White opioids: Pharmaceutical race and the war on drugs that wasn’t

White opioids: Pharmaceutical race and the war on drugs that wasn’t


The US ‘War on Drugs’ has had a profound role in reinforcing racial hierarchies. Although Black Americans are no more likely than Whites to use illicit drugs, they are 6–10 times more likely to be incarcerated for drug offenses. Meanwhile, a very different system for responding to the drug use of Whites has emerged. This article uses the recent history of White opioids – the synthetic opiates such as OxyContin® that gained notoriety starting in the 1990s in connection with epidemic prescription medication abuse among White, suburban and rural Americans and Suboxone® that came on the market as an addiction treatment in the 2000s – to show how American drug policy is racialized, using the lesser known lens of decriminalized White drugs. Examining four ‘technologies of whiteness’ (neuroscience, pharmaceutical technology, legislative innovation and marketing), we trace a separate system for categorizing and disciplining drug use among Whites. This less examined ‘White drug war’ has carved out a less punitive, clinical realm for Whites where their drug use is decriminalized, treated primarily as a biomedical disease, and where their whiteness is preserved, leaving intact more punitive systems that govern the drug use of people of color.

Keywords: addiction, whiteness, prescription opioids, heroin


The US ‘War on Drugs’ has had a profound role in reinforcing racial hierarchies. Drug offenses accounted for two-thirds of the rise in the federal inmate population and more than half of the rise in state prisoners between 1985 and 2000, with more than half of young Black men in large cities in the United States currently under the control of the criminal justice system (Alexander, 2010), and middle aged Black men more likely to have been in prison than in college or the military (Rich et al, 2011). Although Black Americans are no more likely than Whites to use illicit drugs, they are 6–10 times more likely to be incarcerated for drug offenses (Bigg, 2007Goode, 2013). Alexander (2010)Wacquant (2009)Hart (2013) and others make the case that the criminal justice system is, in effect, a new state-sponsored racial caste system.

Meanwhile, a very different system for responding to the drug use of Whites has emerged. Beginning in the 1990s, rates of prescription opioid misuse – primarily OxyContin® – began to rise dramatically, particularly among Whites. The press reported a suburban and rural White prescription opioid epidemic (Tough, 2001Ung, 2001ab) as prescription drug overdose deaths rose 117 per cent between 1999 and 2012 (CDC, 2014). By 2010, the National Institute on Drug Abuse (NIDA) noted increasing numbers of prescription opioid dependent people turning to heroin as prescription opioids became harder to misuse (Volkow, 2014) because of new prescription monitoring programs and tamper resistant opioid formulations. Thousands of White addicted people found themselves the center of media and political debates about how the country should respond to the latest drug crisis.

The public response to White opioids looked markedly different from the response to illicit drug use in inner city Black and Brown neighborhoods, with policy differentials analogous to the gap between legal penalties for crack as opposed to powder cocaine. This less examined ‘White drug war’ has carved out a less punitive, clinical realm for Whites where their drug use is decriminalized, treated primarily as a biomedical disease, and where White social privilege is preserved. This ‘White drug war’ has historical precedents in which predominantly White populations have used social privilege to invoke ‘medical need’ to secure or maintain access to powerful sedatives or stimulants in the mid to late twentieth century (see Herzberg, 2013). But in the case opioids, addiction treatment itself is being selectively pharmaceuticalized in ways that preserve a protected space for White opioid users, while leaving intact a punitive, carceral system as the appropriate response for Black and Brown drug use.

Whiteness is a sociocultural achievement: it is actively maintained through the shoring up of social boundaries distinguishing White and from not White (Frankenberg, 1993Allen, 1994Fine et al, 1996Daniels, 1997Wray, 2006Roediger, 2007Twine and Gallagher, 2008Hughey, 2010). The seeming inevitability and naturalness of whiteness allows those within the category ‘White’ to be unmarked, to think of themselves as simply human and without race, while those who fall outside the bounds of whiteness are the racialized Other (Dyer, 1988). Scholars have explored the ways in which whiteness shapes housing (Low, 2009), education (Leonardo, 2009), politics (Feagin, 2012), law (Lopez, 2006), research methods (Zuberi and Bonilla-Silva, 2008) and our understanding of society (Lipsitz, 2006 [1998]Feagin, 2010). Yet, despite almost two decades of research in the field of whiteness studies, there remains relatively little literature that explores the myriad connections between whiteness and health in the US context (Katz Rothman, 2001Daniels and Schulz, 2006Jones, et al, 2008Daniels, 2012Daniels, 2013) and only a few studies exploring the issue of whiteness and psychoactive substances (Steiner and Argothy, 2001Murakawa, 2011Daniels, 2012Linnemann and Wall, 2013).

In one of the only studies to explicitly look at how drug policy is used to carve out White spaces exempt from punitive more approaches, Lassiter (2015) takes a historical look at the roots of the White opioid crisis of today. Looking back to marijuana policies of the 1970s, he states: “exemptions created for white middle-class participants in the underground market-place were not merely epiphenomenal but rather constitutive of the expansion of the carceral state (p. 127)”. The drug war operates because of a reciprocal relationship between the criminalization of blackness and the decriminalization of whiteness. Lassiter notes that, when the Rockefeller Drug Laws instituted harsh mandatory minimums, White suburban youth found themselves facing significant jail time for low-level marijuana possession. Parents of White suburban youth banded together to create policy changes that exempted marijuana from the Rockefeller Drug Laws, essentially decriminalizing low-level possession in some jurisdictions. This was possible, in part, because of the racial dynamics and the portrayal of White youth as sympathetic victims of the organized narcotics trade. The relative paucity of studies, such as Lassiter’s examining the constitutive role of whiteness in the drug war, is remarkable given the wealth of sociocultural research on pharmaceuticals, addiction and race, which has illuminated myriad ways that the biochemical stratification of people of African and Latin American origin has been represented and materially shaped in sites ranging from genetics labs, medical clinics and neighborhoods, to popular media, courtrooms and policy debates (c.f. Campbell, 2000Courtwright, 2001Fullwiley, 2007Singer, 2008Bourgois and Schonberg, 2009Roberts, 2011Tiger, 2012).

