Anatomy of a tragedy: the global opioid epidemic
Over the last 25 years, the world has suffered a global epidemic of drug abuse that has claimed the lives of close to a million people, and still shows no signs of ending. This article discusses the ways that opioids work, as well as their benefits and downsides – including the risk of addiction, dependence, and overdose. We show how today’s global opioid crisis started with overprescribing of legal drugs, before moving on to fresh waves of devastation driven by heroin and synthetic opioids like fentanyls. We also explain why there has never been a more dangerous time to take street drugs than today – due to the rapid emergence of ever-stronger opioid drugs like nitazenes, and hundreds of illicit New Psychoactive Substances (NPS).
What are opioids, and why are they a problem?
Opioid drugs come in three main forms: natural, semi-synthetic and synthetic. Natural opioids like codeine, morphine, and opium, derive from seed pods of the poppy plant Papaver somniferum. Semi-synthetic opioids such as heroin, hydrocodone (Vicodin), and oxycodone (OxyContin), are more potent drugs synthesised from codeine or morphine - whereas synthetic opioids including methadone, tramadol and fentanyl, are totally artificial and often more powerful still. For example, fentanyl is up to 100 times stronger than morphine.
Medicinal opioids are designed mainly for treating moderate to severe pain, and for use in anaesthesia. They work by attaching themselves to one of three opioid receptors on the body’s nerve cells – known as Mu, Kappa, and Delta receptors (MORs, KORs, and DORs). Activating opioid receptors essentially "block(s) pain messages sent from the body through the spinal cord to the brain,” and can result in a sense of well-being or euphoria, as well as reduced anxiety and sedation. But the feelings of pleasure that result from taking opioids can also lead users to develop conditions such as opioid dependence (when they experience unpleasant withdrawal symptoms), or opioid tolerance (when they need to use more drugs to achieve the same effects). High doses of opioid drugs can also slow a person’s breathing and heart rate enough to cause their death – a risk that applies to prescription and street drugs alike.
Waves of devastation – how the global opioid crisis unfolded
Between 1999 and 2022, there were more than 1.1 million fatal drug overdoses in the United States (US), with almost 727,000 of them caused by prescription or illicit opioids. Declared a public health emergency and a “national shame” by President Trump in 2018, America’s opioid crisis developed in four distinct “waves” of drug abuse – the first three driven by prescription opioid pills (first wave, from 1999), heroin (second wave, from 2010), and synthetic opioids (third wave, from 2013).
The first wave – prescription opioids
According to the US Centers for Disease Control and Prevention (CDC), the first wave began with “increased prescribing of opioids in the 1990s”, leading to a rise in overdose deaths from legal opioids from around 1999. In the words of The Lancet, this catastrophic rise in opioid prescriptions was due at least in part to “Years of aggressive and misleading promotion by Purdue Pharma (the maker of the billion dollar painkiller Oxycontin), which entrenched misinformation that opioids were without risk.” Professor Judith Feinberg, from the West Virginia University School of Medicine, believes that prescribing opioids also became widespread because many Americans’ health insurance would not cover anything but a pill. “Say you have a patient that’s 45 years old. They have lower back pain, you examine them, they have a muscle spasm,” she told the BBC. “Really the best thing is physical therapy, but no one will pay for that. So doctors get very ready to pull out the prescription pad.”
The second wave – heroin
In time, doctors, health authorities and governments began to harbour “considerable concern.... regarding prescribing rates of opioids... and the awareness of healthcare professionals and patients of the risks of dependence and addiction.” This led to crackdowns on the overuse of overuse of potentially addictive medicines, which in the United Kingdom (UK) helped cut opioid prescriptions by 450,000 in less than four years. In the US, the number of hydrocodone and oxycodone pills prescribed fell 45% between 2011 and 2019 – but may also have pushed addicts into using illegal drugs like heroin instead, inadvertently fuelling the second wave of the opioid crisis. “We created a huge cohort of people dependent on opioid pills and when we pulled back on those, we created a heroin wave...” Daniel Ciccarone, from the University of California at San Francisco School of Medicine, told The Washington Post.
