Missouri’s Fentanyl Problem: The China Connection

Abstract

Recently, Missouri has followed an overall upward trend in opioid overdose deaths. In 2018, Missouri was the state with the largest absolute and percentage increase in opioid-related overdose fatality rates per capita over the previous year (18.3% and 3.1/100,000). This increase occurred despite an overall decrease in U.S. opioid-related death rates in the same period. This report identifies illicitly manufactured fentanyl (IMF) (and analogues) as the drug most responsible for this rise in opioid deaths in Missouri, with stimulant overdoses (primarily from methamphetamine) in second place.

Within Missouri, we find the areas where opioid deaths are highest: St. Louis and the city’s fringe areas, following the national trend for high rates in fringe areas. Based on reports from CDC Wonder data, county medical examiners, law enforcement agencies, and drug addiction prevention agencies, we conclude that IMF and related synthetic opioids arriving from China are primarily responsible for fatal narcotic overdoses in Missouri. Despite the COVID-19 disruption of fentanyl manufacturing and distribution centers in and around Wuhan, China early in the pandemic, preliminary 2020 data from medical examiners’ offices show an upswing in opioid deaths, an indicator that Chinese fentanyl producers have restored the supply chain.

Missourians are Dying of Fentanyl Overdoses

Case Report 1, March 2020

The 25-year-old man was found dead in a motel in St. James, Missouri, still wearing pajamas and a hospital armband from his stay at Phelps Health Hospital, where he left against medical advice. Drug paraphernalia found in the room included a heroin cooking apparatus: an upside-down Coke can with a cutout in the side to insert his butane lighter, which he favored over cooking with a spoon. His prescription bottle of alprazolam had only two tablets remaining from the 30 tablets he was prescribed at discharge. Police and the coroner speculated that he sold some of the tablets to afford the final high. Police found five used naloxone (Narcan^®) packages in the man’s car—these signaled a history of successful opioid reversals. The toxicology report showed alprazolam, heroin, and the drug that likely killed him: fentanyl. His mother, a nurse, told police that she had little contact with him recently; she knew only that he used drugs and favored heroin. In his car, police and the coroner found completed papers for drug rehabilitation filled out nine days earlier—a missed opportunity that could have prevented his death. ¹

Case Report 2, December 2019

A 22-month-old girl was found unresponsive in her parents’ home in Rolla; she could not be revived. Her mother told police that she and her daughter had fallen asleep on the couch. A criminal investigation found fentanyl on a nearby coffee table, the probable source of the fentanyl identified in the girl’s toxicology results. Before she fell asleep, the girl was eating fish crackers at the table her parents used to cut drugs. The couple faces murder charges. ^1,2

Fentanyl and the Power to Kill

Fentanyl is a potent opioid and 50–100 times as potent as morphine. ^{3, 4} It takes 2 mg (or less) of fentanyl, about the weight of 3 grains of sugar, (Figure 1), to kill an adult who is not opioid-tolerant; less to kill a child, and still less for some highly potent fentanyl analogues. Carfentanil, approximately 100 times as potent as fentanyl, has the potency to tranquilize an elephant with a single carfentanil dart.^5,6 The potency of fentanyl and its analogues, together with low cost, makes fentanyl very attractive to drug dealers to add to a drug such as heroin or even totally replace heroin, which is relatively expensive. Drug dealers are now adding fentanyl to other drugs, including cocaine, methamphetamines, and counterfeit opioid pills.^{7, 8, 9}

Figure 1.

A lethal dose of fentanyl (2 mg) and penny.¹⁰

Illicitly manufactured fentanyl (IMF) is fentanyl manufactured outside of the controlled conditions of pharmaceutical laboratories. IMF can possess several forms, for example in the form of powder or pressed pills, or in gel capsules. It is most commonly found combined with other drugs, especially heroin. It is increasingly found in other illicit substances including cocaine and counterfeit pills. The DEA has reported a large increase, from 5,483 reports (2014) to 15,179 reports (2015), in law enforcement seizures of drugs containing IMF.⁸ Because many experts refer to IMF as fentanyl, we use the terms ‘fentanyl’ or ‘illegal fentanyl’ in this report. We clarify that the synthetic opioids responsible for fatal narcotic overdoses are illicitly manufactured and not diverted from the legal prescription supply.

