Researchers share insights from US reduction of cigarette, sugar, and opioid consumption
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A case definition of market-driven epidemics (MDEs) could help address critical barriers to timely, effective prevention and mitigation, according to a study published this week in the open-access journal PLOS Global Public Health by Jonathan Quick from Duke University School of Medicine, US, and colleagues.
The misuse and overconsumption of certain consumer products have become major global risk factors for premature deaths at all ages, with their total costs in trillions of dollars. Progress in reducing such deaths has been difficult, slow, and too often unsuccessful. To address this challenge, Jonathan Quick and colleagues introduced a case definition of MDEs, which arise when companies aggressively market products with proven harms, deny these harms, and actively oppose mitigation efforts. To demonstrate the application of this concept, the researchers selected three MDE products: cigarettes, sugar, and prescription opioids. Based on the histories of these three epidemics, the researchers described five MDE phases: market expansion, evidence of harm, corporate resistance, mitigation, and market adaptation.
From the peak of consumption to the most recent available data, US cigarette sales fell by 82%, sugar consumption by 15%, and prescription opioid prescriptions by 62%. In each case, the consumption tipping point occurred when compelling evidence of harm, professional alarm, and an authoritative public health voice or public mobilisation overcame the impact of corporate marketing and resistance efforts. Among the three epidemics, the gap between suspicion of harm and the consumption tipping point ranged from one to five decades – much of which was attributable to the time required to generate sufficient evidence of harm. Market adaptation to the reduced consumption of target products had both negative impacts (eg, geographical shift of corporate marketing efforts) and positive impacts (eg, consumer shift away from sugar-sweetened beverages).
According to the authors, this is the first comparative analysis of three successful efforts to change the product consumption patterns of millions of people – and, over time, some of the associated adverse health impacts of these products. The MDE epidemiological approach of shortening the latent time between phases provides the global health community with a new method to address existing and emerging potentially harmful products and their health, social, and economic impacts.
While the specific product and circumstances are unique to each MDE, understanding the epidemiology of consumption and health impacts, and epidemic milestones, should help public health leaders combat current MDEs and more swiftly recognise future MDEs. Given the similar patterns among different MDEs, public health leaders, researchers, civil society and others can apply the mitigation strategies presented in the review article to save lives and lessen the impact of continuing and emerging MDEs.
The authors add: “The use of cigarettes and other unhealthy products costs the world millions of lives and trillions of dollars each year. An analysis of U.S. progress against three such market-driven epidemics demonstrates that we can save lives through earlier, more decisive action by public health leaders, researchers, and public mobilization,” concluding: “The use of cigarettes and other unhealthy products often follow patterns similar to infectious disease epidemics, causing widespread harm before any public health response. We can save lives by recognizing these market-driven epidemics earlier and acting more decisively to control them.”
Rehab centres in South Africa have been admitting an increasing number of codeine users in recent years. Now, the country’s medicines regulator has published a draft guideline as part of a broader effort to track suspicious codeine sales.
South Africa’s medicines regulator – the South African Health Products Regulatory Authority (SAHPRA) – has released a new draft guideline which it says will help stem the misuse of codeine. The opioid, which is found in certain pain relief medicines and cough syrups, is used by some people in large doses to get high.
Under the new draft guideline, the regulator can request sales data (and other information) from manufacturers, suppliers or distributors of any scheduled medicines. This would allow them to track the flow of codeine all the way “from the manufacturer to the dispensary, be it a clinic, pharmacy, hospital, or doctor’s practice”, SAHPRA’s communications officer, Nthabi Moloi, told Spotlight.
Why is this important? Until now, health authorities have struggled to detect suspicious sales of codeine, which is found in both prescription and over-the-counter medicines. This problem manifests in two ways. For one, recreational users can often get a continuous supply of codeine directly from pharmacies. While people are only permitted to purchase a limited amount of the drug, many bypass this simply by buying from different pharmacies. It’s largely impossible to flag these individuals since there is no centralised data on what medicines people buy across vendors (though attempts have been made to address this).
The second issue relates to wholesale supply. Following a Carte Blanche investigation flighted last year, SAHPRA confirmed that a pharmacy group was making illicit bulk sales of codeine-based cough syrups. While patients are only allowed to get codeine from a licensed health worker or pharmacist, it’s thus no surprise that it can also be found on the black market.
