Fentanyl and other synthetic opioids have become a wraith of death and destruction, decimating families and communities, rural and urban alike, at the speed of blight. Synthetic opioids (other than methadone) are now the main driver of drug overdose deaths. Over 80% of opioid overdose deaths are caused by synthetic opioids, and despite government agencies and public officials sounding the alarm, opiate-associated death rates continue to hit successive historical apogee points and break new records, its insatiable bloodlust unslaked by any enormity of human toll.
History and BackgroundFentanyl is a synthetic opioid introduced in the 1960s as an intravenous anesthetic and was specifically engineered to be an ultrapotent compound intended for use after surgery and for the treatment of severe cancer pain. It was synthesized by Dr. Paul Janssen, the founder of Janssen Pharmaceutica, in December 1960. Prior to the synthesis of fentanyl, the two most important opioids were morphine and meperidine. Janssen and his team manipulated the molecular structure of meperidine because it was less complex and more amenable than morphine to tweaking. En route to creating Fentanyl, Janssen created Phenoperidine, which was 25 times more potent than morphine, before finally creating Fentanyl which was 100 to 200 times more potent than morphine.
Mechanistically, fentanyl acts on the mu (µ) opiate receptors in the central nervous system and produces fatigue, sedation, nausea, vomiting, dizziness, respiratory depression (leading to apnea in higher doses), bradycardia and unconsciousness/anesthesia in higher doses irrespective of the mode of administration. Fentanyl is so incredibly potent that its dosage is measured in micrograms as opposed to milligrams ( 1 microgram is 0.001 mg). Fentanyl patches are marketed in 12, 25, 50, 75 and 100 mcg (1000mcg = 1 mg) and the injection contains only 50 mcg per ml of solution.
For additional mind-bending frame of reference, consider that one milligram is about the size of a pinhead, while one microgram is one-thousandth of that pinhead. A dose of 100 mcg (0.1 mg) of fentanyl is equal to 10 mg of Morphine and 75 mg of meperidine. The onset of action of fentanyl is almost immediate when given intravenously with maximal analgesic and respiratory depression occurring after several minutes. However, its ability to produce respiratory depression may outlast the duration of pain relief. Just two milligrams of fentanyl, equal to just 10-15 grains of table salt, is considered a lethal dose.
Staggering StatisticsSince 1999 more than 600,000 people in the USA and Canada have died from opioid overdoses, and a staggering 1.2 million more are estimated to die due to overdose by 2029.
According to the CDC, 107,622 Americans died of drug overdoses in 2021, a 30% year-over-year increase, with 66% of those deaths related to synthetic opioids like fentanyl. Drug poisoning is now the leading killer of Americans between the ages of 18 and 45 and equates to 395 deaths every single day, or 16 deaths every hour from drug overdose, of which 195 were caused by fentanyl.
The major source of street fentanyl is from illicit manufacture and subsequent drug trafficking by Mexican cartels across the southern US border. The intensity of cross-border trafficking has reached an unconceivably high crescendo, producing catastrophic consequences hitherto considered possible only in the dystopian post-apocalyptic realms Hollywood seems fond of churning out from time to time. For example, the state of Colorado seized more fentanyl in the first five months of 2022 than it did in all of 2021.
San Diego is now the national epicenter for Fentanyl trafficking. More deadly fentanyl is being seized by border officials in San Diego and Imperial counties than at any of the nation’s 300-plus ports of entry. In the first nine months of FY 2022 (October through June), U.S. Customs and Border Protection law enforcement agencies in San Diego and Imperial counties (CBP Field Operations and Border Patrol) seized 5,091 pounds of fentanyl – which amounts to about 60 percent of the 8,425 pounds of fentanyl seized around the entire country.
At 2mg lethal dose per person, the 8,425 pounds of fentanyl seized in the first 9 months of this fiscal year is enough to kill 1.9 billion adults. That’s almost twice more than the population of North and South America, combined. In the last week alone 12,000 fentanyl pills disguised as Halloween candy were seized at LAX airport while the NY DEA seized 20 lbs of powdered fentanyl along with 300,000 “rainbow” fentanyl pills. If this is what is being seized, is it even possible to estimate how much contraband lethal neurotoxin is seeping unseized and undetected through our gates, envenomating American society with its deadly payload? Meanwhile the ruling class mindlessly bleats empty platitudes like “one death is too many” or “easily preventable deaths” and watches paralyzed by inaction at a border leaking like a sieve, and dripping with the blood of innocents.