To understand Missouri’s fentanyl problem and how it relates to national trends, we used national toxicology lab data, interviews with Drug Enforcement Agency (DEA) personnel and online government data, reports gathered from CDC Wonder data, other federal reports, and the book Fentanyl, Inc.: How Rogue Chemists Are Creating the Deadliest Wave of the Opioid Epidemic by Ben Westhoff (Atlantic Monthly Press, 2019). Data for the state of Missouri was obtained from the Missouri Department of Health and Human Services (DHHS) statistics and interviews with Evan Mobley and Andrew Hunter of Missouri DHHS. We begin by looking at the national problem of opioid overdoses.

Fentanyl is Driving the U.S. Overdose Pattern

Drug overdose rates in the U.S. are driven by opioids: 69.5% of drug overdose deaths in 2018 involved an opioid. ¹² Since 2015, most of these deaths involve synthetic opioids, primarily fentanyl (Figure 2). From 2017 to 2018, the U.S. experienced a decline of 2% in deaths from all opioids.¹² There was a decline of 13.5% in deaths from prescription opioids and a decline of 4.1% from deaths due to heroin; however, there was a 10% increase in deaths due to synthetic opioids, primarily fentanyl.¹²

Figure 2.

Drug overdose deaths, 1999–2018. Center for Disease Control and Prevention¹¹

Fatal drug overdose statistics are taken from ICD-10 coding for drug overdose deaths on death certificates. The drug overdose code for fentanyl and related synthetic narcotics is T40.4: “death from synthetic opioids other than methadone.” This category includes not only fentanyl and fentanyl analogues but also other synthetic narcotics such as U-47700, a street drug known as “pink,” “pinky” or “U4” and associated with an increasing number of fatal opioid overdoses.^13–16

These data have limitations, as Nora Volkow, MD, of the National Institute on Drug Abuse (NIDA) stated, “Unfortunately, comprehensive toxicological testing is not performed in many cases, or the results are not recorded on death certificates, so the reported numbers of fatal opioid overdoses and overdoses due to fentanyl might not capture the full scope of the epidemic.”¹⁷ Novel fentanyl analogues often cannot be identified by many toxicology laboratories and consequently are underreported.^{13, 18}

How Illegal Synthetic Opioids Including Fentanyl Arrive in the United States

Figure 3 shows two means of entry of illegal synthetic opioids into the U.S.: a route into the U.S. by the postal service, and routes into the U.S. used by drug traffickers. In both cases, Chinese chemical factories are the source of these synthetic opioids arriving in the U.S.^{19, 20, 21} Clandestine laboratories in Mexico convert Chinese fentanyl precursors to fentanyl and combine IMF with heroin.^{21, 22} The Mexican cartels “tend to use crude methods” to make it and “they just take the fentanyl and stir it with a spoon,” said Doug Coleman of the DEA.²³ Illegal fentanyl is then trafficked into the U.S. market, already combined with heroin and other drugs. The U.S. General Accountability Office has determined that Canada, as well as Mexico, is a supply route for drug traffickers.¹⁹

Figure 3.

Illicit synthetic opioid flows from China. Fentanyl and analogues arrive in the US either directly via mail or trafficked by narcotic distributors. Modified from GAO-18-205.¹⁹

American drug dealers can order fentanyl and analogues to be sent by mail from China, often diverted through another country.²⁴ One Chinese drug dealer who operates openly on the Chinese social media We Chat said that sending drugs through the Chinese mail to the U.S. is easy: “We have our people in the postal companies.” ²⁴ Chinese sources can be found on the Internet that will ship fentanyl analogues that are still legal in China.²⁴ Chinese dealers can also provide fentanyl and analogues that are now illegal in China, using underground sites on the dark web and accepting payment for the drugs with underground currency such as Bitcoin.²⁵ Shipment within the U.S. for all these drugs is illegal, so packages are misleadingly labeled and often shipped via other countries, to avoid seizure by U.S. authorities. Unfortunately, most packages arrive to the U.S. drug dealer or consumer intact.