The new draft guideline aims to tackle both of these problems by allowing SAHPRA to request information from companies and health workers about how much codeine they’re producing, selling or dispensing and who it is being provided to. This would “enable SAHPRA to detect anomalies in the distribution of medicines prone to abuse, such as abnormally large orders by dispensaries” Moloi explains.
It is the “first phase”, she says, of the codeine care initiative – which is an effort to centralise data on all codeine sales along the entire supply chain nationally. The plan is to ensure that the regulator can flag anything from an individual who is buying large amounts of codeine from multiple vendors to a wholesaler who is selling the drug to illicit dealers.
Codeine rehab admissions triple since 2019
The draft guideline, which is now available for public comment, comes at a time in which rates of codeine addiction are soaring throughout South Africa, according to admissions data from drug and alcohol treatment facilities. Most rehabilitation centres around the country are connected to a programme called the South African Community Epidemiology Network on Drug Use (SACENDU), which collects anonymised patient data from the different centres. Professor Nadine Harker, who oversees this project says “if you look at treatment admissions over time, there has been an increase [in codeine-related admissions] over the years – steadily but definitely”.
Indeed, SACENDU’s bi-annual reports show that in the first half of 2019, 277 people who went to SACENDU-linked rehab sites said they had been misusing codeine. This amounted to 3% of all admissions. But by the first half of 2023, this percentage had tripled to 9% – totalling 749 people. (In absolute terms the number slightly less than tripled).
Even before this uptick, health workers were concerned. In the mid-2010s, a survey of 238 (mostly private sector) doctors was conducted across South Africa. It found that 85% of these practitioners were worried about the easy availability of codeine in pharmacies.
Part of the concern is driven by the fact that people who use codeine-based medicines over a long time can develop a range of health complications, including stomach ulcers and liver damage (this is particularly when the medicines contain additional substances like paracetamol). And some people are more vulnerable than others, as genetic factors play a big role in how codeine affects a person.
Why is the problem getting worse?
Part of the spike in codeine use appears to be driven by a trend among young people, who sometimes mix codeine-based cough syrups with cooldrinks. The combination is often referred to as lean, and has become a popular party drug among high school students. Research shows that codeine’s low price and general accessibility is one reason for its popularity. Harker for instance notes that it’s often available at home, where kids “can pick it up out of their mom’s medicine cabinet”.
In other cases, people appear to be relying on the drug not for recreation but to cope with psychological distress. For instance, a 2022 study for which women were interviewed at rehab centres in the Western Cape and Eastern Cape found that many had turned to pharmaceutical products to deal with everything from trauma caused by physical abuse to grief over the loss of a child.
“I just wanted the pain to go away. I wanted my mind to switch off… [the tablets] actually made me dead inside if I can say that,” one woman explained.
A lack of awareness about the dangers of codeine also seems to play a role: 94% of doctors who were surveyed agreed that patients “do not fully understand the risk of dependence in taking over-the-counter medicines containing codeine”. The lack of regulatory control may contribute to this impression: one study at South African rehab centres found that “many participants were of the view that [over-the-counter] codeine-containing medicines were not drug[s] per se due to their free availability to purchase without any real regulations or protocols guiding their sale”.
Shouldn’t we just make codeine prescription-only?
Currently, the law states that codeine-based pills can be bought over the counter only under specific conditions. For one, they have to contain another active ingredient like paracetamol or ibuprofen, and each pill can contain a maximum of 10 milligrams of codeine. A person can only buy one pack and it must contain at most 5 days’ worth of medicine (with no more than 80 milligrams a day). Anything more and a script is needed.
Liquid codeine, like cough syrups, can be bought without a script if it contains no more than 10 milligrams of codeine per teaspoon (the maximum daily dose is 80 milligrams). The bottle itself may not contain more than 100 millilitres of syrup.
Products like Gen-payne, Myprodol, and Stopayne all contain small amounts of codeine – typically in combination with other painkillers such as paracetamol or ibuprofen. (Photo: Towfiqu Barbhuiya/Unsplash)
Some researchers that spoke to Spotlight argue these restrictions are too lenient, and that codeine should be ‘up-scheduled’, meaning that it would only be available if a patient has a script, regardless of the dose or combination. By doing this, children may find it harder to get a hold of cough syrups for lean, and people may generally become more aware of the addictiveness of the drug when used over the long-term.