While not focused on addiction, some scholars have traced the ways that medicine has always been racialized and used to justify less punitive responses for Whites than Blacks. For example, Solinger (2013)traces how a racial divide was produced and maintained by the discourses surrounding “illegitimate” childbirth and the medicalization of abortion. While abortion became available and somewhat acceptable for Whites, the welfare system was being used to publicly shame and punish women of color who had children out of wedlock. Other studies trace how race became embedded in medical technologies and rhetoric in ways that become taken for granted and that reinforce notions of racial difference. Pollock (2012), in a study of the racialization of heart disease, notes that whiteness is reinforced by its using the famous Framingham study as the norm. Braun (2014) traces the ways that the spirometer, originally developed in the antebellum South to demonstrate the physiological inferiority of Black slaves, continues to naturalize racial difference in contemporary usage through “race correction” of “normal” reference ranges. These works remind us that racial projects are inherently implicated in medicine and that race is reified in discourses of legitimacy, normativity and technological precision.

White race is encoded into biomedical technologies and practice in particularly covert, implicit rather than explicit ways and in ways that may not be intentional on the part of key actors. Our argument here focuses on racializing consequences of pharmaceutical reason that stem from pre-existing structures of exclusion, inclusion, political pragmatism and industry that over-determine the strategies of scientists, treatment advocates, policymakers and pharmaceutical executives. Opioids in the United States are subjected to a racial biopolitics that constrains available strategies, even to those who oppose social hierarchies and strive to de-racialize drug policy. Efforts to de-racialize any arena of life in the United States, which do not directly address racism, risk reproducing racial hierarchy, because White privilege is typically reproduced by eliminating racial references from seemingly universal policies and practice; in the latter part of the twentieth century the social policy reforms that did the most to intensified racial inequalities in income, employment and incarceration were undertaken under the guise of “color blind ideology” (Alexander, 2010).

This article uses the recent history of White opioids – the synthetic opiates OxyContin® and Suboxone®that gained notoriety starting in the 1990s in connection with epidemic prescription medication abuse among White, suburban and rural Americans – to show how American drug policy is racialized, using the lesser known lens of decriminalized White drugs. Examining four ‘technologies of whiteness’ (neuroscience, pharmaceutical technology, legislative innovation and marketing), we trace a separate system that categorizes and disciplines drug use among Whites, while not naming White race explicitly, given that White is the unmarked, assumed norm. Maintaining the boundaries of whiteness under racially segregated drug policy requires constant vigilance and ongoing political work. Our thesis is that these technologies of whiteness are fueled by two biopolitical currents that trade on hidden or misrecognized racial coding: on one hand, a partnership of the pharmaceutical industry with lawmakers who are conscious of the racial symbolism of addiction risk and legitimate use of opioids, and on the other, an unconscious collusion of liberal neuroscientists seeking to decriminalize opioid misuse and democratize treatment using a discourse of addiction as a brain disease, while failing to recognize the (White) racial coding in the universal brain disease framework and its disparate consequences.

Addiction Neuroscience as a Technology of Whiteness

The mass incarceration of people of color for drug offenses is, in part, legitimated by the belief that drug use results from a failure of will or morality. People are responsible for their use and, therefore, must be held accountable or punished. However, at the same time that more punitive War on Drug policies were enforced in Black and Latino city neighborhoods, President Bush I ushered in the Decade of the Brain at the National Institute on Drug Abuse. The richly funded neuroscience program at NIDA in the 1990’s provided a scientific rationale for addiction as a clinical disease, focusing on altered brain chemistry as the source of addiction and on neuroactive pharmaceuticals and clinical (rather than law enforcement) interventions as the appropriate response. Simply put, neuroscience provided a scientific rationale for treating addictions – at least some addictions – as disease needing medical intervention rather than as crime requiring punishment. While the race of the addict was excluded from this universalizing biological discourse, the very absence of a language of race indexed White subjects. The scientists involved in this project probably did not intend to exacerbate racial inequalities with their work; on the contrary, many saw their efforts to establish the neurochemical basis for addiction as a way to counteract the social injustice of addiction stigma, and, by extension, racial injustice. Yet, the implicit racial logic of universalist clinical research, which has long held the 70 kg White male as its standard subject (Epstein, 2007), channeled the efforts of even egalitarian neuroscientists toward stratified results.

In the United States, NIDA spent millions of dollars promoting one simple message: ‘addiction is a brain disease’. In 1997, Alan Leshner, then Director of NIDA, published a landmark article entitled, “Addiction is a Brain Disease, and It Matters”. In the article, Leshner argues that addiction is as much a medical as a social problem and that the field and the public has focused too much attention on the latter:

That addiction is tied to changes in brain structure and function is what makes it, fundamentally, a brain disease. … Understanding that addiction is, at its core, a consequence of fundamental changes in brain function means that a major goal of treatment must be to either reverse or compensate for those brain changes.

