OPIOIDS AND THE EVOLVING EPIDEMIC OF ADDICTION IN AMERICA
Mark S. Gold, MD and Drew Edwards, EdD, MS
Mark S. Gold, MD and Drew Edwards, EdD, MS
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Opioids and the Evolving Epidemic of Addiction in America
Mark S. Gold, MD and Drew Edwards, EdD, MS (https://www.counselormagazine.com/author/mark-s-gold-md) • January 3, 2020
The current opioid crisis in the US is a social and public health nightmare. Both the inherent and new challenges are vexing, formidable, and overwhelming our social, health care, and legal systems. Questions surrounding legitimate opioid use, pain management, so called “recreational abuse,” and life-threatening opioid addiction is an ever evolving and moving target. The unprecedented rise of mortality, trauma, disability, infectious disease (Klevens, Hu, Jiles, & Holmberg, 2012), and debilitating comorbid psychiatric conditions are expected sequala of addiction, while altering the life trajectories of millions of children and adolescents who are routinely exposed to addictive substances. Not surprisingly, the media frenzy and political hyperbole is squarely aimed at the usual low-hanging fruit: Big Pharma and overprescribing and medical mismanagement by alleged “bad doctors,” even those who prescribe opioids for their legitimate, long-suffering malignant pain patients (Gold & DuPont, 2018). Clearly, we need new pain treatment options, but physicians have to work with the medications and interventions that are currently available to help their patients.
But, do we just have an opioid epidemic? We do have a crisis in opioid overdoses, but even in these cases, some are suicides and many are polydrug overdoses with opioids as one of several drugs.
It is shortsighted and tactically ineffective to narrow our gaze solely on opioids—particularly prescription opioids. The opioid crisis moved from prescription painkillers, with pharmaceutical quality control and known dosing, to cheap heroin, adulterated with potent illicitly manufactured fentanyl. Recently enacted federal policies limiting the production and availability of pharmaceutically produced opioid medications may be politically expedient but expecting this action to reign in any illicit opioid use, addiction, or mortality is fanciful nonsense, as the evidence clearly shows. You cannot employ a static remedy to a rapidly evolving problem (Gold & Edwards, 2018).
Shutting Down the Pill Mills
Shortly after the turn of the century, a highly concerted collaboration between the Drug Enforcement Administration (DEA), local law enforcement, and public health ofcials were successful in shutting down overprescribing pill mills, which were de facto drug distributors. Innovative federal and statewide policy changes were enacted that now monitor and report the prescribing practice of every physician, on all patients who are prescribed any scheduled medication. This action effectively lifted the veil on the covert prescribing behavior of unscrupulous practitioners. This was an important effort but did not appear to curtail the opioid epidemic. A longer-lasting effect of this effort was to change the burden of opioid monitoring from resting solely on the shoulders of good, ethical, and overwhelmed physicians. These new policies successfully shifted some of the
monitoring responsibility to the point of purchase at the local pharmacy. Moreover, pharmacists are legally liable for what they dispense (“America’s pill,” 2019; Christie et al., 2017).
As a result of these legislative and law enforcement interventions, the cost of doing business for the pill mills and high prescribers became prohibitive. However, opioid use and mortality continued to increase in record numbers. For instance, between 2015 and 2016, long after the heyday of the pill mills, annual mortality from opioid overdose climbed to an unprecedented sixty thousand deaths (Hedegaard, Warner, & Miniño, 2017). In addition, drug overdose has become the number one cause of death for Americans under the age of fifty. Data from the Florida Drug-Related Outcomes Surveillance and Tracking System reveal that more than 90 percent of opioid overdose deaths in 2016 showed other drugs of abuse present at the time of death. How many? The average was two to four, but as many as eleven were present during postmortem evaluation in many of the deceased (Pitt, Humphreys, & Brandeau, 2018).
Opioids, like other drugs of abuse, target the brain’s reinforcement centers to produce euphoria. Chronic use leads to dysphoria, anhedonia, and craving. Addiction to opioids often produces anxiety, insomnia, depression, and agitation, which addicts routinely self-treat with marijuana, sedative hypnotics drugs such as alcohol, benzodiazepines, or potent sleep preparations. The combination of opioids and sedative hypnotic drugs increases the risk for overdose mortality significantly as both classes of drugs effect the autonomic nervous system located on the brainstem—the human autopilot that controls essential functions such as breathing and heart rate. In the majority of fatal overdoses, addicts use a sedative hypnotic drug to help them sleep—or more accurately “pass out”—and they become so sedated, that they simply stop breathing, which stops their heart within a few minutes . . . and they never wake up. Some overdoses are accidental, and others are the result of wishing you might die, or not caring if you die. Our clinical experience suggests that some of these drug combination overdose deaths are likely suicides due to intense shame and feelings of utter hopelessness (Hedegaard et al., 2017).
