2024-11-12 16:39:00
In 25 years, four waves of “epidemics” of deaths due to opioids have occurred in the United States. Depending on the period, they are linked to the overdose of misused medications, heroin or even fentanyl (and derivatives) alone or combined with new synthetic opioids and stimulants. A public health issue that goes beyond the United States alone.
At the origin of a crisis that has been raging for approximately 25 years in North America, opioids have become a major cause of toxic overdose deaths in North America as well as in the European Union (UE).
The death of several world celebrities, including the singer Princehave drawn the attention of the general public to a devastating epidemic which is now even the source of a decline in life expectancy in the United States, according to a study from the Institute for Computational Medicine at Johns Hopkins University. More than 800,000 Americans have died since 1999 as a result of opioid consumption.
Opioids with powerful pain-relieving effects
By “opioid”, we designate any substance, natural or synthetic, that can interact with a family of specific receptors called opioid receptors, expressed on the surface of certain neurons and widely distributed in the brain. Opioids therefore have the main property of being powerful analgesics.
The human body produces its own opioid compounds (dynorphins, enkephalins, endorphins and nociceptins). However, in cases of severe pain, for example after trauma, surgery or metastatic cancer, the effect of these endogenous opioids may prove insufficient to alleviate the painful sensation. It then becomes useful – if not essential – to take an exogenous compound with an opioid action, in order to avoid suffering.
From morphine, a natural opioid, to synthetic products
Since millennialsthe juice of the opium poppy, containing natural opioids such as morphine or codeine, was used as a panacea, notably by the Sumerian and Egyptian civilizations. In the 19th century, the active molecules were extracted, purified and then prescribed to painful patients.
Subsequently, numerous molecules with a structure similar to that of morphine (henceforth called “opiates”) such as heroin or completely synthetic with a structure different from that of morphine (henceforth called “opioids”) such as tramadolthe methadone or the fentanyl were produced in the laboratory.
Mortal risks in case of misuse
Some have retained medical indications and are manufactured and sold by the pharmaceutical industry: these are prescription analgesic opioids. Others have become illicit products, the sale and use of which are prohibited by international conventions. This is the case of heroin which, it must be remembered, was manufactured and marketed in the 19th century as a “heroic” drug.
Unfortunately, all opiates and opioids can be consumed as part of a use disorder, sometimes as recreational products and mostly in connection with the development of an addiction. They can therefore be responsible for a major risk of death. It is this phenomenon that is at the origin of the fatal overdose crisis in North America.
The consumption of opioids causes significant adverse effects (constipation, nausea, drowsiness, urinary retention, etc.) which may be acceptable when suffering from cancer or the consequences of trauma or a surgical intervention. This consumption is, however, not without vital risks, particularly in the event of abuse or misuse.
The misuse of opioids prescribed as medications, like illicit opioids used as drugs, puts one at risk of sudden respiratory arrest (specialists speak of neurorespiratory depression), which depends on the dose consumed.
At the origin of the crisis: a falsely reassuring publication
For almost a quarter of a century, a serious epidemic of deaths secondary to opioid overdoses has raged in North America, and particularly in the United States. In this country, three waves successive deaths have been described since 1999, linked respectively to opioids prescribed as medications (1999-2010), to the heroine (2011-2015), fentanyl (2016-2020). We now mention a fourth wave linked to the combination of fentanyl and illicit stimulants (2020-2024).
Several concomitant phenomena contributed to the occurrence of this crisis. The increase in the use of opioid analgesics at the beginning of the 21st century in the United States was initially the result of excessive and inadequate medical prescriptions favored by erroneous university and post-graduate education of doctors.
Indeed, the broad prescription of these medications was wrongly made reassuring following the publication of an article in the medical journal New England Journal of Medicine explaining the absence of risk of developing dependence in the event of long-term use of an opioid analgesic. It was in fact an observational study published in the form of a letter to the editor, involving a small number of patients, without demonstration value or external validation.
Aggressive marketing and out-of-control prescriptions
This article was then referenced hundreds of times in the medical literature to support this false theory, without additional evidence. Inadequate prescriptions for opioid painkillers then skyrocketed, fueled by aggressive and abusive marketing from one company, Purdue Pharmawho promoted his product based onoxycodone among doctors, pharmacists and patients. This company is now in cessation of activity and its directors accused of causing the deaths of half a million people.
The absence of strict control of medical prescriptions by health authorities was then added as a contributing factor, allowing this phenomenon to develop until 2010, before a decision to withdraw oxycodone from the market by the Purdue Pharma laboratory. not be taken.
This drug had then become the main cause of death from opioid overdose in the United States, the tablets being often pillaged then snorted or injected intravenously by patients who had become addicted following their prescription of long-term opioid analgesic.
Thus, at this period, the prescription of an opioid to a member of one’s own family and, in fact, the availability in the home of this type of product, had become the main risk factor for the occurrence of an overdose, in any no one who has ever received an opioid prescription.