Indeed, there are some studies which have found this approach to be effective in other countries. Research published in the journal Addiction found that when authorities in Australia made codeine prescription-only in 2018, a large poisoning information centre in the country began to receive significantly fewer calls about codeine-related incidents (both from health workers and members of the public).
But there are also potential downsides to this strategy. For one, as Spotlight has previously reported, increased regulation may make life harder for poorer patients seeking pain relief. This is given that they would have to spend more money for a consultation and prescription if they needed codeine-based painkillers.
Andy Gray, who chairs an advisory scheduling committee at SAHPRA, details a second issue: “I’m not convinced that up-scheduling would solve the issue if what we’re dealing with [in South Africa] is illegal behaviour… If [codeine] is being smuggled out of manufacturers or wholesalers, scheduling is not going to make a difference”.
Dr Andrew Scheibe, a harm reduction researcher at the University of Pretoria, notes a third related problem that may occur. “If people do have codeine-dependence and they’re unable to access the codeine, they might likely shift to accessing opioids… on the black market”.
Scheibe highlights the United States as an example, where prescription opioids like oxycodone and fentanyl have been at the centre of a major drug epidemic. “When they tried to increase restrictions on access to those opioids then people started using heroin,” he notes. A 2022 study found that this had taken place among opioid users interviewed in Connecticut, Kentucky and Wisconsin.
Whatever the answer, researchers agree that some basic steps need to be taken to educate the public. Harker says “a lot of awareness raising needs to happen at various levels, for instance at pharmacies”. She notes that “when someone purchases codeine over the counter, it’s important for a pharmacist to engage [with them and] make the consequences known to the individual if they use it outside of the dosages indicated… And we don’t do that enough from the medical or pharmacist’s side”.
The number of patients admitted with opioid use disorder (OUD) and injection-related infections who left the hospital before completing treatment increased significantly between 2016 and 2020 (from 9.3% to 17%) according to analysis from researchers at the Perelman School of Medicine at the University of Pennsylvania. One in six of these patients now leave the hospital before medically advised (BMA).
The findings, published in JAMA, also reveal that the rate at which patients with any opioid-related issues (patients presenting with other issues but exhibiting opioid dependence) left the hospital BMA increased more than 50% (from 7.5 to 11.3%). In both of these groups, nearly half of BMA discharges occurred before the third day, when withdrawal symptoms are most severe. Now that fentanyl has become the dominant opioid causing overdoses, the findings illustrate the need for patient-centred care that adequately manages pain and withdrawal symptoms so that patients can complete treatment.
Approximately 500 000 patients are discharged against medical advice, or in the United States annually, and those circumstances are associated with increased likelihood of death and hospital readmission. Previous research shows that patients with addiction cite withdrawal and pain as their reason for BMA discharge.
“The rapid increase in early discharges is alarming; in 2016, less than one in ten patients admitted for OUD and injection-related infections left the hospital before their care team considered it safe. By 2020, one in six were leaving early,” said lead author Ashish Thakrar, MD. “What’s more, since the study period ended, the COVID-19 pandemic caused the opioid crisis to escalate, underscoring just how urgent it is to understand how we might be able to reverse this trend and get patients the treatment they need.”
Using nationally representative data from the National Readmissions Database, researchers compared the rate of discharge BMA in patients admitted for OUD to the BMA discharge rate for non-opioid admissions. They also evaluated changes in the proportion of BMA discharges before the third admission day, when opioid withdrawal is most severe, and changes in the proportion of discharges BMA in patients with stimulant use disorder.
They identified opioid-related admissions as those with opioid use, dependence, abuse, or overdose. To account for patients who were more likely to have severe OUD and fentanyl use, they also included patients with OUD and an injection related infections, such as bacteraemia, endocarditis, or osteomyelitis.
Between 2016 and 2020, they found that the number of patients admitted with OUD and injection-related infections who left the hospital BMA increased 82%, from 9.3% to 17%. They also found that the discharge BMA rate for all opioid-related admissions increased 50% during this period, from 7.5% to 11.3%. The proportion of BMA discharges occurring before the third day also increased for individuals with OUD and an injection-related infection, from 42.6%, to 48%.
In contrast, the BMA rate increased only marginally for non-opioid mental health or substance use admissions, and all non-opioid admissions (from 3.1 to 3.5%, and 1.1 to 1.5%, respectively).