New Fentanyl Analogues from Chinese Factories

One reason for the proliferation of fentanyl analogues is that many of these variants are still legal in China. Despite ongoing negotiations with the U.S. the Chinese government chooses not to regulate the entire class of fentanyl drugs but instead regulates fentanyl itself and a subset of fentanyl analogues, which it schedules one at a time, if it chooses to schedule them at all.²⁶ A New York Times article describes the Chinese chemical industry as “vast, and poorly supervised, with between 160,000 and 400,000 chemical companies operating legally, illegally, or somewhere in between.” ²⁷ Besides fentanyl and analogues, the industry produces large quantities of inexpensive generic drugs and pharmaceutical ingredients used by more advanced pharmaceutical companies to synthesize more profitable medicines.²⁷

Chinese chemists are adept at developing new analogues not yet regulated in China or other countries, and their companies can sell these legally on the Internet without penalties in China, staying a step ahead of the Chinese government.²⁶ In this way, Chinese chemical factories can follow Chinese regulations and continue to sell fentanyl analogues and precursors on the open Internet. Local authorities favor industrial growth, which is substantial for the thousands of successful Chinese chemical companies.²⁸

There are many ways to modify fentanyl and retain activity; thus dozens of new compounds continue to be created.²¹ Fentanyl is modified by replacement of its propionyl chain or by replacement of its ethylphenyl moiety. The resulting analogues are further modified by substitution with fluoro-, chloro-, or methoxy-groups at the N-phenyl ring, to create analogues such as isobutyryl fentanyl-alpha-methylfentanyl butanamide.^{21, 29} Toxicology reports from overdose victims increasingly demonstrate a number of fentanyl analogues such as acryl fentanyl. ²¹

Wuhan, China is Headquarters for Chinese Fentanyl and Fentanyl Precursor Production

“The bulk of them (fentanyl precursors) seemed to come from a single corporation,”³⁰ run by Ye Chuan Fe, purportedly “once the richest man in Wuhan.”³¹ Ye controls Yuancheng Group, a legal conglomerate that includes many chemical manufacturers that produce a wide array of chemicals from food additives to pharmaceuticals. Yuancheng’s success has been repeatedly praised by Communist Party officials.³² Another chemical company based in Wuhan selling fentanyl and analogs is 5A Pharmatech, led by Yan Xiaobing, who was placed on the Justice Department’s list of international drug traffickers.³³

Chinese chemical and pharmaceutical companies “continue to operate with little oversight,” concluded a 2017 report about fentanyl from the U.S.-China Economic and Security Review Commission.³⁴ Conditions in these labs vary—some labs are clean and up to U.S. pharmaceutical standards. However retired DEA agent Dennis Wichern, said, “Some of the pictures of these Chinese labs are sickening. It reminds me of the old meth-lab days when I worked in Missouri.”³⁴

A newsletter in 2020 from Ben Westhoff stated that disruption in the supply chain of fentanyl from China resulted in a shortage of opioids available from dealers. This, in addition to social distancing measures and fears regarding COVID-19, resulted in increased difficulty in obtaining drugs. Very preliminary data demonstrated a transient decrease in opioid-related deaths in the St. Louis area. Dr. Rachel Winograd, Associate Professor at UMSL’s Missouri Institute of Mental Health and founder of MOHOPE.org and NOMODEATHS.org heard from partners on the ground who noticed an increase in people who use drugs who say, in effect, it is “impossible to find my drug of choice. I’m ready to talk about treatment.”³⁵ Police in Jefferson County and Phelps County confirmed that prices for narcotics on the street rose somewhat.^{36, 37}

Missouri Recently Topped the Nation in Growth Rate for Overdose Deaths

Missouri reflects the national trends, with most drug overdose fatalities related to opioids.¹² Recent trends nationally show an overall decrease in death rates from opioids, including prescription opioids and heroin. Missouri deviated from this trend recently and for a brief time was the state with the largest absolute and percentage per year increase in opioid-related overdose fatality rates. Rates per capita rose in 2018 over the previous year (18.3% and 3.1/100,000).¹² This increase occurred despite an overall national decrease in U.S. opioid-related death rates in the same period.

When the data is disaggregated among counties, a clearer picture emerges. If St. Louis City and County numbers are excluded from Missouri, overdose deaths decreased about 6%—better than the national average. However, in St. Louis City and County, overdose deaths increased by 27%. The majority of these overdoses occurred in black males, with 90% of these deaths associated with fentanyl—compared to 78% of overdose deaths in 2017.^{38, 39} While the disparity is not surprising, the magnitude of the disparity is. The black community is North St. Louis City and County face well-documented longstanding problems in access to care, health resources, and trust of health care messaging. These results can guide future funding in more equitable and effective prevention, harm reduction, and treatment.