(1997, p. 46)

It is this perspective that has guided NIDA since. It has also permeated the field of addictions research through the 1990s, as demonstrated by a landmark article in the Journal of the American Medical Association, co-authored by four prominent addictions researchers, and entitled “Drug Dependence, A Chronic Medical Illness”. The article argued that drug dependence was comparable to asthma, diabetes and hypertension in terms of heritability, causation, pathophysiology and adherence to treatment, and that it should be treated as a chronic medical illness for purposes of treatment approaches, insurance coverage and outcome measures (McLellan et al, 2000). In 2003, Nora Volkow, a prominent neuroscientist who pioneered the use of PET scans in addiction research, became the Director of NIDA. Since her appointment, she has vociferously championed the brain disease model in both NIDAs scientific and public education arms. For example, in 2005 NIDA underwrote a widely-cited issue of Nature devoted to addiction neurobiology. NIDA has also produced a series of curricula for elementary and high school students to explain addiction. These include: “Brain Power”, “Mind Over Matters”, “Heads Up” and “The Brain”. NIDAs educational materials closely track the scientific literature. NIDAs power in the field of addiction neuroscience has led one scholar to describe them as largely responsible for making “the neuroscientists’ laboratory … an obligatory passage point for the production of truths about addiction” (Vrecko, 2010, p. 58).

Addiction neuroscience is connected to whiteness and addiction is three key ways. First, whiteness and health are implicated in the use of brain imagery. Images, such as PET scans, of the ‘addicted brain’ are increasingly popular in addiction studies and in reporting on addiction. While images of drug-related brain damage or craving-induced brain activity are compelling and are liberally used in NIDAs educational materials, several scholars have noted that imaging technologies, far from being objective or neutral, are shaped by their social and economic context and involve a series of subjective decisions by researchers (see especially, Beaulieu, 2001Dumit, 2004Joyce, 2005). What is striking about brain images of addiction is that they are unmarked by race: they convey a sense of universality and timelessness that, by omitting racial identity, help to expunge racial identity of the addict leaving a White, because racially unmarked, backdrop. Brain scans here operate as the unmarked White norm similar to the way in which the Framingham study of predominantly White participants became the norm for heart disease (Pollock, 2012). A neuroscientific model of addiction as brain disease, which extracts the brain from the racially marked addicted body, thereby helps to unmark (biological) addiction, defining it as a human universal, and therefore White. The neuroscientific reframing of addiction is, therefore, a technique for the racial recoding of (certain types of) addiction and of (some) addicted people, which extracts addiction from the association with Black and Latino people inherent in a social, moral, or criminal framing of addiction.

Neuroscience and whiteness are further connected through the silence in neuroscientific literature about the role of environmental factors contributing to addiction. Social determinants of health, such as geography, income, education and housing are largely omitted from the description of research subjects and from the lists of relevant variables in neuroscientific papers. Environmental factors in addiction neuroscience are generally reduced to cues or triggers (for example, studies demonstrating how brain ‘lights up’ when a drug user is shown a picture of heroin or cocaine). Even when environmental forces are acknowledged, they are of interest primarily for the biochemical processes they engender. Volkow and Li explain the “neural consequences of environmental risk”:

Low socioeconomic class and poor parental support are two other factors [along with drug availability] that are consistently associated with a propensity to self-administer drugs, and stress might be a common feature of these environmental factors […T]here is evidence that corticotropin-releasing factor (CRF) might play a linking role through its effects on the mesocorticolimbic dopamine system and the hypothalamic pituitary-adrenal axis. […] If we understand the neurobiological consequences underlying the adverse environmental factors that increase the risk for drug use and addiction, we will be able to develop interventions to counteract these changes.

(2005, p. 1436)

Here, environmental influences are acknowledged but understood only in the context of how the stress they induce affects the dopamine system. Volkow and Li (2005) go on to suggest that the future addiction interventions may include medications that act synergistically with behavioral therapies to mitigate the impact of stress. Absent from their view of addiction are features of neighborhood environment or social roles that might hint at the context of drug use, and therefore the race of drug users and their stressors. They offer an individually focused clinical and physiological, rather than a public health, model of addiction.

The third connection between addiction neuroscience and whiteness is what neuroscience frames as the appropriate response to addiction. When addiction is conceptualized as a ‘brain disease’ involving genetically and physiologically determined neuroreceptors, what is called for is a medication that specifically targets faulty neuroreceptors. This stands in stark contrast to the prevalent response to addiction in the United States as part of the War on Drugs in which incarceration is the ready response. When addiction is framed as a brain disorder, rather than a crime, its cultural work to racially recode prescription opioid addiction as White is unrecognized. This ultimately leads to a bifurcated discourse of White addicts as having a ‘brain disease’ and needing ‘treatment’, and of non-White addicts as ‘criminals’ that require incarceration to protect the public.

It seems, however, that some neuroscientists are unaware of the role their work is playing in reinscribing racialized notions about drug users. Indeed, some addiction neuroscience researchers have said that their political project was to delink addiction from crime. They see themselves as reframing addiction as a brain disease for the precise purpose of destigmatizing and decriminalizing drug use and bringing it under the purview of medicine, rather than the criminal justice system. Dackis and O’Brien, for instance, claim that neuroimaging will:

substantiate the biological basis of addiction and […] ultimately erode entrenched societal attitudes that prevent addiction from being evaluated, treated, and insured as a medical disorder.