With fentanyl and its derivatives, an acceleration of the crisis
Subsequently and after the withdrawal of Purdue Pharma’s oxycodone from the market and its replacement by a non-pillable delayed release formulation, addicted patients successively turned to the consumption of heroin (produced and brought from Afghanistan) then of fentanyl (produced at lower cost in synthesis laboratories mainly in Mexico, from raw materials imported from China or India).
Powerful structural analogues of fentanyl, initially synthesized as possible drug candidates by the pharmaceutical industry, then became the main opioid sources of deaths and the accelerating death crisis in the United States. Despite a rapid decline in the use of prescription opioids starting in 2010, overdose deaths continued to increase and an acceleration was even observed until 2024.
So, in 2023, around 90,000 deaths have been attributed in the United States to opioid overdoses, and for more than 85% of them, to fentanyl and its derivatives. In 2022, approximately 50 million falsified pills and 4.5 tons of fentanyl powder were seized by US customs authorities, totaling 388 million lethal doses. Enough to kill the entire American population.
From now on, recreational consumption and new synthetic molecules
Today, the recreational use of fentanyl and its derivatives, in combination with stimulant drugs (cocaine et amphetamines) represents the spearhead of the epidemic, among younger consumers and in an essentially festive context.
You should know that fentanyl is 300 times more powerful than morphine and one of its derivatives, carfentanyl, is 10,000 times more powerful than morphine… therefore very toxic.
Various factors have thus contributed to the almost exponential and irremediable progression of the epidemic between 2020 and 2024, including in particular:
the emergence of new very powerful synthetic molecules including fentanyl derivatives but also other types of opioids such as nitazènes,
the development of compounds with a high risk of dependence and rapid acquisition of tolerance,
the combined use of multiple drugs, such as stimulant drugs but also xylazine (“zombie drug”).
Individual vulnerability factors, genetic or non-genetic, also explain the increased risk of death among certain consumers. Finally, the way of life in modern Western society has been questioned by favoring the consumption of increasingly dangerous drugs.
In case of overdose: typical signs for a rapid diagnosis
Neurorespiratory depression following an opioid overdose results in a patient in a typical syndrome associating:
a coma with myorelaxation, that is to say low muscle tone (hypotonia) and an abolition of deep tendon reflexes,
extreme and bilateral contraction of the pupils (tight miosis),
a slowing of the respiratory rate to less than 12/min (bradypnea).
This table is easily identifiable, which allows rapid clinical diagnosis and immediate treatment in the event of an overdose, without the need for additional analyses. If neurorespiratory depression continues, respiratory arrest occurs, followed quickly by cardiac arrest.
Divers additive mechanisms have been proposed to explain the increased risk of sudden death with fentanyl derivatives and in particular the appearance of rigidity of the diaphragm muscle (the “wooden chest wall syndrome”).
Therapeutic treatment is also relatively simple. There naloxone is the only antidote available clinically.
Treatments and avenues of research to limit deaths
A final word to emphasize the importance of strategies to reduce the risk of death from opioid overdose. They are based on the wide use of substitution treatments (in France, methadone and high-dose buprenorphine) and the provision in the community of naloxone known as “take home”, usable by any person, even without medical knowledge, who reportedly witnessed a possible overdose in a known opioid user found unconscious.
Finally, the development of new painkillers and of new opioid formulations devoid of neuro-respiratory toxicity seems promising, but still in the preclinical development phase with uncertain deadlines.
In conclusion, opioid overdoses represent a continuing global public health problem. But hope appeared a few weeks ago with, for the first time in 25 years, a decline in opioid overdose deaths in the United States. A 25th anniversary that is certainly sad… but now, with the hope of a possible resolution of the crisis in sight.
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Of more lethal effects among users, especially when combined with other substances. The synthesis and distribution of these fentanyl derivatives often occur in unregulated environments, leading to variable potency and contamination, which heightens the danger for users.
Community and Policy Response
In response to the escalating crisis, various community and government initiatives have been implemented to combat the opioid epidemic. Strategies have included increasing access to treatment for addiction, enhancing educational programs about the risks of opioid use, and expanding the availability of naloxone, a medication that can reverse opioid overdoses. Communities are encouraged to engage in drug take-back programs to safely dispose of unused medications and reduce the availability of opioids in homes.
Additionally, policy changes at the federal and state levels have aimed to tighten prescription practices and monitoring of opioid prescriptions. Prescription Drug Monitoring Programs (PDMPs) have been established to track prescribing patterns and identify individuals who may be abusing prescription medications. These measures are crucial in preventing misuse and addressing the ongoing challenges posed by opioid addiction and overdose.
The Importance of Public Awareness
Increasing public awareness about the realities of opioid addiction, the signs of overdose, and the importance of seeking help is essential in reducing stigma and encouraging those affected to come forward. Educational outreach can empower individuals and families with vital information on recognizing the signs of addiction and overdose, as well as the steps they can take to seek help or support loved ones struggling with substance use disorders.
As the opioid epidemic continues to evolve, it remains critical for health care providers, communities, and policymakers to work collaboratively in addressing both the immediate needs of individuals affected by opioids and the systemic issues that have contributed to the crisis. Together, these efforts can help pave the way for a healthier future and reduced rates of addiction and overdose across the nation.
