Oxycontin to Heroin: The First Two Waves,

1995-2017

Opioid Era in America—our new Gilded Age, where companies dispensed with any moral or ethical concern in the pursuit of making money. 

Sam Quinones[1]

Serotonin and dopamine are neurotransmitters, chemical messengers, sent from the body’s neurons to cells and muscles related to bodily functions. Serotonin is essential for regulating emotions. When one’s levels of serotonin are properly balanced, their mood and sense of well-being are more stable. Dopamine, on the other hand, is a neurotransmitter that is responsible for how one experiences pleasure. When one does something enjoyable, the dopamine release tells their brain that this feels good, motivating one to repeat that activity. Healthy dopamine levels can enhance one’s motivation and ability to concentrate. Thus, while serotonin inhibits many forms of impulsive behavior, dopamine enhances it.[2] Human brains have evolved to keep serotonin and dopamine in balance naturally. Dopamine tells us that something better awaits us; serotonin says we have had enough.

Morphine, heroin, opium derivatives, and synthetically opioids, like fentanyl, when introduced to the body, increase dopamine while reducing serotonin. Desire overwhelms moderation and contentment. Furthermore, “dopamine levels don’t diminish when a person uses a drug of abuse. They stay and prod the person to consume more. When the drug is removed, the dopamine plummets far below normal levels, leaving one frantically wanting more. This is part of how cravings are created.”[3] 

The body produces opioids naturally but not enough to stop severe or chronic pain. When prescribed and used properly, opiates can mitigate pain, allowing patients to feel and function normally.[4] Opiates are commonly used to treat patients in severe pain from cancer treatment or major surgery. One opiate narcotic painkiller often prescribed by doctors is Oxycodone, which has an immediate painkiller effect when taken. Another painkiller, Oxycontin, was developed in 1995 for those suffering from mild to moderate pain and needing pain relief for a longer period. Oxycontin has a much stronger effect on pain because it has a high concentration of Oxycodone. Medications that have Oxycodone added can relieve pain for between four to six hours, while Oxycontin can relieve pain for about 12 hours.[5] 

The First Wave: Purdue Pharma

The addictiveness of opiates dictated a long-standing prescription practice administered by specialists. This practice changed in 1996 when Purdue Pharma introduced a controlled-release version of Oxycontin designed to be less addictive than the instant-release version but equally as effective in relieving pain. This claim became a huge selling point of Purdue Pharma’s advertising campaign of Oxycontin—an advertising campaign that led to a sharp increase in the rate of opioid prescriptions.

From 1996 to 2002, Purdue Pharma’s annual sales of Oxycontin increased from $44.7 million to $1.5 billion (U.S. General Accounting Office Report – Oxycontin).  To increase its marketing reach to physicians, Purdue doubled the size of its prescription sales division, creating a division specifically focused on doctors that operated out of hospitals. In 1996, its 300-person sales team had a call list ranging from 33,400 to 44,500 doctors. By 2001, the sales team had grown to 700 representatives with a call list ranging from 70,500 to 94,000 doctors.[6]

As Purdue Pharma began its advertising campaign, the firm began to make greater use of prescriber profiles. For Purdue Pharma, the use of prescriber profiles and its increased sales force helped dramatically expand the marketing of Oxycontin. Purdue also hosted numerous physician symposiums focused on pain management and the effectiveness of Oxycontin. As noted, Purdue’s marketing strategy of Oxycontin was a success. Prescriptions for Oxycontin from primary care physicians was Purdue’s leading source of sales from 1996 to 2002.