The symphony of destructionIn the United States, fentanyl, like other opioids, is strictly regulated. Although prescription fentanyl overdoses do occur, the vast majority of its deaths are caused by illicit non-pharmaceutical fentanyl manufactured in foreign facilities. Fentanyl is often mixed with heroin or cocaine to increase their euphoric effects, most often without the user’s knowledge. Consequently, most deaths occur due to unintentional overdose. Mexican cartels either source fentanyl from China or, more commonly, manufacture fentanyl for distribution and sale in the United States using precursors imported from China and other countries. The two most common fentanyl precursors are N-Phenethyl-4-piperidinone (NPP) and Anilino-N-phenethylpiperidine (ANPP)
The flow of illicit fentanyl into the US is a carefully orchestrated symphony performed by the strangest of bedfellows: Mexican cartels and Chinese chemical manufacturers. Until 2019, China directly and illegally exported massive quantities of illicit Fentanyl into the US, using shady networks that skirt legal roadblocks by hiding behind shell companies. However, China placed the entire class of fentanyl-type drugs under a controlled regulatory regime in May 2019. Following this scheduling, Chinese traders switched to selling precursor chemicals to Mexican drug cartels. Thus, instead of shipping finished fentanyl to the US, Chinese pharmaceutical precursors now make a pitstop in Mexico where the final manufacturing steps are completed before the final product is trafficked by cartels across the border.
China boasts the world’s largest pharmaceutical and chemical industries and consequently exerts near-hegemonic control over the world’s supply of basic chemical ingredients, pharmaceutical precursors and active pharmaceutical ingredients (API). I have previously written about the national security repercussions of a supply chain for life-saving antibiotics, pharmaceuticals and other infrastructure critical materials outsourced to the US’s greatest foreign adversary. The ongoing supply chain crisis in the wake of the COVID-19 pandemic bears ample testament to the perils of prioritizing profit over manufacturing sovereignty and national security. The U.S. Department of State estimates that more than half of the global suppliers of fentanyl precursors are based in China9. Most drug-manufacturing equipment, such as pill presses, are also produced in China. This equipment is then shipped to places like Mexico and Canada, where criminal cartels use it to manufacture Fentanyl and other synthetic opiates destined for illicit drug trafficking to the US.
Fentanyl is a drug trafficker's wet dream. It is ultrapotent, inexpensive, completely lab synthesized, and reaps landfall returns on investment. A typical user requires less than a milligram for single use and according to a 2016 Wall Street Journal report, producing 25 grams of finished fentanyl costs about $810. However, according to a more recent 2021 PBS investigation, an 11 lb. package of fentanyl sells for only $15,000 in Sinaloa's capital, Culiacan, and probably reflects decreasing costs of production with increasing scale of manufacture. The further the product travels, the more valuable it gets. By the time it arrives in America, 11 pounds sells for upwards of $100,000 Unlike heroin, morphine, or cocaine, its starting materials are not crop-based and prone to the vagaries of mother nature. Thus, insuring a steady supply becomes a matter of human resourcing and international operations management, rather than praying to God for rainfall and freedom from plant disease.
The Sinaloa Cartel and the Jalisco New Generation Cartel (CJNG) are the two main producers and traffickers of fentanyl into America. In a case of life imitating art, the actual process of homebrewing or “cooking” fentanyl is not dissimilar to the TV show Breaking Bad. Cartels set up makeshift labs in the middle of nowhere cow fields to evade law enforcement and other prying eyes. However, unlike Walter White, these farmer-turned-self-taught-cooks have no formal training in chemistry, work without protective equipment and drink beer believing that it possesses mythical properties that protect them from the contact high of being in close proximity to the deadly brew’s fumes wafting atop open flames.
That some cooks die as a result of toxic exposure or inhalation and suffer a fate as gruesome and tragic as those of their victims is probably a grim irony totally lost on them and their brethren. But death is meager disincentive compared to the lure of lucre combined with cartel-engineered destruction of once-thriving agrarian communities served by a justice system dysfunctional enough to allow the powerful to get away with murder, making it the perfect petri dish to incubate the opioid epidemic.
Is there a solution, and the will to implement it?The current opioid crisis is nothing short of cataclysmic and one of the most devastating public health catastrophes of our time. Without urgent intervention, 1.2 million people in the U.S. and Canada will die from opioid overdoses by the end of the decade. As with every inexorable tragedy, there’s danger in allowing the hopelessness of despair to morph into the anesthetized acceptance of the “new normal."