LGC Standards – supporting your opioid and NPS analysis and research
Knowing the precise levels and types of opioids in the body – via laboratory analysis of biological samples such as blood, urine, hair, and saliva – is essential in both forensic investigations and clinical toxicology.
This analytical testing helps us to understand the role of opioids and New Psychoactive Substances (NPS) in cases related to overdose, substance abuse and death – supporting both accurate diagnosis and appropriate treatment in clinical settings, as well as crime investigations and legal proceedings.
Researchers meanwhile need to develop new analytical techniques to keep up with the large number of new drugs that are appearing in illicit markets, since understanding their pharmacological effects, metabolic pathways and health risks can lead to both better treatments and control measures.
LGC Standards offers a diverse portfolio of more than 1,000 reference materials and research chemicals for opioids and opiates from Logical, Lipomed, and TRC- including key metabolites, stable isotopes and matrix materials, neats, single solutions and mixtures. This in-house collection, which includes over 120 ISO 17034-accredited standards, is complemented by 600+ products from leading third-party manufacturers.
Our extensive New Psychoactive Substance range meanwhile helps laboratories to meet rapidly changing analytical demands – with more than 2,000 NPS reference materials and research chemicals for cathinones, fentanyls, nitazenes, phenethylamines, piperazines, synthetic cannabinoids, tryptamines, and more – almost 500 of them ISO 17034-compliant.
To complete your opioids and NPS toolkit, AXIO Proficiency Testing also offers four toxicology and clinical proficiency testing schemes - QUARTZ, DAH, DOF, and DAU - which together enable your laboratory to assess and demonstrate its competence in analysing drugs of abuse in blood, urine, oral fluid and hair matrices.
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The third wave – synthetic opioids
By 2013, the third wave of the US opioid crisis had begun, fuelled by “substantial increases in overdose deaths involving synthetic opioids, particularly those involving illegally made fentanyl and fentanyl analogs (IMFs).” IMFs, the CDC says, quickly “saturated the illegal drug supply”, and by 2016 fentanyl was already killing more people in the US than either prescription opioids and heroin. Between 2015 and 2021, IMFs were the main drivers of a more than seven-fold increase in synthetic opioid-related deaths in the US – from 9,580 to 70,601 – and the problem had also begun to spread beyond America’s borders.
Between 2019 and 2021, more than a quarter of all deaths amongst Canadians aged between 20 and 39 were related to opioids, with total opioid deaths in that country rising from 3,007 to 6,222 in the same period, and to 7,500 the following year. Synthetic opioids are also a “significant problem” in some European countries, according to the 2024 European Drug Report, with “the potential to play a larger role in Europe’s drug problems in the future.” At least 163 deaths were associated with fentanyl and fentanyl derivatives in Europe in 2022, while the UN also says that the abuse of another synthetic opioid, tramadol, poses a risk of overdose in both the Near and Middle East and in Africa.
The fourth wave – drug mixtures
According to recent reports, the world is already experiencing the fourth wave of the opioid epidemic – one that is “characterized by polysubstance-involved overdose deaths.” The United Nations Office on Drugs and Crime (UNODC) has warned that “Consumers face increasing risks... from dangerous drug mixtures in retail markets... (and) a growing mix of substances in the drug supply.” According to the CDC, almost 43% of drug overdoses in some US jurisdictions involved both opioids and stimulants in 2022, including mixtures such as “pink cocaine”.
Particularly concerning is the fact that extremely powerful synthetic opioids such as nitazenes (see below) are now commonly being found as adulterants in stimulants and other opioid drugs sold on the street – significantly increasing the chances of overdose while consuming drugs including Xanax and oxycodone, as well as cocaine, heroin and diamorphine.
