIS copy
I. Introduction. The United States is currently in the midst of a public health crisis. For. the past two decades, the growing opioid crisis, characterized by a. skyrocketing level of overdose deaths, has spread throughout the country. In 2017 alone, 47,600 people in the United States died from an opioid.
What led to the opioid crisis—and how to fix it
February 9, 2022 - Without urgent intervention, 1.2 million people in the U.S. and Canada will die from opioid overdoses by the end of the decade, in addition to the more than 600,000 who have died since 1999, according to a February 2 report from the Stanford-Lancet Commission on the North American Opioid Crisis. In this Big 3 Q&A, Howard Koh, professor of the practice of public health ...
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August 15, 2023 12:29 PM EDT. Hampton is a national addiction recovery advocate and author of two books on the overdose crisis: American Fix and Unsettled. His third book examining the modern ...
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Based on data from the National Vital Statistics System, 599,255 drug overdose deaths occurred from 1979 to 2016 in the United States, and the overall mortality rate has seen exponential growth.
Opioid Crisis in the US
West Virginia's opioid-related overdose death rate of 43.40 was one of the highest in the US in 2016 (Scholl, Seth, Kariisa, Wilson, & Baldwin, 2018, p. 1422). This is threefold higher than the national opioid-related overdose death rate of 13.3 in 2016 with a total of 42,249 drug overdose deaths (Scholl et al., 2018, p. 1422). In turn, West ...
Experience of Personal Loss Due to Drug Overdose Among US Adults
Drug overdose continues to be one of the most severe and long-lasting public health crises in the US. Since 1999, more than 1 million people have died from a drug overdose, with overdose death totals reaching more than 100 000 annually in 2021 and 2022. 1,2 Overdose is a contributor to the marked declines in life expectancy in the US, ...
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Essay On Return To Drug Use And Overdose After Release From Prison 1561 Words | 7 Pages. suffer from the use of drugs. Whether these be cocaine, heroin, LSD, marijuana, methamphetamine, or nicotine. The majority of these offenders end up in places such as prisons, leading to the issue of overcrowding.
Understanding the Opioid Overdose Epidemic
Drug overdose deaths. The number of people who died from a drug overdose in 2021 was over six times the number in 1999. The number of drug overdose deaths did not significantly change from 2021 to 2022. Over 75% of the nearly 107,000 drug overdose deaths in 2022 involved an opioid. 2021-2022. Opioid-involved death rates decreased by 12.5%.
How Drug Addiction Affects the Brain and Body
Some effects of drug abuse and addiction include changes in appetite, mood, and sleep patterns. More serious health issues such as cognitive decline, major organ damage, overdose, and death are also risks. Addiction to drugs while pregnant can lead to serious outcomes for both mother and child.
Opioid overdose
Opioid overdose. Opioid use can lead to death due to the effects of opioids on the part of the brain which regulates breathing. An opioid overdose can be identified by a combination of three signs and symptoms: difficulties with breathing. Worldwide, about 600 000 deaths were attributable to drug use in 2019.
Preventing, Recognizing, and Treating Opioid Overdose
More than 100,000 people died from drug overdoses from April 2020 to 2021, an increase of 28.5% from the prior year, according to a report by the Centers for Disease Control and Prevention (CDC). An opioid overdose can occur when a person: Overdoses on an illicit opioid drug, such as heroin or morphine; Overdoses on methadone
Opinion
Drug use is soaring, and drug overdoses are killing more than 100,000 people a year — more than at any other point in modern history. Life expectancy is declining in the United States for the ...
Short Answers to Hard Questions About the Opioid Crisis
Overdoses are merely the most visible and easily counted symptom of the problem. Over two million Americans are estimated to have a problem with opioids. According to the latest survey data, over ...
Addressing the Fentanyl Threat to Public Health
Opioid use, prescribing and fatal overdose patterns among racial/ethnic minorities in the United States: A scoping review and conceptual risk environment model, Drug and Alcohol Review, 43, 5 ...
FACT SHEET: Addressing Addiction and the Overdose Epidemic
Drug overdose deaths have reached a historic high, devastating families and communities. More than 104,000 Americans died due to a drug overdose in the 12-month period ending in September 2021 .
Case 37-2017
Dr. Alister M. Martin (Emergency Medicine): A 36-year-old man with opioid-use disorder was seen in the emergency department of this hospital during the winter because of opioid overdose.
Fentanyl-Associated Overdose Deaths Outside the Hospital
Drug-overdose deaths increased from 2016 through 2021 and were driven primarily by out-of-hospital deaths associated with fentanyl, which increased by 282% (from 46.6 per million to 178.0 per ...
'The pain is so much.' How stigma and shame over fatal overdose make
Left: Brian Persson, 30, died after a drug overdose in Massachusetts in 2022. His mother, Janice Persson, mourned his death and encountered stigma even as she grieved.
Uptick in Drug Overdose Rates Is Widely Reported Especially Among Young
Drug overdoses increased by 356 percent from 8.5 to 40.5 percent per 100,000 individuals from 2010 to 2021. The findings are published in the American Journal of Public Health. The study is the first to describe national trends in overdose rates including prescribed and illegal substances and alcohol, across different population groups in Colombia.

The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies

Yongbo Zheng

Introduction

Epidemic and evolution of illicit fentanyl use

Pharmacological mechanisms and side effects of fentanyl

Interventions for the management and prevention of fentanyl overdose

Acknowledgements

Conflict of interest

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Epidemic and evolution of illicit fentanyl use

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Interventions for the management and prevention of fentanyl overdose

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