The global management and consulting firm McKinsey and Company recommended to Purdue Pharma a plan that Purdue referred to as “Evolve to Excellence” (E2E), which aimed at urging doctors to prescribe the pill at higher doses. With McKinsey, Purdue developed the FieldGuide software that allowed the company to target high-prescribing doctors. In a review of thousands of internal McKinsey documents, the New York Times found that the firm repeatedly allowed employees who served pharmaceutical companies, including opioid makers, to also consult for the US Food and Drug Administration (FDA)—the drug industry’s primary government regulator. New York Representative Carolyn Maloney, commented that “at the same time the FDA was relying on McKinsey’s advice to ensure drug safety and protect American lives, the firm was also being paid by the very companies fueling the deadly opioid epidemic to help them avoid tougher regulation of these dangerous drugs.”[7]

Unfortunately, problems with Oxycontin abuse began surfacing in 2000 when there was an increase in the number of reports of patients visiting several doctors in hopes of receiving one or multiple prescriptions. In 2002, Oxycontin was cited as one of the leading causes of admittance to rehabilitation clinics in several Appalachian states. The rise in OxyContin abuse, in turn, led to a congressional hearing in 2001 in which officials from Kentucky, Virginia, and West Virginia testified to lawmakers about Oxycontin abuse in their states. In 2003, the United States General Accounting Office (GAO) released a report in which it recommended a new FDA label for Oxycontin and the development of a risk-management plan to lower the abuse of Oxycontin along with a national response to deal with Oxycontin abuse going forward.

By 2010, national awareness of the problems associated with overprescribing opioids — what would later be described as the “first wave of the opioid crisis’’— was growing and led other states to crack down on the clinics operating in their jurisdictions. Along with the closing of pain clinics, state and local law enforcement agencies implemented stricter monitoring methods to track the prescriptions of painkillers and began suspending the medical licenses of doctors found guilty of inappropriate prescriptions. In Ohio, for example, the Governor’s Cabinet Opiate Action Team (GCOAT) was launched in 2011 to combat the state’s prescription opioid abuse. In May of 2011, the governor also signed Ohio House Bill 93, which placed tighter controls and limitations on physicians prescribing opioids. (In 2011, 27 of 136 physicians were targeted in Ohio for inappropriate prescriptions or lenient pain clinic operations.)[8]

In 2004, the West Virginia Attorney General sued Purdue for reimbursement for excessive prescription costs. West Virginia was followed by Kentucky in 2007 when their Attorney General sued Purdue over widespread oxycontin abuse in Appalachia. By January 2019, 36 states had filed suits against Purdue Pharma. Finally, in October 2020, Purdue agreed to an $8 billion settlement, pleaded guilty to three criminal charges, and agreed to reorganize as a public benefit company under a trust that is required to consider American public health.

In 2021, nationwide settlements were reached to resolve all opioid litigation against the three largest pharmaceutical distributors—McKesson, Cardinal Health, and AmerisourceBergen—and against Janssen Pharmaceuticals, Inc. and its parent company Johnson & Johnson. The settlement calls for the distributors to pay up to $21 billion over 18 years, and for Johnson & Johnson to pay an additional $5 billion. In 2022, settlement agreements were announced with three pharmacy chains—CVS, Walgreens, and Walmart—and manufacturers, Allergan and Teva. Teva agreed to pay up to $3.34 billion over 13 years and to provide $1.2 billion of its generic version of the drug Narcan over 10 years; Allergan agreed to pay up to $2.02 billion over seven years, CVS $4.90 billion over 10 years, Walgreens $5.52 billion over 15 years, and Walmart $2.74 billion in 2023.[9] [10] In a 2023 settlement, Kroger agreed to pay up to $1.2 billion to states and subdivisions and $36 million to Native Americans.[11] Finally, McKinsey agree to pay approximately $870 million to resolve lawsuits by hundreds of US local governments, school districts, and state Attorneys General.[12]  

The Second Wave: Heroin

By all accounts, the concerted efforts in Ohio, Kentucky, Florida, and other states were effective in reversing the increasing trend in prescription-drug overdose. In Ohio, for example, prescription opiates decreased from 45% of all unintentional drug overdoses in 2011 to 22% in 2015. The number of prescriptions for opiates and patients receiving opiates also dropped significantly from 2012 to 2015.

The decline of opioid availability left the large number of people who had developed a prescription-opiate addiction with few options. Many addicts began buying heroin. Narcotics traffickers and drug cartels realized that an illicit market for opioids had already been created and, with demand in place, saw the opportunity to profit from distributing this horrendous substitute. Many people addicted to prescription opiates discovered that they experience a very similar high from using heroin. A 2016 intelligence study by the Drug Enforcement Administration (DEA) reports that nationwide heroin-related deaths more than tripled from 2010 to 2014. In Ohio, the proportion of drug overdoses due to heroin surpassed prescription opiates, and heroin accounted for over 45% of all the unintentional drug overdose deaths from 2013 to 2015.