(2005, p. 1431)

Such researchers believe that promoting a neurological basis for addiction will erode the persistent idea that addiction is “a character flaw rather than a bona fide brain disease” (Chou and Narasimhan, 2005, p. 1427), leading to the end of stigma and criminalization. Importantly, both models – the moral/criminal and the medical – root the etiology of addiction at the level of the individual, absenting from consideration structural and environmental factors.

These discussions do not explicitly reference race, but it is notable that the neurobiological, universal, by extension ‘White’ and therefore less stigmatizing and criminalizing concept of addiction, was aggressively developed during a decade (the 1990s) when middle class, White heroin use was growing. This change in the demographics of heroin consumption was because of an influx of heroin from newly planted poppy fields in Colombia, whose cartels were competing with established Middle Eastern and Asian heroin distributors by dramatically lowering the price and increasing the purity of the heroin they sold in the United States cities. This attracted middle class users who found they could snort instead of injecting the purer heroin (Hamid et al, 1997). In addition, with the 1996 approval of OxyContin® as a “minimally addictive pain reliever” marketed to generalist physicians in rural and suburban areas for their use in moderate pain (Van Zee, 2009), by the late 1990s the specter of the coming White prescription opioid addiction epidemic had been raised.

By focusing on brain neurochemistry, the neuroscientific model of addiction, referred to by many neurophysiology researchers as ‘chronic relapsing brain disease’, erases and obscures the role of race and other social differences in ways that privilege whiteness. The brain disease model of addiction reduces any discussion about poverty, exposure to drugs, racism and other environmental factors to problems of the brain and its response to ‘stress’. Social issues, such as the mass incarceration of African Americans under harsh drug laws or the lack of viable economic opportunities beyond the drug trade in Black and Latino neighborhoods, have no place in neuroscientific discourse. As Nancy Campbell notes, “as an ideological code, CRBD [chronic relapsing brain disease] does not focus attention on social differences, including the differential histories and cultural geographies within which their subjects encounter drugs” (2010, p. 101).

As we discuss further below, this neuroscientific racial recoding of prescription opioid addiction was one basis for legislative innovations that created a new, separate track for treating the addiction of White opioid users.

Pharmaceutical Technologies of Whiteness

Opioids have long blurred the line between legitimate medications and drugs of abuse. Morphine went into widespread use during the Civil War in the treatment of injured soldiers, and among middle class White Victorian housewives for a range of problems including menstrual pain. Morphine ‘habits’ only began to be seen as problematic at the end of the nineteenth century; in 1898 Bayer Corporation introduced heroin as a non-addictive cure for morphine addiction as well as a cough syrup for children. However, changes in medical practice and international drug policy led the media and policymakers to associate opiates with poverty and ethnic minorities, and prohibitionists succeeded in banning opiate maintenance from clinical practice with passage of the 1914 Harrison Act (Musto, 1999Courtwright, 2001). Methadone was introduced as a synthetic opioid pain reliever in Germany during World War II when morphine supplies from Asia ran short, was re-introduced in the 1960s as a maintenance medication for heroin addiction following successful clinical trials among African Americans in Harlem (Dole and Nyswander, 1966), and was named a primary weapon in President Nixon’s War on Drugs in 1971 (White, 1998). Methadone quickly become the focus of tight surveillance and regulation by the DEA, however, based on reports of methadone abuse and diversion, and on methadone’s symbolic association with Black and Brown inner city drug use (Hansen and Roberts, 2012). New opioids have therefore undergone a predictable cycle of optimism touted as the holy grail of a non-addictive pain reliever, followed by challenges to their legitimacy as medications, their association with poverty and ethnic minorities, and stigmatization as addictive drugs.

Oxycodone – an addicting opioid as pain med

Oxycodone is a semisynthetic opioid synthesized from thebaine, an opioid alkaloid found in the Persian poppy, and one of the many alkaloids found in the opium poppy. It is a moderately potent opioid pain medication (orally roughly 1.5 times more potent than morphine),[8] generally indicated for relief of moderate to severe pain.[9] Oxycodone was developed in 1917 in Germany[10][11] as one of several semi-synthetic opioids in an attempt to improve on the existing opioids.[1]

Oxycodone is available as single-ingredient medication in immediate release and controlled release. In the United Kingdom, it is available in 10 mg/mL and 50 mg/mL formulation for intramuscular or intravenous administration.[12]Combination products are also available as immediate-release formulations, with non-narcotic analgesic ingredients such as paracetamol (acetaminophen) and nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen.

As it has euphoric effects similar to other opioids, oxycodone is one of the drugs abused in the current opioid epidemic in the United States.[13][14] An abuse-deterrent combination with naloxone is available in managed-release tablets. If injected, the naloxone precipitates opioid withdrawal symptoms and blocks the effect of the medication. However, there have been concerns raised about the effectiveness of the abuse prevention measures.[14][15]

Medical uses

Oxycodone has been in clinical use since 1916,[1] and it is used for managing moderate to moderately severe acute or chronic pain.[16] It has been found to improve quality of life for those with many types of pain.[17] Experts are divided regarding use for non-cancer-related chronic pain, as most opioids have great potential for dependence and have also been alleged to create paradoxical pain sensitivity.