The map in Figure 4 shows the crude opioid death rate per capita for each county in Missouri. St. Louis city has the highest opioid death rate in the state, followed by Jefferson and Franklin Counties, which belong to the urban fringe areas that demonstrate the highest opioid mortality rates nationally.^{40, 41} Jackson County, which includes Kansas City, has lower opioid death rates than some rural areas, much lower than found in St. Louis. Brandon Costerison, of the St. Louis chapter of the National Council on Alcoholism and Drug Abuse (NCADA), states St. Louis is one of the top five urban regions in the country for opioid-related deaths. ⁹ In explaining St. Louis’ high overdose rate, DEA’s National Drug Threat Assessment, December 2019, found that Chicago-based street gangs in St. Louis, with ties to the national Crips gang, are the main source of the area’s heroin.⁷ Costerison cites second-hand sources that identify Omaha and Dallas as the main suppliers for Kansas City, with entirely different sources for their heroin.⁹ These five-year rates obscure some recent changes, especially the rise of deaths in rural areas. The number of opioid deaths rose 50% (from 12 to 24) in Boone County from 2017 to 2018.⁴⁰ Stacy Huck, a staff member in the Boone-Callaway County medical examiner’s office, found most overdoses were either fentanyl or methamphetamine (“meth”) related.⁴² Boone County Police Sgt. Brian Leer said, “Meth [sic] used to be the drug we battled here. Meth labs dropped off when Mexican labs began producing methamphetamines. It’s fentanyl in heroin that is driving the overdoses now. Boone County has a problem with ‘Gray Death’ [the street name for the gray-colored mix of heroin and varying amounts of fentanyl, fentanyl analogues and U-47700]. The route is Chicago to St. Louis and then across Missouri. The stigma of heroin has gone away—it’s more accepted in the user world.”⁴³ Bill Callahan, head of St. Louis Division DEA, said, “Meth is still a big problem in western Missouri. We have some instances of meth with fentanyl contamination.”⁴⁴ In fact, the street slang term ‘goofball’ now refers to a combination of methamphetamine and either heroin or fentanyl.⁴⁵

Figure 4.

Lethal opioid overdoses in Missouri, 2014–2018, statistics from MO DHHS ⁴⁰

Accounting for Opioid Deaths: Missouri is a “Street drug” State, and Not a “Prescription Overdose” State

In 2018, Missouri providers wrote 63.4 opioid (fentanyl included) prescriptions per 100 persons, somewhat more than the national average rate of 51.4 per 100.⁴⁶ There are a few outlier Missouri counties, including Dunklin, Butler, St. Francois, and Howell, with opioid prescription rates from 2017 data over two-and-a-half times the national average. Dunklin County ranks the highest with 148.6 opioid prescriptions per 100 people.⁴⁷ Only St. Francois County of the four counties listed above ranks within the top quarter of opioid overdose counties in the state, and Dunklin County has one of the lowest opioid overdose fatality rates in the state: 0.66 persons per 100,000 (one person died 2014–2018).³⁹ St. Louis City, with the highest rate of opioid deaths, ranks below the national average for opioid prescriptions: 42.5 per 100 persons.⁴⁷ Evan Mobley of the Missouri DHHS advised caution about citing numbers of prescriptions written as the sole measure of controlled substance prescribing habits, without considering the duration of the prescription.⁴⁸ Careful prescribing practices remain the best approach for providers.

Fentanyl and Fentanyl Analogues in America: Fentanyl is Moving West

Toxicology laboratory reports gathered by the CDC demonstrate an increasing national rate of fentanyl overdoses (Figure 5). Toxicology laboratory reports show fentanyl death rates are highest in the eastern part of the country. Missouri is one of only nine states with a high rate (29 or more per 100,000 persons aged 15 or older in 2017) of fentanyl toxicology reports.⁴⁹ All these states except Missouri are east of the Mississippi River (Figure 5a). However the highest growth rates in fentanyl reports are from toxicology labs further west. Missouri was one of eight states that had a growth rate in reports of 150% or more. All these states except three are west of the Mississippi River (Figure 5b). Fentanyl analogue reports demonstrate a similar westward movement.

Figure 5a.

Fentanyl toxicology reports, per capita.

Figure 5b.