Unfortunately, while the closing of pill mills, the suspension of medical licenses for inappropriate prescriptions, and state and county suits and judgements against Purdue Pharma reversed the prescription opiate epidemic, it did not stop the increases in the number of opiate overdoses. The rise in heroin death following the prescription crisis led to the “second wave of opioid crisis.”

Fentanyl and Super Meth:

The Third and Fourth Waves

Fentanyl 

“The Mexican drug cartels, hardening and seemingly indifferent to human suffering, have a fearful respect for fentanyl, they called it El Diablo, “The Devil.”  Peter Schweizer[13] 

After declining 4.1% from 2017 to 2018, the Centers for Disease Control and Prevention (CDC) reported an 18% increase in the number of overdose deaths for the preceding 12 months ending in May 2020, with 25 states reporting increases over 20%. West Virginia saw a 32% increase in overdose deaths for that time period compared to the previous year. In Kentucky, deaths climbed by 27% and in Ohio by 16%. Overall, the CDC reported 81,230 drug overdose deaths occurred in the United States in the 12 months ending in May 2020, the largest number of drug overdoses for a 12-month period ever recorded. The CDC report, in turn, identified synthetic opioids linked to illicitly manufactured fentanyl as the primary cause for the increases in overdose deaths. The Ohio Addiction & Recovery Center reported that fentanyl was involved in about 80% of all heroin-related overdose deaths in 2018, 74% of all cocaine-related overdose deaths, and 67% of all methamphetamine-related overdose deaths.[14] 

Origin of Fentanyl 

The structures of different opioids share many similarities. Whereas opioids like codeine, oxycodone, and hydromorphone are synthesized by modifying morphine, fentanyl is synthesized by modifying meperidine—a synthetic opioid.[15]  Fentanyl was developed in Belgium in 1959 by Dr. Paul Janssen under a patent held by his company, Janssen Pharmaceutical. In 1961, Janssen Pharmaceutical was acquired by Johnson & Johnson.  A

hundred times stronger then morphine, the medical profession quickly adopted fentanyl as an effective pain reliever and anesthetic. The FDA approved fentanyl for legal, prescribed use in 1968. The agent was introduced as an anesthetic under the brand name Sublimaze. Prior to fentanyl’s introduction in the late 1960s, anesthesiologists used flammable gas. With fentanyl, patients could now be conscious during surgery, with blood pressure normal. Fentanyl was short-acting and could be reversed quickly with naloxone. People were in and out of it, without lingering aftereffects.  By the mid-1990s, the fentanyl patch was developed to manage the chronic pain of cancer patients.[16]  

In addition to the Janssen method for synthesizing fentanyl, there are also the Siegfried and Gupta synthesizing methods. The Siegfried method is a simpler technique, requiring five chemical steps compared to Janssen’s seven.  The Siegfried formula was first published in the 1990s on the Internet. Starting in 2000, underground chemists began to discover the method, as well as fentanyl’s potency and similarity to heroin. For a time, it would become the leading method to illegally produce fentanyl in both U.S. and foreign secretive laboratories.

The Gupta method requires only two steps to creates fentanyl’s precursor. Fentanyl created using the Gupta method requires only one single vessel, leading to its nickname, the “one-pot method.” The Gupta method is often used by clandestine chemists, often referred to simply as “cooks,” to convert precursors into ANPP, before using that to make fentanyl; or simply getting their hands on ANPP and converting that into fentanyl. The Gupta method is currently considered the most widely used method to produce illicit fentanyl, according to samples analyzed by the DEA’s Fentanyl Profiling Program.[17]