Nitazenes and other New Psychoactive Substances
According to the European Drug Report 2024, New Psychoactive Substances (NPS) are "a broad range of substances that are not controlled by international drug control conventions,” and in many cases designed specifically to mimic the effects of banned drugs. NPS are also “characterised by the large number of substances that have emerged, with new ones being detected each year”, and can encompass diverse compounds - including synthetic cannabinoids, stimulants, benzodiazepines, hallucinogens, and synthetic opioids.
In 2022, EU member states seized a record 30.7 tonnes of NPS – and by the end of the following year, were monitoring over 950 new compounds, 26 of which were first reported in Europe in 2023. According to the UNODC, the number of NPS identified since 1995 increased to around 1,240 in 2023 – or about four times more than the number of officially controlled substances. This increase in NPS supply is partly attributed to a dramatic reduction in heroin production following the return of the Taliban in Afghanistan, as well as control measures to reduce the availability of fentanyl and its analogues.
The NPS group causing most concern at present is nitazenes – a family of experimental opioid analgesics first developed in the 1950s, but abandoned due to their high potential for overdose and never approved for medical use. Some nitazenes are 800 times more potent than morphine and 40 times stronger than fentanyl – meaning that etonitazene, isotonitazene, clonitazene, and several other nitazene analogues are classed as Schedule I substances by the US Drug Enforcement Administration (DEA). A report by the Organisation of American States (OAS) in September last year suggested that, from the limited data available so far, “nitazene use is a growing trend in North America and... availability is likely spreading across the Americas.” It also noted that nitazene-involved fatal overdoses in Tennessee had increased from 0-42 between 2019 and 2021, while testing also confirmed the presence of nitazenes following more than 60 overdose deaths in Quebec and Toronto between 2020 and 2022.
In Europe, at least 20 European Union (EU) member states have reported the presence of a nitazene, with sixteen different types now identified on the continent, including six out of seven of all new opioids detected in 2023. Nitazene drugs were implicated in 230 deaths throughout the UK between June 2023 and June 2024, as well as deaths or poisonings in Latvia, Estonia, Ireland and France. In Britain, the BBC reported that nitazenes were being advertised on internet platforms such as SoundCloud and X, and posted to the UK from laboratories in China. Meanwhile, in Australia, police seized 742 tablets containing metonitazene that had been posted from the UK – just the third time that nitazenes had been detected in the country.
Graham Biggar, the director general of Britain’s National Crime Agency, warned last year that the hidden presence of potent nitazenes and other synthetic opioids had made taking street drugs more dangerous than ever. “With nitazenes you can absolutely die the very first time you take it, and with nitazenes you very often don’t know you are taking it,” he said. From the other side of the world, Commander Paula Hudson of the Australian Federal Police gave the same grim message: “There is no such thing as a safe dosage when it comes to this drug.”
“Down the road costs” of the opioid epidemic
As well as taking a devastating toll on users and their loved ones, the opioid epidemic has had a powerful negative impact on economies and services around the world. A Council of Economic Advisers’ White House report from 2017 estimated that the direct and indirect costs of the crisis in the US were $504 billion each year – or 2.2% of US Gross Domestic Product (GDP). However, in the so-called “crisis states” – the parts of the US hardest hit by opioids –– the cost may be closer to 15% of GDP. Opioid-related “down-the-road costs” that feed into these calculations include reduced workplace productivity, healthcare (including long-term, expensive substance abuse treatment), plus additional expenses for policing, courts, jails and prisons.
Forensic crime laboratories have also been greatly affected by the opioid crisis – with one study putting the total cost of toxicology and other laboratory work on opioid-related criminal cases at $270 million in the US. The opioid epidemic has already led to higher laboratory charges, longer turnaround times for lab services, and delays to other types of investigations. However, the constant and rapid emergence of new drug threats is also presenting scientists with an additional “myriad of challenges” - not least the adoption of new methods for detection and identification in an age of poly drug use. To assist analytical and research laboratories in their efforts, LGC Standards also offers a dedicated range of quality reference materials and research chemicals for commonly encountered nitazenes – including neats, single solutions, and SILs.
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