Oxycodone is available as controlled-release tablet, intended to be taken every 12 hours.[18] A 2006 review found that controlled-release oxycodone is comparable to instant-release oxycodone, morphine, and hydromorphone in management of moderate to severe cancer pain, with fewer side effects than morphine. The author concluded that the controlled release form is a valid alternative to morphine and a first-line treatment for cancer pain.[19] In 2014, the European Association for Palliative Care recommended oral oxycodone as a second-line alternative to oral morphine for cancer pain.[20]

In the U.S., extended-release oxycodone is approved for use in children as young as 11 years old. The approved indication is for relief of cancer pain, trauma pain, or pain due to major surgery, in children already treated with opioids, who can tolerate at least 20 mg per day of oxycodone; this provides an alternative to Duragesic (fentanyl) the only other extended-release opioid analgesic approved for children.[21]


In the United States, oxycodone is only approved for oral use, available as tablets and oral solutions. In Spain, the Netherlands and the United Kingdom, oxycodone is also approved for intravenous (IV) and intramuscular (IM) use. When first introduced in Germany during World War I, both IV and IM administrations of oxycodone were commonly used for postoperative pain management of Central Powers soldiers.[1]

Side effects

Main side effects of oxycodone[22]

Serious side effects of oxycodone include reduced sensitivity to pain (beyond the pain the drug is taken to reduce), euphoriaanxiolysis, feelings of relaxation, and respiratory depression.[23] Common side effects of oxycodone include constipation (23%), nausea (23%), vomiting (12%), somnolence (23%), dizziness (13%), itching (13%), dry mouth (6%), and sweating (5%).[23][24] Less common side effects (experienced by less than 5% of patients) include loss of appetitenervousnessabdominal paindiarrheaurine retentiondyspnea, and hiccups.[25]

In high doses, overdoses, or in some persons not tolerant to opioids, oxycodone can cause shallow breathingslowed heart rate, cold/clammy skin, pauses in breathinglow blood pressureconstricted pupilscirculatory collapserespiratory arrest, and death.[25]

Oxycodone overdose has also been described to cause spinal cord infarction in high doses and ischemic damage to the brain, due to prolonged hypoxia from suppressed breathing.[26]

Oxycodone in combination with naloxone in managed-release tablets, has been formulated to both deter abuse and reduce “opioid-induced constipation”.[27]

Dependence, addiction, and withdrawal

The risk of experiencing severe withdrawal symptoms is high if a patient has become physically dependent and discontinues oxycodone abruptly. Medically, when the drug has been taken regularly over an extended period, it is withdrawn gradually rather than abruptly. People who regularly use oxycodone recreationally or at higher than prescribed doses are at even higher risk of severe withdrawal symptoms. The symptoms of oxycodone withdrawal, as with other opioids, may include “anxietypanic attacknauseainsomniamuscle painmuscle weaknessfevers, and other flu-like symptoms“.[28]

Withdrawal symptoms have also been reported in newborns whose mothers had been either injecting or orally taking oxycodone during pregnancy.[29]

Hormone imbalance

As with other opioids, chronic use of oxycodone (particularly with higher doses) often causes concurrent hypogonadism or hormone imbalance.[30]


Oxycodone is metabolized by the enzymes CYP3A4 and CYP2D6, and its clearance therefore can be altered by inhibitors and inducers of these enzymes.[31] (For lists of CYP3A4 and CYP2D6 inhibitors and inducers, see here and here, respectively.) Natural genetic variation in these enzymes can also influence the clearance of oxycodone, which may be related to the wide inter-individual variability in its half-life and potency.[31]

Ritonavir or lopinavir/ritonavir greatly increase plasma concentrations of oxycodone in healthy human volunteers due to inhibition of CYP3A4 and CYP2D6.[32]Rifampicin greatly reduces plasma concentrations of oxycodone due to strong induction of CYP3A4.[33] There is also a case report of fosphenytoin, a CYP3A4 inducer, dramatically reducing the analgesic effects of oxycodone in a chronic pain patient.[34] Dosage or medication adjustments may be necessary in each case.

New Painkillers Reduce Overdose Risk

New Painkillers Reduce Overdose Risk

Summary: Researchers have developed a new pain killer that is on par with conventional opioids, but does not affect respiration, which is the main cause of opioid overdose.

Source: Scripps Research Institute.

Scientists on the Florida campus of The Scripps Research Institute (TSRI) have developed new opioid pain relievers that reduce pain on par with morphine but do not slow or stop breathing — the cause of opiate overdose.

The research, published today in the journal Cell, describes a method for making safer opioid painkillers. According to the U.S. Centers for Disease Control and Prevention, 91 Americans die every day from opioid overdoses — deaths caused when opiates like oxycontin, heroin and fentanyl slow and eventually stop a person’s breathing.

Study leader TSRI Professor Laura M. Bohn, Ph.D., said the research shows that a range of compounds can deliver pain-blocking potency without affecting respiration.

The study builds on two decades of research by Bohn and her colleagues, who long questioned whether the painkilling pathway, called the G protein pathway, could be unlinked from the breathing suppression pathway, called the beta-arrestin pathway.

“One of the questions we had was how good we can get at separating out the pathways, and how much separation do we need to see analgesia without respiratory suppression,” Bohn said.

For the study, the Bohn worked closely with TSRI chemist Thomas Bannister, PhD, to develope new potential drug molecules; they then tweaked their chemical structures to systematically vary the “bias” between the two pathways–G protein signaling and beta-arrestin recruitment. The group developed more than 500 compounds in the past six years, and they found more than 60 that showed bias between signaling assays. They then selected six compounds to represent a wide range in the degree of bias (from those that preferred barrestin2 recruitment to those that almost exclusively preferred G protein signaling) and determined their overall potency for inducing analgesia and respiratory suppression in mouse models.