A fentanyl high is similar to that of heroin, but with a shorter duration, making it more addictive. As noted, fentanyl is nearly a hundred times more potent that heroin. Fentanyl can also be smoked, snorted, or injected. Moreover, unlike poppy-derived opiates, fentanyl is cheap to produce since it is entirely synthetic and can be clandestinely manufactured—it requires no farming, cultivation, sunlight, or irrigation. According to a 2019 DEA report, it is "estimated that each fentanyl pill costs only $1.00 to produce and can be resold in the U.S. for at least 10 times as much.”[18]

The Chinese Connection

“Doctors and Big Pharma prepared the battlefield …creating a market for the cartels, who then jumped at the opportunity to own the supply and feed the demand”

Sam Quinones[19]

Since the early 1980s, Chinese triads have controlled 60% of the heroin smuggled into the U.S. Sam Gor, a major international crime syndicate known as ‘The Company,’ controls between 40% and 70% of the Asia-Pacific methamphetamine market, while also trafficking in heroin, synthetic drugs, and precursor chemicals. The syndicate consists of five different triads: 14K, Bamboo Union, Big Circle Boys, Sun Yee On, and Wo Shing Wo. Its most active triads involved in the heroin trade are the 14K and the Big Circle Gang.[20]  Since the 1980s, Chinese officials have allowed the triads and triad-linked businesses to operate. The triads have long been alleged to have connections to the Chinese Communist Party (CCP), often through the CCP’s united front groups. In return for allowing their operation, triad members allegedly help the party by suppressing dissents and protests.[21] [22]

When the Janssen patent expired in 1981, fentanyl production and distribution on the black market accelerated. In 1985 Janssen Pharmaceutical (J&J) opened its first Western pharmaceutical factory in China. Janssen’s China venture marked the time when Chinese cartels began to make fentanyl. The street names for fentanyl were “China Girl” or “China White.” Following the first wave of the opioid crisis spurred by the pharmaceuticals, Chinese triad-drug traffickers discovered fentanyl as a new way to profit. It could be produced synthetically, laced with pills and other substances, and distributed in different modes to an already existing network of traffickers and dealers (see Exhibit 1). It could also be sold via the internet. As Peter Schweizer describes in his book, Blood Money:

The low cost of fentanyl also created a myriad of international drug enterprises, many in China, but also in India and the Middle East, that manufactured fentanyl, its analogues, and other synthetic drugs. Many of these operations advertised on the public and dark websites and through encrypted applications like WhatsApp, WeChat, and Wickr. They also distributed their fentanyl, precursors, and other drugs through common air and ground carriers, such as UPS and FedEx, carefully packaged to deceive customs inspectors in places across the U.S. and other countries. In the case of fentanyl, drug dealers would mix the fentanyl they acquire from the cartel network or clandestine drug enterprises with other drugs to make them stronger or to improve low quality drugs. The chemicals were paid for in MoneyGram, Paypal, Alibaba, bank transfers, and most commonly Bitcoin and other cryptocurrencies, which make it difficult for enforcement authorities to follow the money.

In 2006, mixtures of fentanyl with cocaine, heroin, marijuana, and pills caused the first major outbreak of deaths in cities across the U.S. To be handled and sold to users, fentanyl was typically packaged with larger quantities of other powders. Local dealers, in turn, had to mix the powders. It took only a small amount of fentanyl’s potency to get someone high and only a minute amount more to kill someone—the difference was the equivalent of a few grains of salt. To mix the powders, dealers in the beginning of the fentanyl epidemic often used the magic bullet blender. As Sam Quinones notes, “Nothing in the Magic Bullet infomercial, of course, suggests that the Magic Bullet ought to be used to mix synthetic narcotics. Yet that’s just what happened. The tiny dynamo proved an especially poor blender of highly potent fentanyl, contributing to epidemic of fentanyl deaths.”[24]  

Exhibit 1: Gordon Jing Gordon Jing was the online moniker of a father, Guanghua Zheng, and son, Fujing Zheng, who ran a major international drug enterprise based in Shanghai. They manufactured and sent kilograms of fentanyl, its analogues, and other synthetic drugs through the mail to two dozen countries and at least thirty-five American states.     Videos: ·      60 MINUTES: Deadly fentanyl bought online from China being shipped through the mail ·      Two Chinese nationals charged with operating global opioid and drug manufacturing conspiracy resulting in deaths in Akron