“These data didn’t allow us to discern which type of opioid that individuals were using when admitted for OUD, but we know that fentanyl, an opioid 25 to 50 times more potent than heroin, has spread in unregulated drug supplies and is now involved in 88 percent of opioid overdoses in the US. Withdrawal symptoms from fentanyl are more difficult to manage than from other opioids like heroin and oxycodone,” said Thakrar. “This study illustrates why we need more research on how to manage individuals withdrawing from fentanyl and other substances in the unregulated drug supply.”
“The drugs that individuals are using have changed over the past decade, and how we treat them should change, too,” said senior author M. Kit Delgado, MD, MS. “Health systems can expand the use of interventions that are already proven to treat withdrawal and reduce but not widely used, such as medications like buprenorphine and methadone.”
Thakrar and Delgado also suggest that hospitals could be incentivised to reduce discharges BMA and to support specialty services such as addiction consult services that have been proven to reduce BMA discharges and that can reduce the risks of future readmission or death.
Women have long been known to outlive men. But new research published in JAMA Internal Medicine shows that, at least in the United States, the gap has been widening for more than a decade. Among the factors driving the trend are the COVID pandemic and the opioid overdose epidemic.
The study, led by UC San Francisco and Harvard T.H. Chan School of Public Health, found the difference between how long American men and women live increased to 5.8 years in 2021, the largest since 1996. This is an increase from 4.8 years in 2010, when the gap was at its smallest in recent history.
The pandemic, which took a disproportionate toll on men, was the biggest contributor to the widening gap from 2019–2021, followed by unintentional injuries and poisonings (mostly drug overdoses), accidents and suicide.
“There’s been a lot of research into the decline in life expectancy in recent years, but no one has systematically analysed why the gap between men and women has been widening since 2010,” said the paper’s first author, Brandon Yan, MD, MPH, a UCSF internal medicine resident physician and research collaborator at Harvard Chan School.
Life expectancy in the US dropped in 2021 to 76.1 years, falling from 78.8 years in 2019 and 77 years in 2020.
The shortening lifespan of Americans has been attributed in part to so-called “deaths of despair.” The term refers to the increase in deaths from such causes as suicide, drug use disorders and alcoholic liver disease, which are often connected with economic hardship, depression and stress.
“While rates of death from drug overdose and homicide have climbed for both men and women, it is clear that men constitute an increasingly disproportionate share of these deaths,” Yan said.
Interventions to reverse a deadly trend
Using data from the National Center for Health Statistics, Yan and fellow researchers from around the country identified the causes of death that were lowering life expectancy the most. Then they estimated the effects on men and women to see how much different causes were contributing to the gap.
Prior to the COVID pandemic, the largest contributors were unintentional injuries, diabetes, suicide, homicide and heart disease.
But during the pandemic, men were more likely to die of the virus. That was likely due to a number of reasons, including differences in health behaviours, as well as social factors, such as the risk of exposure at work, reluctance to seek medical care, incarceration and housing instability. Chronic metabolic disorders, mental illness and gun violence also contributed.
Yan said the results raise questions about whether more specialised care for men, such as in mental health, should be developed to address the growing disparity in life expectancy.
“We have brought insights to a worrisome trend,” Yan said. “Future research ought to help focus public health interventions towards helping reverse this decline in life expectancy.”
Yan and co-authors, including senior author Howard Koh, MD, MPH, professor of the practice of public health leadership at Harvard Chan School, also noted that further analysis is needed to see if these trends change after 2021.
“We need to track these trends closely as the pandemic recedes,” Koh said. “And we must make significant investments in prevention and care to ensure that this widening disparity, among many others, do not become entrenched.”
Strategies to treat pain without triggering dangerous side effects such as euphoria and addiction have proven elusive. For decades, scientists have attempted to develop drugs that selectively activate one type of opioid receptor to treat pain while not activating another type of opioid receptor linked to addiction. Unfortunately, those compounds can cause a different unwanted effect: hallucinations. But a new study published in the journal Nature has identified a potential route to pain relief that neither triggers addiction nor activates the pathway that causes hallucinations.
Painkilling drugs such as morphine and oxycodone, as well as illegal street drugs such as heroin and fentanyl, activate what are known as mu opioid receptors on nerve cells. Those receptors relieve pain but also cause euphoria, contributing to addiction. An alternative strategy is to target another opioid receptor, called the kappa opioid receptor. Scientists attempting to make drugs that target only the kappa receptor have found that they also effectively relieve pain, but they can be associated with other side effects such as hallucinations.