The researchers found that the new compounds could indeed enter the brain–and all of the compounds were as potent, if not more so, than morphine. The compounds that were less able to promote barrestin2 associations in cells were also less likely to induce respiratory suppression in mice.

pills are shown

In contrast, the painkiller fentanyl was shown to prefer receptor-barrestin2 associations and also had a more narrow safety margin. In short, the fentanyl dose needed to alleviate the perception of pain was closer to the dose that suppressed breathing, which may be why fentanyl is more likely to trigger respiratory suppression at low doses. Fentanyl is a powerful pain killer, but one with a narrow therapeutic window and a history of overdoses. While this issue requires more research, “this at least brings into question whether this may be part of the reason,” Bohn said.

Bohn explained that separating the receptor’s ability to engage in the two pathways can provide a way to separate desired drug effects from side effects.

“I think what we have done here is shown that bias isn’t all or none–that there is a spectrum.” That suggests an opportunity to expand the “therapeutic window,” or the range of doses at which a drug may be administered safely, she said.


Funding: The results announced today are the culmination of nearly six years of work by TSRI scientists including Cullen Schmid, Ph.D., Nicole Kennedy, Ph.D., and Michael Cameron, Ph.D.; as well as former members of the research lab: Jenny Morgenweck, Ph.D., Zhizhou Yue, Ph.D., Kim Lovell, Ph.D. and Nicolette Ross, Ph.D., The work was funded by the National Institute on Drug Abuse of the National Institutes of Health (grants R01 DA033073 and R01 DA038694).

Source: Stacey Singer DeLoye – Scripps Research Institute
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics” by Cullen L. Schmid, Nicole M. Kennedy, Nicolette C. Ross, Kimberly M. Lovell, Zhizhou Yue, Jenny Morgenweck, Michael D. Cameron, Thomas D. Bannister,and Laura M. Bohn in Cell. Published online November 16 2017 doi:10.1016/j.cell.2017.10.035

Scripps Research Institute “New Painkillers Reduce Overdose Risk.” NeuroscienceNews. NeuroscienceNews, 16 November 2017.


Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics

•Mu opioid agonists were made to promote signaling through G proteins or βarrestin2
•Potency was determined for pain relief and respiratory depression in mice
•Fentanyl’s narrow safety window correlates with its preference for βarrestin2
•Increasing signaling through G proteins directly improves the therapeutic index

Biased agonism has been proposed as a means to separate desirable and adverse drug responses downstream of G protein-coupled receptor (GPCR) targets. Herein, we describe structural features of a series of mu-opioid-receptor (MOR)-selective agonists that preferentially activate receptors to couple to G proteins or to recruit βarrestin proteins. By comparing relative bias for MOR-mediated signaling in each pathway, we demonstrate a strong correlation between the respiratory suppression/antinociception therapeutic window in a series of compounds spanning a wide range of signaling bias. We find that βarrestin-biased compounds, such as fentanyl, are more likely to induce respiratory suppression at weak analgesic doses, while G protein signaling bias broadens the therapeutic window, allowing for antinociception in the absence of respiratory suppression.

“Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics” by Cullen L. Schmid, Nicole M. Kennedy, Nicolette C. Ross, Kimberly M. Lovell, Zhizhou Yue, Jenny Morgenweck, Michael D. Cameron, Thomas D. Bannister,and Laura M. Bohn in Cell. Published online November 16 2017 doi:10.1016/j.cell.2017.10.035

Opioid-related hospitalizations in Georgia, Louisiana and West Virginia

AHRQ Stats: Cost Trends for Hospital Stays

From 2005 to 2014, the average inflation-adjusted cost of a hospital stay increased approximately 13 percent, from $9,500 to $10,900. Average costs for stays covered by Medicaid and private insurance increased 16 to 18 percent. Costs rose 8 percent for Medicare stays and 7 percent for uninsured stays. (AHRQ, Healthcare Cost and Utilization Project Statistical Brief #225: Trends in Hospital Inpatient Stays in the United States, 2005-2014.)

Today’s Headlines:

New Interactive Map Highlights State-Specific Trends in Opioid-Related Hospital Stays

A new interactive map from AHRQ allows users to explore state-specific information about opioid-related hospital stays. Users may find, for example:

  • Opioid-related hospitalizations have increased most dramatically in Georgia, where rates nearly doubled between 2009 and 2014
  • West Virginia reported the highest hospitalization rate for women in 2014 – 371 per 100,000 people
  • Louisiana was the only state in which the highest-income communities had the highest opioid-related hospitalization rate in 2014

The map, which includes information on 44 states and the District of Columbia, highlights data from AHRQ’s Fast Stats, an online tool that offers national and state-specific data on hospital stays and emergency department visits, including data by age, gender, community-level income and urban versus rural residency. The map is the most recent example of AHRQ’s ongoing efforts to address the nation’s opioid epidemic.

Prescription Opioid Use, Misuse, and Use Disorders in U.S. Adults

Prescription Opioid Use, Misuse, and Use Disorders in U.S. Adults: 2015 National Survey on Drug Use and Health


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Opioid-Related Deaths Might Be Underestimated: CDC


Death certificates from drug-linked infections may not label painkillers as possible cause

By Dennis Thompson

HealthDay Reporter

TUESDAY, April 25, 2017 (HealthDay News) — America’s prescription drug abuse epidemic may be even more deadly than expected, a new report from the U.S. Centers for Disease Control and Prevention suggests.