In the late 2000s and 2010s, many people quickly were attracted to vaping as a less harmful alternative to tobacco and as a possible pathway to eliminating tobacco addition. The product was marketed   as being less harmful than regular tobacco cigarettes, even though vapes still contain nicotine and nearly 2,000 chemicals—the vast majority of which are unidentifiable. The National Youth Tobacco Survey in 2021 found that two million young people use e-cigarettes. This survey also found that 28% of high school students and 8% of middle school students currently vaped on a daily basis.[25] The significant rise in the popularity of vaping also coincided with the rise in fentanyl-laced vapes, compounding the danger of synthetic drugs. Fox 35 in Orlando, FL reported that in one Florida high school, a student's vape tested positive for fentanyl. Perhaps, the scariest part of the report, though, is that the student was unaware of fentanyl and it dangers. Unfortunately, there were many other overdose victims who also unknowingly smoked vape laced with the fentanyl who were not as fortunate.[26]  

The flood of fentanyl distributed through the mail from China launched the first fentanyl crisis. Fentanyl distribution by parcel services, however, was limited.  The Chinese cartels found a more economical solution to shipping fentanyl incrementally through the mail by producing it in Mexico, often through clandestine partnerships with the Mexican Cartels. According to Schweizer:

The Sinaloa Cartel is the largest drug trafficking organization in the world. According to the US Attorney General, from 1990 to 2008, this Cartel was responsible for importing and distributing 200 tons of cocaine and heroin in the U.S.  In 2010, the Cartel also discovered the market opportunity for fentanyl by purchasing fentanyl precursors from the Chinese triads to produce fentanyl and then smuggle it north through its network of dealers. The second most powerful drug cartel in Mexico is the Jalisco New Generation Cartel (CJNG). This cartel is believed to have over 100 meth labs throughout the country and generate over $14 billion per year.[28] The Mexican government consider CJNG to be the most dangerous criminal organization in Mexico. From 2018 to 2020, the Armed Conflict Location & Event Data Project reported that CJNG engaged in 298 acts of gang-related violence, more than any other cartel during that period. [29] By 2020, U.S. counter-drug officials considered CJNG its biggest criminal drug threat, and Mexico's former security commissioner called the group "the most urgent threat to Mexico's national security".[30] 

In May 2019, China's government banned the production and sale of fentanyl and many of its variants. According to a National Public Radio (NPR) investigation, to circumvent this ban, Chinese vendors began marketing fentanyl analogues and the precursor chemicals used to make fentanyl, shipping them directly to customers in the U.S. and Europe, as well as to the Mexican cartels. The analogues are compounds that are only a few chemical steps away from fentanyl. Synthetic opioid vendors shield themselves behind China’s legitimate pharmaceuticals sector.[31]  Infobae, a Mexican media outlet, identified sixty-four Chinese companies that were major suppliers to the Sinaloa Cartel and CJNG in Mexico.[32]  Moreover, 90% of the fentanyl precursors and analogues produced in China are shipped to international terminals in Manzanillo, Mexico.[33] The ports are owned and operated by Hutchison Holdings, which is largely owned by the triad-linked tycoon Li Ka-shing. Hutchison also owns the railroad terminals that transport goods to Central Mexico.[34] The northern regions of Baja California, Sinaloa, and Sonora have been named the ‘Golden Triangle’ for fentanyl production and transferring. The region distributes fentanyl as raw fentanyl powder and counterfeit pills pressed with fentanyl and by trafficking cocaine, heroin, meth, and marijuana cut with fentanyl.  San Diego and Arizona are currently major conduits for fentanyl trafficking in the U.S.[35]

Fentanyl pressed into phony pills also opened the American pill market to other underground drug enterprises. Chinese companies, in turn, smuggle pill presses or their parts illegally into the United States and Europe to drug dealers and criminal gangs.  They also sell pill presses and parts to Mexico, including the metal cast dies to imprint pills with counterfeit numbers with the markings of real oxycodone pills. The pills, in turn, increased the likelihood that people would die who simply obtained a pill from a friend. Across the country, young people started dying from pills they thought were legitimate. According to the DEA:

In July of 2023, the United States House of Representatives passed legislation sponsored by Kentucky Congressman Andy Barr to hold Chinese opioid manufacturers accountable. “The Stop Chinese Fentanyl Act” modifies the earlier approved Fentanyl Sanctions Act by allowing Chinese entities to be sanctioned as foreign opioid traffickers if they are involved in the production, sale, financing, or transportation of synthetic opioids or their precursors but do not take sufficient actions to prevent opioid trafficking. This includes cooperating with US counter-narcotics efforts and implementing know-your-customer procedures. This legislation also permits the imposition of sanctions on Chinese officials who have significant regulatory or law enforcement responsibilities over such entities if they fail to take credible steps to combat opioid trafficking.[37] It should be noted that efforts trying to stop Chinese exports of fentanyl ingredients are hindered by ever-evolving new recipes for the drug and ever-adapting supply chains, with India becoming the latest source of chemical precursors.

With its addiction potency, low cost, and increased availability, drug users began using pills, cocaine, heroin, meth, and marijuana cut with fentanyl and soon became straight-up fentanyl addicts. As Sam Quinones writes:

Synthetic Methamphetamine—P2P

Super Meth 

Meth was originally developed as a stimulant for narcolepsy and asthma but as time went on mainstream use made it famous for its party use. Old meth had low purity, was extremely hard to make, and was quite costly. This all changed when an old German recipe was rediscovered by drug cartels in South America. Rather than using the rare, ephedrine as the main ingredient for meth, the new formula called for more easily available substances like sulfuric acid, hydrochloric acid, or racing fuel. With this new formula making ingredients easily available, the cartels lowered the price of the meth by 71%, and their purity, in return, went up to 97%. This revolution in methamphetamine made it far more accessible for all users at all price points. History of Meth[39]

In 1893, methamphetamine (meth) was synthesized from ephedrine, a natural substance from the ephedra plant, by a Japanese chemist. Meth was used as a stimulant and appetite suppressant. In 1938, meth was marketed on an industrial scale in Germany under the brand name Pervitin.  It was used by the Third Reich for its stimulant effects and to induce extended wakefulness. However, the withdrawal symptoms were found to be so serious that the army had to be cut back on its usage. In the 1950s, meth was used in the U.S. to create the diet drug, Obetrol. However, because of its addictive properties, the governments had to regulate its production. In the United States, methamphetamine hydrochloride, under the trade name Desoxyn, has been approved by the FDA for treating attention-deficit/hyperactivity disorder (ADHD) and obesity. The production, distribution, sale, and possession of meth is highly restricted or illegal in many countries. With high doses, meth can cause psychosis, seizures, bleeding in the brain, paranoia, hallucinations, delirium, delusions, and violent behavior. Recreational use can lead to mood swings and increase sexual desire. Meth addicts can also lose their teeth quickly, a condition informally known as meth mouth.[40] 

The Sam Gor syndicate controls a large portion of the illegal Asia-Pacific meth market with distribution to the U.S. The Mexican cartels, in turn, distribute Asian meth to the United States, as well as produce it. California biker gangs have also been part of the illegal meth trade in the US. Until 2006, most of their meth labs used the ephedrine method to create meth.[41] See Exhibit 2.

In 2006, the U.S. passed drug laws requiring ephedrine and pseudoephedrine to be behind pharmacy counters. The meth cartels, in turn, began to reinvent their processes. This gave rise to the birth of phenyl-2-propanone, or P2P, methamphetamine, also called super meth. As Sam Quinones writes:

Exhibit 2: Ye Gon   In 2007, Ye Gon was indicted in the United States District Court for the District of Columbia on conspiracy to aid and abet manufacture methamphetamine. He was considered a pioneer in the massive production of methamphetamines. In 2007, the Mexican government entered Ye Gon's home and seized $207 million in cash—the largest cash seizure in Mexican history.   Meth Trafficker Sentence Highlights Asia Ties to Mexico’s Sinaloa Cartel