Research led by Washington University School of Medicine in St. Louis has identified the potential mechanisms behind such hallucinations, with the goal of developing painkillers without this side effect. Using electron microscopes, the researchers identified the way that a natural compound related to the salvia plant selectively binds only to the kappa receptor but then causes hallucinations.
“Since 2002, scientists have been trying to learn how this small molecule causes hallucinations through kappa receptors,” said principal investigator Tao Che, PhD, an assistant professor of anesthesiology. “We determined how it binds to the receptor and activates potential hallucinogenic pathways, but we also found that other binding sites on the kappa receptor don’t lead to hallucinations.”
Developing new drugs to target these other kappa receptor binding sites may relieve pain without either the addictive problems associated with older opioids or the hallucinations associated with the existing drugs that selectively target the kappa opioid receptor.
Targeting the kappa receptor to block pain without hallucinations would be an important step forward, according to Che, because opioid drugs that interact with the mu opioid receptor have led to the current opioid epidemic, causing more than 100 000 overdose deaths in the US in 2021.
“Opioids, especially synthetic opioids such as fentanyl, have contributed to far too many overdose deaths,” Che said. “There’s no doubt we need safer pain-relieving drugs.”
Che’s team, led by first author Jianming Han, PhD, a postdoctoral research associate in Che’s laboratory, found that a class of signaling proteins called G proteins cause the kappa opioid receptor to activate several different pathways.
“There are seven G proteins linked to the kappa receptor, and although they are very similar to each other, the differences between the proteins may help explain why some compounds can cause side effects such as hallucinations,” Han said. “By learning how each of the proteins binds to the kappa receptor, we expect to find ways to activate that receptor without causing hallucinations.”
The function of the G proteins has largely been unclear until now, particularly the protein that activates the pathway lined to hallucinations.
“All of these proteins are similar to one another, but the specific protein subtypes that bind to the kappa receptor determine which pathways will be activated,” Che said. “We have found that the hallucinogenic drugs can preferentially activate one specific G protein but not other, related G proteins, suggesting that beneficial effects such as pain relief can be separated from side effects such as hallucinations. So we expect it will be possible to find therapeutics that activate the kappa receptor to kill pain without also activating the specific pathway that causes hallucinations.”
Acute low back pain is a common cause of disability, and while opioid drugs are effective at controlling pain, excessive use creates a great potential for substance abuse. An analysis in the Journal of Orthopaedic Research examined which non-opioid drugs are best for relieving this pain.
The analysis, which included all randomised controlled trials published to date (18 studies with 3478 patients), showed that muscle relaxants and non-steroidal anti-inflammatory drugs (NSAIDs) could effectively and rapidly reduce symptoms.
The combination of NSAIDs and paracetamol was associated with a greater improvement than NSAIDs alone.
“This is a first step towards the optimisation of the management of acute low back pain. However, specific patient characteristics such as having allergies and comorbidities must always be taken into consideration,” said lead author Alice Baroncini, MD, PhD, of RWTH University Hospital in Germany. “Further research will need to focus on the identification of the type of drugs that not only offer the best and quickest pain relief, but also show the lowest rate of symptom recurrence.”
Researchers have developed a vaccine that blocks fentanyl’s to enter the brain, thus eliminating the dangerous synthetic opioid’s “high”. The breakthrough discovery, reported in the journal Pharmaceutics, could have major implications for the rampant problem of opioid addiction by becoming a relapse prevention agent for people trying to quit using opioids.
While Opioid Use Disorder (OUD) is treatable, studies estimate that 80% of those dependent on the drug suffer a relapse. Fentanyl is 50 times stronger than heroin and 100 times stronger than morphine. Consumption of about 2mg of fentanyl (the size of two grains of rice) is likely to be fatal depending on bodyweight. Current treatments for OUD are methadone, buprenorphine and naltrexone. Naloxone is given in opioid overdose situations and can temporarily reverse the effects of the opioids.
“We believe these findings could have a significant impact on a very serious problem plaguing society for years – opioid misuse. Our vaccine is able to generate anti-fentanyl antibodies that bind to the consumed fentanyl and prevent it from entering the brain, allowing it to be eliminated out of the body via the kidneys. Thus, the individual will not feel the euphoric effects and can ‘get back on the wagon’ to sobriety,” said lead author Colin Haile, a research associate professor of psychology at University of Houston.