After the pill mills were effectively shut down, why did mortality from opioid overdose increase so dramatically? It is because addicts simply changed the drugs they took and where they got them. They switched to heroin or bought opioids on the street and the results were disastrous. Surveillance data revealed that the sevenfold increase in overdose mortality was directly attributed to the use of synthetic, illicitly manufactured opioids—namely fentanyl and its cousins (O’Donnell, Halpin, Mattson, Goldberger, & Gladden, 2017). The cheap, easy-access heroin was cut with Chinese and Indian fentanyl. Please note that these data exclude overdose deaths from the synthetic opioid called methadone (CDC, 2018).
There is no analgesic or opioid more potent, faster acting, and more addictive than the fentanyl family of drugs. Fentanyl, a lipophilic substance was originally FDA-approved as a short-acting analgesic for use in surgery. Because it is lipid soluble (i.e., increasing is absorption and bioavailability) and approximately one hundred times more potent than morphine, simply touching it can be lethal. Its big brother, carfentanyl, is ten thousand times more potent that morphine. Other fentanyl cousins include acetyl-fentanyl and furanyl, all of which are being manufactured by amateur chemists in their garages or basements (NIDA, 2018). The best available evidence reveals that cheap, illicitly made fentanyl is responsible for the surging mortality prevalence observed in 2016 to 2017 (Jones, Einstein, & Compton, 2018). It is difficult for average citizens to fully comprehend the potency of this drug. Only one microgram of fentanyl is needed to produce analgesia in humans, and a microgram (μg) is one-millionth of a gram (gm). If an amateur chemist overshoots the calculation by an infinitesimal amount, death by overdose is a certainty (O’Donnell et al., 2017).
Why Are People Using Such a Dangerous Drug?
In short, people are using these drugs because they are cheap, widely available, and drug economics. The cost of manufacturing fentanyl is a mere fraction compared to the cost associated with producing and selling heroin. Consider the steps:
1. Farming poppy plants in Asia
2. Extracting and processing the thebaine and codeine
3. Converting the raw product into heroin
4. Smuggling the heroin out of Asia and into the US
5. Distributing the product to thousands of dealers in the US
6. Collecting the money
7. Laundering the money
When the pills shut down, the cost of illegally attained prescription opioids tripled (Cicero, Ellis, Surratt, & Kurtz, 2014). The addicts migrated to the easily accessible, low cost heroin, often cut with fentanyl. The same market forces are now driving addicts away from heroin to use illicitly manufactured fentanyl, as it is much cheaper than old-fashioned street heroin as well as the new street heroin laced with fentanyl. As we analyze the trend, it is going to get much worse (Pergliozzi, LeQuang, Taylor, & Raffa, 2018). Globally produced, synthetically manufactured opioid analogs are easy to make, easy to conceal, easy to distribute, cheaper to buy, and thus, will be used by more people, producing more addiction and more mortality. In these phases of the current opioid epidemic it is important to keep in mind that prescription opioids, from pills mills and script MDs, involved legal, FDA-approved medications—doses or purity of opioid pill was not a question. Once the epidemic morphed from prescriptions to illicit drugs, the dose and purity became major issues. Add fentanyl, other drugs of abuse and other impurities and the likelihood of death, disability, and disease increases.
The Bigger Picture
What has been largely ignored in the so-called “opioid crisis,” is the powerful undertow of early exposure to drugs of abuse as teens or young adults set the stage for future use, abuse, and dependence. Mothers increasingly expose their offspring to alcohol, tobacco, marijuana, and other drugs in utero and in early life. The brain changes in response to these exposures, making drug use and dependence more likely “recreational” drug use, binge drinking, and the unprecedented use of marijuana, made available via ballot-box initiatives rather than the FDA. Rather than proving safety and efficacy for a specific medical diagnosis, via double-blind, placebo-controlled studies, like we are doing for ketamine as a treatment for depression, marijuana was simply voted to be “medicine” without the benefit of scientific scrutiny regarding its safety and potential efficacy. As a result of marijuana legalization, competitive free-market forces demanded production of highly potent marijuana products.