Traffickers began to employ organic chemists who had access to the chemistry literature and possessed the skills to improvise new ways to make the ingredients. Soon a large number of cheaper ways to make P2P appeared on the dark web. The chemicals that could be used to make P2P were quite toxic but available and used in many industries.[43]  As Quinones further notes: “Country’s law enforcement could not clamp down on supplies of these chemicals the way it had with ephedrine, not without damaging legitimate sectors of the economy.”[44] The spread of the knowledge on how to make P2P along with the easy access to world chemical markets transformed the meth industry from an oligopolistic market comprised of a few large cartel-controlled operations with large labs and storage facilities to a competitive market comprised of hundreds of smaller, well-run operations, as well as the large cartel syndicates such as Sam Gor, Sinaloa, and CJNG.  Competition among small and large producers drove meth purity to record highs and caused meth prices to plummet. A pound of meth fell below $1,000 for the first time on US streets—a 90% drop from a decade earlier.

As prices dropped and production increased, super meth began appearing everywhere. Meth became a fentanyl substitute, with many addicts believing that unlike fentanyl, meth didn’t kill you.”  As Sam Quinones continues:

Illegal ephedrine-based meth was thought of as a “party drug,” creating euphoric and energizing highs that lasted around 12 hours. With fewer doses than ephedrine-based meth, super meth instead created a stupefying high, leaving users incapacitated for 24 hours or more. P2P also damaged organs, decreased brain functions, and often lead to death, especially when laced with fentanyl. Throughout this change from old meth to P2P meth, people have documented their journeys.[46] On Bluelight.org, a forum for drug users, community member Raysu explains the difference based on their personal experiences saying: “Whatever is coming up in the southwest out of Mexico is something else. I had different sources. It always ‘tasted’ a bit off regardless and some were all side effects and no rush/minimal high. Also, I never experienced paranoia until then— epic-level paranoia.” This mirrors what Sam Quinones said in his The Least of Us, that P2P meth causes people to use the drugs more often to maintain the high. Mr. Quinones also says that one of the worst parts about P2P is the paranoia that it causes. It rips people away from the community, causes them to reject everything, and eventually lands them on the streets with nowhere to turn.[47] The change from old meth to P2P meth has been especially disconcerting because of the ease of access and the necessity to use more and more, which is eerily similar to the fentanyl crisis. P2P now makes up 91% of the meth used in America according to the DEA.[48] 

The Fourth Wave

More than a million people have died since 1999 from a drug overdose. According to Centers for Disease Control, drug overdose deaths in the U.S. exceeded 100,000 in 2021 and then increased in 2022 and 2023, with synthetic opioids being the main driver (88%).  Following the first opioid wave with prescription drugs, the second with heroin, and the third with fentanyl, Millennium Health labeled this recent epidemic with meth laced with fentanyl the fourth wave.[49]

Perhaps the most disconcerting problem associated with the new synthetic drugs is that they can be mixed with other drugs and be used unknowingly. During previous drug epidemics, most users were fully aware of what drugs they were using. With fentanyl and P2P meth, on the other hand, drug users are often completely unaware of the substances they are putting into their bodies.[50] In a recent study, Millennium Heath reported on an increase in overdose deaths resulting from meth, and to lesser extend cocaine, that were laced with fentanyl. Analyzing urine drug tests from over four million samples, they found that over 93% of the samples that tested positive for fentanyl had another substance, with meth being detected in 70% of the fentanyl-positive urine samples in the Pacific and Mountain West states and 50% in the mid-west and southern states. The study concluded that fentanyl was increasingly being used in conjunction with meth.[51] 

The CDC estimates about 33,800 meth-related fatal overdoses involving drugs in the methamphetamine category over a one-year period from October 2021 to October 2022. In their Methamphetamine Plan Implementation Report, the CDC states that “This statistic reflects a significant increase over the past several years. According to toxicological reporting, more than 60 percent of persons whose cause of death involved methamphetamine use were also found with fentanyl analogues or other additives.[52] In a 2023 UCLA study, researchers similarly found that the proportion of US overdose deaths involving both fentanyl and stimulants (such as meth) has increased more than 50-fold since 2010, from 0.6% (235 deaths) in 2010 to 32.3% (34,429 deaths) in 2021. The study also declared that “this rise in fentanyl/stimulant fatalities constitutes the ‘fourth wave’ in the US’s long-running opioid overdose crisis—the death toll of which continues to rise precipitously.”[53] 