Fentanyl toxicology reports, rate of change. ⁴⁹

Missouri was one of 14 states to have more than 200 reports of the non-fentanyl synthetic opioid U-47700 in 2017, and had the fourth highest rate of growth in U-47700 (pink) reports: 854% increase from 2016 to 2017, behind only South Carolina, Illinois, and Michigan.⁴⁹

One reason for the east-to-west gradient in fentanyl-related overdose rates is the regional monopolies that control access to heroin, which offer only the type of heroin their distributor can supply.⁵⁰ Powder heroin, available in Eastern states, is relatively easy to combine with fentanyl.^51,52 “Black tar” heroin, a dark, sticky opium-like substance predominant in western states, is difficult to mix with fentanyl. Keven Wandler, MD, Chief Medical Officer at Advanced Recovery Systems, stated, “I have not yet heard stories of people lacing black tar heroin with fentanyl.⁵³ But the market is changing: toxicology lab reports demonstrate that fentanyl is increasingly found in more western states. This march westward is now playing out in Missouri.

Conclusion

Missouri’s At-Risk Demographic

One of the major driving forces for the use of fentanyl, both knowingly and unknowingly, is the heroin market in the U.S. In several ways, the opioid crisis is founded on economic distress within communities across Missouri. Without any adulteration, the average retail price of pure heroin has significantly increased. Synthetic opioids, both fentanyl and analogues, are available at a far cheaper price than street heroin as they are cheaper to manufacture.⁶ By adding cheap synthetic opioids, the price per milligram of the final product has almost halved from 2010 to 2014.^{6, 51} The decrease in prices for fentanyl-adulterated heroin and the increased opioid potency, which can vary significantly among opioid batches, equate to more users, more demand and more danger for each user. In recent years, the heroin market has expanded from the inner-city domain to towns and rural locations, which puts most of Missouri at risk.^{6, 51}

The social conditions that correlate with the increased use of illegal drugs: poverty–both rural and urban, unemployment, and homelessness are expected to persist and may get worse in the current pandemic. Economic constraints may reduce access to addiction treatment, which is of primary importance in reducing opioid deaths.

One new and unknown factor in Missouri is the new medical marijuana law 19 CSR 30–95 passed in 2018. Bill Callahan, head of DEA’s St. Louis District, said, “Marijuana is not necessarily a gateway drug, but it is a gateway to a culture shift because you’re running with a different group of people.” ⁴⁴ Speaking of teenagers’ ability to make decisions, Callahan said, “The brain is not fully developed.”⁴⁴ Thus as Callahan sees it, there may be more exposure to different drugs once a young person becomes acquainted with a new group of people who will expose them to new and dangerous drugs, including fentanyl and analogues.

Epilogue

Preliminary Data Show Opioid Deaths Continue to Rise in Missouri

In early 2020, when the Chinese government shut down activity in and around Wuhan due to the COVID-19 virus, the illicit opioid supply chain was disrupted. Yet the communists acted quickly to promote economic recovery. A South Central Drug Task Force officer found that “heroin/fentanyl continue to be available in the area for roughly the same prices.” The officer noted unusually high numbers of Narcan use in some rural Missouri counties.⁵⁴

We queried two county medical examiner offices who noted a year-on-year increase in opioid-related deaths. The St. Louis County Medical Examiner’s Office reports preliminary opioid-related deaths for the first five months in 2020 were up 17% from the year before (112 deaths in 2019 and 131 in 2020). Because of short-staffing (and an increase in overdose cases), it is difficult keep current with data entry and these preliminary 2020 totals are expected to rise.⁵⁵

Outstate areas are also on track to equal or exceed overdoses totals of previous years. The Boone County Medical Examiner’s office which performs examinations for Boone and Callaway counties has preliminary data showing opioid deaths are increasing. Boone and Callaway counties have already had respectively nine and three cases of known opioid deaths for the first half of 2020, with a further 34 and 11 cases pending final assignment of cause of death.⁵⁶ Boone and Callaway are on track to outpace the 2014–2018 annual averages of 13 and 4 fatalities, respectively.

Brandon Costerison of NCADA has summarized the situation for the illicit drug user in Missouri: “The drug supply is in chaos. Due to social distancing, those users may be using alone at home, and people don’t know to check on them.” ⁵⁷ In the era of COVID, narcotic addicts who overdose are dying alone at home.