Some opioid-related deaths may be missed when people die from pneumonia and other infectious diseases spurred on by drug abuse. Their death certificates may only list the infection as the cause of their demise, explained CDC field officer Victoria Hall.

That means a number of drug-related deaths are not being counted, since surveillance systems mainly track overdose deaths.

“It does seem like it is almost an iceberg of an epidemic,” Hall said. “We already know that it’s bad, and while my research can’t speak to what percent we are underestimating, we know we are missing some cases.”

More than half of a series of drug-related unexplained deaths in Minnesota between 2006 and 2015 listed pneumonia as the cause of death, Hall and her colleagues found.

Twenty-two of these 59 unexplained drug-related deaths involved toxic levels of opioids. But the death certificates didn’t include coding that would be picked up by statewide opioid surveillance systems.

“We found if you have really profound infectious disease, like really bad pneumonia, that may be the only thing written on the death certificate. And thus it’s not going to get picked up in opioid surveillance,” Hall said.

Opioids killed more than 33,000 people in the United States 2015. That’s close to as many deaths caused by traffic crashes that same year, according to federal statistics. Nearly half of all opioid overdose deaths involved a prescription drug.

This spring, the Minnesota Department of Health learned of a middle-aged man who died suddenly at home, Hall said. Two days earlier, he’d seemed ill and was slurring his words, but refused his family’s pleas to go to the hospital.

“He was on long-term opioid therapy for some back pain, and his family was a little bit concerned he was abusing his medications,” Hall said.

Testing revealed that he died of pneumonia brought on by the flu, “but also detected a very toxic level of opioids in his system,” Hall said.

“However, on the death certificate it only listed the pneumonia, and it listed no mention of opioids, so this death wasn’t counted in the state opioid death surveillance system,” she said.

Opioid medications — codeine, hydrocodone (including Vicoprofen), oxycodone (Oxycontin, Percocet), morphine and others — can help bring on dangerous respiratory infections or make them even worse, Hall said.

“Opioids at therapeutic or higher than therapeutic levels can impact our immune system, actually make your immune system less effective at fighting off illness,” Hall explained.

The sedative effect of opioids also affects a person’s respiratory system, causing breathing to become slow and shallow, and making the person less prone to cough, Hall said — “making it easier for something like a pneumonia to really set in.”

A review of Minnesota’s unexplained death database revealed 59 cases with evidence of opioid use. Of those, 22 cases had not been reported to statewide opioid surveillance because the involvement of drugs hadn’t been listed on the death certificate.

Pneumonia was listed as a cause of death in 54 percent of the unexplained drug-related cases, the researchers found.

The Minnesota cases raise the question of whether similar drug-related deaths are being missed in other states, particularly those hardest hit by the prescription drug abuse epidemic, Hall said.

Dr. Robert Glatter, an emergency physician with Lenox Hill Hospital in New York City, said that emergency rooms “see a fair number of patients who use opiates. And in those patients we see, in general, a higher risk profile for developing pneumonia and other respiratory illness.”

The risk is even greater among drug users who smoke or have a respiratory ailment, such as asthma or COPD (chronic obstructive pulmonary disease), Glatter said.

“This is another in a sequence of reasons to not use opiates,” Glatter said.

“Physicians and all health care providers should be attuned to this risk of developing pneumonia, especially if they’re going to prescribe opiates. It’s another reason to proceed with extreme caution,” he noted.

The study results were presented April 24 at a CDC meeting in Atlanta.


Which Prescription Drugs Are Commonly Abused?

According to the National Institute on Drug Abuse, the three classes of prescription drugs that are often abused include:

How Do Opioids Work on the Brain and Body?

Since the early 1990s, doctors’ prescriptions for opioid medications — such as codeine and morphine (Astramorph, Avinza, Kadian, MS-Contin, Ora-Morph SR) — have greatly increased. That increase can be attributed to an aging population and a greater prevalence of chronic pain. Other drugs in this class include:

Cherokee Nation Sues Wal-Mart, CVS, Walgreens Over Tribal Opioid Crisis

Tops to prescription bottles are pictured inside the Wal-Mart pharmacy.

Robert Sullivan/AFP/Getty Images

The Cherokee Nation is suing top drug distributors and pharmacies — including Wal-Mart — alleging they profited greatly by “flooding” communities in Oklahoma with prescription painkillers, leading to the deaths of hundreds of tribal members.

Todd Hembree, attorney general for the Cherokee Nation, says drug companies didn’t do enough to keep painkillers off the black market or to stop the over-prescription of these powerful narcotics, which include OxyContin and Vicodin. “They flooded this market,” Hembree says. “And they knew — or should’ve known — that they were doing so.”

Walgreens, CVS Health, and Wal-Mart are all named in the suit, along with the nation’s three largest pharmaceutical distributors: AmerisourceBergen, McKesson, and Cardinal Health. They act as middlemen between pharmacies and drugmakers, distributing 85 to 90 percent of the prescription painkillers that some see as fueling a growing opioid epidemic in the U.S.

When reached for comment, one of the defendants, Cardinal Health, sent a statement to NPR saying the suit was a mischaracterization of facts and a misunderstanding of the law. “We believe these lawsuits do not advance the hard work needed to solve the opioid abuse crisis — an epidemic driven by addiction, demand and the diversion of medications for illegitimate use.”