Why are these other drugs important to the opioid discussion? Most opioid overdose death autopsies reveal poly drug use. Alcohol, marijuana, and other drugs are found alongside heroin and fentanyl. Recent findings by the National Institute on Drug Abuse (NIDA) show that adolescent marijuana users are 2.6 times more likely than nonusers to use opioids (2017). With this association in mind, consider that in the US eight thousand people per day, mostly adolescents and children, will use their very first addictive substance (NIDA, 2017). Of these, seven thousand will use highly potent marijuana. The evidence shows that early initiation is associated with a twofold increase in the prevalence of addiction compared to those who delay initiation until age eighteen or above (Olfson, Wall, Liu, & Blanco, 2018). Specifically, 18 to 20 percent of early-initiated teens will become addicted via marijuana and/or alcohol, and of these most will quickly progress to stronger and faster-acting intoxicants as neuroadaptation and tolerance compels them (Compton et al., 2019). Consider the treatment implications of early initiation: for example, a twenty-four-year-old presents as using heroin or fentanyl daily, but he or she has used numerous drugs and been “addicted” for ten years. This is tantamount to treating patients who present to oncologists with stage-four cancer; the treatment options are very limited, and the survival rate is very low. A viable public health and prevention goal would be to delay the age of initiation to at least eighteen years old. According to current data, this would reduce the prevalence of addictive disease by 50 percent.
The opioid crisis is best thought of as part of the larger, continuously evolving drug epidemic in America. The foundation of which is societal sanctioning of teenage recreational pharmacology that has resulted in the aggressively marketed and widespread use of intoxicants that, by design, hyperactivate the brain’s reward biology, producing measurable neuroadaptations and acute changes in neuro-connectivity as well as the subjective experience of pleasure. Simply stated, all drugs of abuse (including alcohol) stimulate their own taking by producing an intense, short-lived, and highly pleasurable experience that exceeds what could be experienced naturally. Specifically, the human reward system is a complex, sequential interaction among specific neurotransmitters, neuropeptides, and hormones that mediate our emotional and mental state (Baler & Volkow, 2006).
However, exogenous synthetic opioids bind to opioid receptors mu (μ), kappa (κ), and delta (δ) and usurp neural signal transmission (Narita, Funada, Suzuki, 2001; Zhu, Rockhold & Ho, 1998). Opioid receptors are found in both the central and peripheral nervous system (Zhang, Kranzler, Yang, Luo, & Gelernter, 2008). Opioids are distributed throughout the brain in varying concentrations depending on their classification, however they are found to be highly abundant in the amygdala, the hippocampus, and the caudate putamen (Filliol et al., 2000). These areas, as well as the ventral tegmental area, contain interneurons that compose the complex neural circuitry involved in opioid dependence. Opioid receptors differ in their affinity to bind with specific ligands to induce varying degrees of analgesia and anti-nociception, in addition to numerous physiological effects (Cowan, Zhu, Mosberg, Omnaas, & Porreca, 1988). Endogenous opioid peptides, including enkephalins, β-endorphins, endorphins and dynorphins, are mediated by binding to opioid receptors and therefore play a role in modulating mood and regulating stress responses (Blum et al., 2014b).
The primary neurotransmitters involved in brain reward include: Dopamine, endogenous opioids, gamma amino butyric acid (GABA), norepinephrine, and serotonin (NIDA, 2018). Although the etiology of addiction is not well elucidated, we have discovered phenotypical risks factors rooted in the accumulation of single nucleotide polymorphisms (SNPs), which are genetic variations found in our DNA (Blum et al., 2015) of which some increase the risk for reward deficiencies. These heritable deficiencies can be provoked and manifest as a result of social and environmental stressors or simply by experimentation with mood-altering substances (Blum et al., 2008). Reward deficencies include addictive diseases, depression, anxiety, stress disorders, PTSD, hedonic overeating, and obesity.
Numerous SNP’s have been identified and to a large extent sequenced and codified (Blum et al., 2014a). Through novel genetic testing they can be identified and used to determine relative risk for addiction and related concurrent conditions involving reward deficiency. As a result, users erroneously feel that they have done something of importance, because their brain misinterprets the drug- induced euphoria as evidence of accomplishment that should be repeated frequently. In other words, newly initiated drug abusers conclude, “If I feel this good, my life must be good.” This is how addiction reprioritizes the brain to become narrowly focused on reward via continued drug use. As a result, families, friends, health, jobs, and other important remnants of addicted people’s pasts are increasingly diminished and appear to move to the periphery of importance in their lives (Li et al., 2015). Treatment and recovery should be narrowly focused on reversing this.