The opioid crisis happened in 3 waves. The first started in the mid-1990s, spurred by FDA-approved OxyContin, which was aggressively promoted to prescribers by Purdue Pharma. This was followed by a second wave, caused by heroin overdoses in already addicted people. We’re currently in the third wave, driven by illegal synthetic opioids like fentanyl. There exists not a simple one-step “flex seal” quick-fix solution to the problem of opiate dependence that has been many decades in the making and inextricably linked to psychological, social and economic factors.
The Stanford-Lancet commission on the north American opioid crisis makes recommendations spanning seven domains– none of which directly relate to stemming the tide of illicit cross-border trafficking, the main reason for the ghastly and alarming increases in death rates. Nevertheless, it includes important recommendations like curtailing pharmaceutical product promotion and decoupling pharmaceutical industry donations to universities and professional associations from control over the content of medical education, closing the pharma-government “revolving door” of employment, limiting pharma political campaign donations and ability to fund “astroturf” advocacy organizations. It recommends increased commitment toward caring for those with substance use disorders, and funding for at-need individuals and populations, as well as pro-innovation policies that prioritize opioid molecule redesign and the development of non-opioid medications.
As well-intended and important as many of these recommendations are, they’re resource and time intensive, their intended impact accrues in a gentle upward slope over time, and some require changing existing laws– an arduous and lengthy undertaking even in circumstances of assured bipartisan support. And while legislative action to increase access to fentanyl test strips is a step in the right direction, expecting individuals in the agonizing throes of withdrawal to test their supply is unrealistic optimism and unlikely to occur with any regularity. In addition, fentanyl analogues like carfentanil (a hundred times more potent than fentanyl), furanyl fentanyl and acetyl fentanyl are even more lethal and potent than fentanyl, evade detection via routine testing, and will eventually replace and outstrip illicit fentanyl for precisely those reasons. The single most important intervention to dramatically reduce unintentional deaths, and buy us time to peel apart the onion layered complexity of opiate addiction (exacerbated by COVID-19 linked isolation, anxiety and lack of access to care) is to dam the flow from the tidal waves of illicit fentanyl crashing on to our borders, and drowning us in a deluge of stupendous neurotoxicity.
The word “terrorist” gets carelessly bandied about these days without so much as even cursory forethought, and yet drug cartels– agents of death and destruction responsible for 9/11 level mortality statistics every 2 weeks– are not even designated as terrorist organizations. They are not accorded the same intensity of media focus, law enforcement resourcing and objectively quantifiable actions beholden to public scrutiny that comes with that label. Much like the anthropomorphizing of guns used by gun control fetishists, we hear only about the drug, but rarely about how it got here. Border security is synonymous with national security, but it is high time we associated it with the life and death consequences reverberating through the nation and impacting generations to come, and demand that public officials treat it as such.
China has become the world’s pharmacy, not only for therapeutic medicines, but also recreational drugs, and encouraging hopeless addiction to his product is every good drug dealer’s business model. While the Chinese government has made all forms of fentanyl illegal since May 2019, it did not ban all precursor chemicals that can be used to make fentanyl. Since then, at least four substitutes for two main fentanyl precursors have become increasingly common on the clear web. These precursor substitutes were “masked" chemicals, which are chemically altered to escape detection and can easily be transformed into a controlled fentanyl precursor through simple chemical reactions. For example, although the two main fentanyl precursors, NPP and ANPP, are controlled, the illicit trade network was able to switch to marketing non-scheduled precursor chemicals. Mexico’s seizure of nearly 70 kg of 4-AP, a non-scheduled precursor of ANPP, mislabeled as washing powder, and Belgium’s seizure of about 1 kg of 4,4-piperidinediol, another alternative precursor of fentanyl, both of which allegedly originated from China, show how easily these regulatory safeguards can be skirted and circumvented.
The rise of these precursor substitutes owes to the fact that China is the world’s main supplier of a diverse array of chemicals, drug precursors and finished drugs, and this enables Chinese manufacturers the ability to shift from illegal to legal chemical production very quickly in order to circumvent legal roadblocks.
We’ve become victims to the self-inflicted wound of a manufacturing base enfeebled in favor of outsourcing the most vital parts of our economy in monomaniacal pursuit of record profits, and no amount of political pressure can convince those who dominate us to cease their withering depredation. Reshoring our manufacturing sovereignty and facilitating a manufacturing renaissance is vital not only from an economic perspective but augurs our very survival from whatever next inevitable scourge awaits us. If we can’t get clean and sober from our fatal addiction, we’re consigned to the eternal doom of pawning our freedom, liberty, and the future of our children in exchange for our drug fix.