Another dimension of this fourth wave is the emergence of a new group of synthetic drugs even more powerful than fentanyl—nitazenes, xylazine, rorphine, and carfentanil. Nitazenes is a specific subclass of opioids that works on a particular opioid receptor. Nitazenes includes isotonitazene, metonitazene, and etonitazene. According to US News and World Report, some forms of nitazenes are 40 times more potent than fentanyl. In August 2018, nitazenes was found in dozens of corpses in Chicago and Milwaukee, and from there it spread to Michigan, Indiana, and Tennessee, killing at least 230 people. Since 2019, US News and World Report reported that between 1,000 and 2,000 deaths are associated with nitazenes across the entire U.S.[54] Researchers believe it may be marketed by Chinese chemical labs as a replacement for fentanyl.  In April 2020, nitazenes seemed to fade, only to be replaced by brorphine, which showed up in the corpses of 130 people in many of the same states.[55] 

More potent than nitazenes is carfentanil, an opioid used in veterinary medicine. In 2018, there were 174 overdoses from a batch of heroin found in Greater Cincinnati. Doctors were dumbfounded when they found traces of carfentanil in the body. Carfentanil is an elephant tranquilizer that can be up to 100 times stronger than fentanyl, which is 50 to 100 times stronger than heroin.[56] Carfentanil has been found cut or mixed into street drugs like heroin, illegally manufactured pills, crystal meth, cocaine, or crack and, according to DEA, has been fueling the overdose epidemic in the U.S.

Commentary: Fentanyl and Say’s Law How Never-Ending Supply Creates Lethal Demand Emily Branca and Seth Workman   Known as the “French Adam Smith,” Jean-Baptiste Say (1767-1832) was a supporter of Adam Smith’s economic system of natural liberties, competition, and limited government. A strong advocate of laissez-faire, his Treatise on Political Economy was the principal economic textbook in the U.S and Europe during the first half of the 19th century. His text was the first to introduce utility as a factor in determining demand, the importance of the entrepreneur, and an economic methodology based on inductive logic. Say’s most enduring contribution, though, is his doctrine known as Say’s Law: “supply creates its own demand.”  To Say, production is the cause of consumption: Say’s law really states that the supply of X creates the demand for Y. Today, when a profitable business moves into an area, it creates jobs and demand for goods and services. The increased consumption is derived from the new supply—the new business.[57] However, what happens when the good is an addicting drug; a good that is characterized by increasing marginal utility, where the utility from consuming the good increases at an increasing rate as one consumes more of the good. The notable economist, Irving Fisher, was the first to point out that goods characterized by increasing marginal utility lead to a “corner solution” in which the good disproportionally dominates the consumer’s spending, and as a result adversely impacts the overall economy. When examined within the context of the fentanyl epidemic, Say's Law highlights the insidious nature of addiction; that its production drives an immediate and insatiable demand.  The consumption of fentanyl activates the ticking of a biological timer that increases its consumption, leading to a cycle of increased production, enhanced addiction, greater increase in demand, and greater increase in production.[58]

Finally, xylazine is a powerful tranquilizer used by veterinarians, like carfentanil, to sedate dogs, cats, and horses. On the streets, it is mixed with heroin, fentanyl, and cocaine and is referred to as tranq or tranq dope.  Adding tranq, in turn, serves to enhance the effect of these drugs and to prolong the fentanyl high.  The FDA reports that tranq is now found in up to 15% of fentanyl tests.[59] Reports by users of tranq-enhanced fentanyl describe lapsing into hour-long blackouts followed by an intense urge for more of the drug.[60] A 2022 report published in Drug and Alcohol Dependence, estimated that tranq’s presence in drug-related deaths rose from 0.3% to 6.7% between 2015 and 2020, with proportions found to be more than 10% in Connecticut, 19% in Maryland, and nearly 26% in Pennsylvania.[61]

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