But the Cherokee tribe says these companies regularly filled large, suspicious prescriptions within the Cherokee Nation’s 14 counties in northeastern Oklahoma. They also say the companies turned a blind eye to patients who doctor shopped and presented multiple prescriptions for the same medication. Oklahoma, where 177,000 tribal members live, leads the nation in opioid abuse. Almost a third of the prescription painkillers distributed in that state went to the Cherokee Nation.

“There are safeguards that are supposed to be followed — federal laws — that they turn a blind eye to because their profits are much more important to them,” Hembree says. “We were being overran by the amount of opioids being pushed into the Cherokee Nation.” A spokesperson for Walgreens told NPR the company declines to comment on pending litigation. CVS Health said in a statement, “We have stringent policies, procedures and tools to ensure that our pharmacists properly exercise their corresponding responsibility to determine whether a controlled substance prescription was issued for a legitimate medical purpose before filling it.” The other companies did not immediately respond to requests for comment.

Nowhere has the country’s opioid crisis hit harder than in Indian Country. Compared to other racial and ethnic groups in the U.S., American Indians have the highest rate of drug-induced deaths in the country. The use of OxyContin by American Indian high schoolers is double the national average.

The lawsuit estimates opioid abuse led to over 350 deaths within the Cherokee Nation between 2003 and 2014.

Cherokee babies are often born with an opioid addiction resulting from their mothers’ use of prescription painkillers throughout the pregnancy. Some spend their first moments on earth suffering through withdrawals. “They will have shakes, they will cry, and a lot of these children go on to have developmental and cognitive issues,” Nikki Baker-Limore, executive director of child welfare for the Cherokee Nation, says. “These children are born and they don’t even have a chance the second they come out of the womb.”

Several studies suggest high rates of addiction in Indian Country stem from the violence and cultural destruction brought down upon natives over the past 200 years. Because both trauma and resilience are remembered in our DNA, the genocide and forced removal of Cherokee and other tribes from their homelands by the U.S. government during the early 19th century has resulted in generational trauma.

Cherokee nation claims in the suit that drug companies are making money off of a vulnerable population and ignoring epidemiological and demographic facts. While this is the first time an Indian Nation has sued top drugs distributors and pharmacies, it’s not the first case of its kind in the country.

The city of Everett, Washington recently filed suit against Perdue Pharmaceuticals, the maker of OxyContin, for allowing its drug to saturate the black market. West Virginia, one of the hardest hit places in the nation’s opioid epidemic, settled with Cardinal Health for $20 million last year. Soonafter, the federal government slapped Cardinal Health and McKesson with multi-million dollar fines for failing to report suspicious orders of controlled substances to the Drug Enforcement Agency.

“Legal action is one of the only effective measures we have against pharmaceutical companies and distributors,” Adriane Fugh-Berman, an associate professor in the Department of Pharmacology and Physiology at Georgetown University, says. Fugh-Berman has served as an expert witness in several cases against pharmaceutical companies. “Companies don’t like lawsuits,” she says. “It’s a great way to get information into the public domain.”

But the Cherokee Nation’s lawsuit is different than other cases in a fundamental way: they filed it in tribal court. By doing so, lawyers for the Cherokee Nation say they hope to gain quicker access to internal corporate records. However, Hembree says they expect the defendants will file a motion to move the case into federal courts.

“We’re ready for that jurisdictional battle and we look forward to trying this case in Tahlequah, Oklahoma,” Hambree says, referring to the Cherokee Nation’s headquarters. The suit seeks billions of dollars in damages, and Hambree hopes it will help change the behavior of drug distributors and pharmacies.

“I can’t put Cardinal Health and McKesson and Amerisource in jail, but I can make them responsible for the damages they’ve incurred,” he says.

Even if the tribe is successful, Fugh-Berman says a change in behavior isn’t going to cure the opioid crisis in Indian Country and the U.S. in general. “It’s just one piece in this whole fabric of how to stop the opioid epidemic,” she says.

But curing that one piece could really make a big difference in the Cherokee Nation, according to Baker-Limore. She says the tribe has the infrastructure to provide recovery and rehab services. “Somebody needs to stop letting these opioids be so readily available,” she says. “We’re a small-town community. It’s hitting us hard.”

Nate Hegyi is a reporter for Montana Public Radio. Follow him at @natehegyi.

Sonoma County Heroin Overdoses Have Spiked Recently, Coroner’s Office Says

The Sonoma County Coroner’s Office says that suspected heroin overdose deaths in the county are up sharply over the past five to 10 days.

Sonoma County Heroin Overdoses Have Spiked Recently, Coroner's Office Says

SONOMA COUNTY, CA — The Sonoma County Coroner’s Office on April 25 said that there has recently been an upward spike in suspected heroin overdose deaths.

In the last five days, the Coroner’s Office has received nine deaths attributed to what we believe is heroin overdoses.

“While the final cause of death has yet to be determined and next of kins have not been notified, we want to share this information early to warn the public of this disturbing trend,” the coroner’s office said in a statement released to Patch.

All the deaths so far have occurred in the Santa Rosa area, the coroner’s office said, adding that there’s concern that the heroin being distributed in Santa Rosa right now is very volatile and potentially toxic.

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“All health, rehabilitation and treatment centers need to know that this substance is out there and any signs of overdose should be taken seriously,” the coroner’s statement read in part.

Anyone exhibiting signs or symptoms of an overdose should seek medical attention immediately or call 9-1-1, according to the Sonoma County Sheriff’s Office.

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