No any adverse side effects from the vaccine were observed in trial animals. The team plans to start manufacturing clinical-grade vaccine in the coming months with clinical trials in humans planned soon.
Fentanyl is an especially dangerous threat because it is often added to street drugs like cocaine, methamphetamine and other opioids, such as oxycodone and hydrocodone/acetaminophen pills, and even to counterfeit benzodiazepines like Xanax. These counterfeit drugs laced with fentanyl add to the amount of fentanyl overdoses in individuals who do not ordinarily consume opioids.
“The anti-fentanyl antibodies were specific to fentanyl and a fentanyl derivative and did not cross-react with other opioids, such as morphine. That means a vaccinated person would still be able to be treated for pain relief with other opioids,” said Haile.
The vaccine tested contains an adjuvant derived from E. coli named dmLT. An adjuvant molecule boosts the immune system’s response to vaccines, a critical component for the effectiveness of anti-addiction vaccines.
Therese Kosten, professor of psychology and director of the Developmental, Cognitive & Behavioral Neuroscience program at UH, calls the new vaccine a potential “game changer.”
“Fentanyl use and overdose is a particular treatment challenge that is not adequately addressed with current medications because of its pharmacodynamics and managing acute overdose with the short-acting naloxone is not appropriately effective as multiple doses of naloxone are often needed to reverse fentanyl’s fatal effects,” said Kosten, senior author of the study.
Over the past 21 years of opioid overdose deaths in the US, whether an area is urban or rural has played a role in where opioid-involved overdose deaths have occurred, reports a new study published in JAMA Network Open. But there will no longer be a distinction between these, the study suggests – and there will be a dramatic increase in opioid-related overdoses.
The reason opioid overdoses have reached historical highs comes from combining synthetic opioids with stimulants such as cocaine and methamphetamines, a lethal cocktail that is hard to reverse during an overdose, the study authors said.
“I’m sounding the alarm because, for the first time, there is a convergence and escalation of acceleration rates for every type of rural and urban county,” said corresponding author Lori Post, director of the Buehler Center for Health Policy and Economics at Northwestern University Feinberg School of Medicine. “Not only is the death rate from an opioid at an all-time high, but the acceleration of that death rate signals explosive exponential growth that is even larger than an already historic high.”
Using methods developed to track COVID outbreaks, the study examined geographic trends in opioid-involved overdose deaths between 1999 and 2020 to determine if geography played a role in the three waves and the theorised fourth wave of America’s opioid crisis.
Near the end of the available data from 2020, overdose deaths in rural areas were escalating faster than in urban areas, according to the study. A visualization of the data illustrates that between 2019 and 2020, rates of opioid-involved overdose deaths converged while escalating for the first time across six types of rural and urban counties, Post said.
“We have the highest escalation rate for the first time in America, and this fourth wave will be worse than it’s ever been before,” Post said. “It’s going to mean mass death.”
The study authors examined toxicology reports and found people are using fentanyl (50 to 100 times more potent than morphine) and carfentanil (approximately 100 times more potent than fentanyl) combined with methamphetamines and cocaine. The result is a powerful and lethal cocktail that can even evade help from overdose-reversing drugs like naloxone.
“The stronger the drugs, the harder it is to revive a person,” said study co-author Alexander Lundberg, assistant professor of emergency medicine at Feinberg. “The polysubstance use complicates an already dire situation.”
“It appears that those who have died from opioid overdoses had been playing pharmacist and trying to manage their own dosing,” Post said. “This is a bigger problem because you have people misusing cocaine and methamphetamines along with an opioid, so you have to treat two things at once, and the fentanyl is horribly volatile.”
“The only path forward is to increase awareness to prevent opioid use disorders and to provide medication-assisted treatment that is culturally appropriate and non-stigmatising in rural communities,” Post said.
While the pandemic era has seen global supply chains strained and medicines running short even in the developed world, it was not the case with prescription opioids, namely oxycodone and hydrocodone in the early 2000s. In fact, the opposite was true, argues a study published in the Journal of Supply Chain Management: supply chains became so efficient that they produced a glut of opioids that helped spark the opioid crisis in the US that has since spread to other parts of the world.
This supply glut is partly due to the influence of supplier pool pressure on pharmacy participation in oversupply, according to research conducted by Ednilson Bernardes, professor at the West Virginia University John Chambers College of Business and Economics.
Simply put, pressure exerted by manufacturers and suppliers of opioids, particularly national corporations, influenced how pharmacies bought and distributed those prescriptions.
“We argued that when the pool of suppliers has cohesive expectations for how buyers should behave and sufficient power to dominate the supply relationship, then buyers are under pressure to act in line with those expectations,” Prof Bernardes said.
Prof Bernardes and co-author, Paul Skilton of Washington State University, analysed transactions involving oxycodone and hydrocodone between 2006 and 2012. They chose those two drugs, Prof Bernardes said, because they’re the most commonly abused, legally prescribed products and central to the American opioid epidemic.
The researchers tested a model using a dataset combining geographic, market and public health data. The model revealed that more than 90% of supply originated with three generics manufacturers that aggressively competed for shelf space in distributors and pharmacies.
Bernardes explained how several factors led to opioid oversupply, which occurs when ordinary production and distribution processes deliver products in excess of the safe needs of a market.
“First, even though pharmacists, suppliers and manufacturers knew the products were toxic, physicians were prescribing the products,” Bernardes said. “Second, although the DEA (US Drug Enforcement Agency) expected the companies selling opioids to report unusually large purchases, it put no controls to ensure that they did. Third, even if they had, individual transactions were typically small but made up very large totals.
“Under these conditions, the whole supply chain could produce far more of these products than were good for patients or society. While it is a system-level phenomenon, we theorize that it emerges from individual behaviours and that the actions of suppliers and competitors influence those behaviours in addition to demand from patients.”
In addition, Bernardes said market characteristics, such as demand, regulation and market population size, influenced pharmacy participation.
“Supplier pools can impose their expectations only if they have greater bargaining power than buyers or if buyers critically depend on them,” Bernardes said. “Pharmacies are critically dependent on the opioid supplier pool, which is regulated at the federal and state level, because opioids are an important contributor to supplier and pharmacy profitability.”
Bernardes and his colleague believe this study blazes a trail for further supply chain research as it develops a novel notion of oversupply, distinct from the traditional idea of excess inventory, and normal misconduct that explain how pressures within supply chains shape misconduct beyond the opioid context.
The research is also unique, Bernardes said, because previous studies focused primarily on firm-level consequences of behavior such as supplier sustainability risk and corrupt opportunism. The focus on firm-level outcomes leaves a gap in understanding systemic factors that normalize misconduct in supply chains.
“The phenomenon exposes supply chain behaviour that is widespread and persistent despite its negative consequences for society,” Bernardes said. “Examples include products that harm consumers and business models that degrade the environment, exploit labour or perpetuate social injustice.”
In a bid to tackle the global opioid crisis, researchers have found that a Chinese medicinal plant extract can prevent morphine tolerance and dependence while also reversing opiate addiction. The researchers published their results in Pharmaceuticals.
For over two decades, opioid analgesic overprescription has driven a wave of misuse and consequent drive overdose deaths around the world, with the number of drug overdose deaths tripling in the US from 1997 to 2017. The COVID pandemic has only worsened the opioid epidemic. Fortunately, the documented effects of YHS, the extract of the plant Corydalis yanhusuo, could help curb the opioid epidemic.
“It is critical that we decrease the use and abuse of opiates,” said Olivier Civelli, PhD, professor of pharmaceutical sciences at the UCI School of Pharmacy & Pharmaceutical Sciences and corresponding author. “To help achieve this goal, we are proposing the use of this therapeutic plant. When used in animals, the Corydalis extract prevents pain and the negative effects of opiate use. The next step would be to test it with humans.”
The overprescription of opioid analgesics stemmed from treatment of chronic pain requiring repeated opioid administrations. This ultimately leads to tolerance, physical dependence, and addiction.
One possible solution involves a co-medication that maintains the analgesic benefits of opioids while preventing their adverse liabilities. The study showed that YHS, when co-administered with morphine, inhibits morphine tolerance, dependence and addiction.
In Chinese traditional medicine, YHS has been used as an analgesic for centuries. It is considered safe and readily available for purchase. “Opiate tolerance is of utmost importance to opiate users,” ProfvCivelli said. “They need to constantly increase the need of opiates to reach the same analgesic response. This is what leads to opiate overdose. YHS prevents opiate tolerance, so there is less need to increase opiate consumption.”
