For many years, health care providers like me were told that we were undertreating pain and that pain was a vital sign that needed to be measured. Concurrently, we were reassured that opioids were a safe and effective way to treat pain, with very little potential for development of abuse. As a result, opioid prescriptions in the United States skyrocketed. A common way to compare opioids is to calculate their strength relative to morphine, called morphine milligram equivalents, or MMEs. In 1992, our country dispensed 25 billion MMEs of prescription opioids; by 2011, that number had reached 242 billion. Meanwhile, opioid-related deaths and treatment admissions increased in parallel.
In the 1990s, the number of opioid prescriptions written for people undergoing surgery or experiencing pain conditions grew — and so did related problems. As a result, “We are in a current opioid epidemic, with 91 substance-related deaths each day, according to the CDC,” says Dr. Elizabeth Matzkin, an orthopedic surgeon and assistant professor at Harvard Medical School.
Most people think they know what substance misuse looks like. Maybe it’s an uncle who drinks so much at family gatherings that he stumbles around and tells inappropriate jokes. Or it’s a friend who started smoking marijuana in college and didn’t quit when she “grew up.”
The medical community has typically thought of addiction as abuse of a substance that continues even when there are detrimental consequences, such as losing a job or developing physical issues like kidney damage or ulcers.
Chemical dependency is broader and may include other physical signs like an increasing tolerance to the substance, or withdrawal symptoms when someone tries to quit or cut down on using it. It also includes emotional, social and psychological factors.
Drugs of abuse, including opioids, act on the brain’s reward system, a system that transfers signals primarily via a molecule (neurotransmitter) called dopamine. The function of this system is affected by genetic and environmental factors. For example, a recent study published in the scientific journal PNAS revealed one of those genetic factors. Researchers demonstrated that a type of small infectious agent (a type of RNA virus called human endogenous retrovirus-K HML-2, or HK2) integrates within a gene that regulates activity of dopamine. This integration is more frequently found in people with substance use disorders, and is associated with drug addiction.
We now know that the function and dysfunction of the brain’s reward system is complicated, plastic (undergoes changes based on negative and positive factors), and involves complex interactions of genetic and environmental factors. Alterations in gene expression can lead to changes in the function of the brain’s reward system, so a person is more or less likely to self-administer drugs. Together this knowledge can ultimately lead to the development of multilevel and more efficient prevention and therapeutic approaches to address the ongoing opioid epidemic.
n the June 14th Wall Street Journal, Johns Hopkins University bioethicist Travis Rieder, in an excellent essay, shared with readers his battle with pain resulting from a devastating accident, the effectiveness of opioids in controlling the pain, and the hell he went through when he was too rapidly tapered off of the opioids to which he had become physically dependent.
The aggressive schedule launched me into withdrawal, and I learned viscerally, firsthand, what the absence of opioids can do to someone whose brain has become accustomed to them. Those symptoms include increased sensitivity to the very pain that the opioids counteract, as well as extreme flu-like symptoms, insomnia and crippling depression. I came to understand why people sometimes go back onto deadly dangerous drugs: because the alternative is such profound suffering that it makes you want to die.
~ Travis Rieder
We learned that the 2017 drug overdose numbers reported by the US Centers for Disease Control and Prevention clearly show most opioid-related deaths are due to illicit fentanyl and heroin, while deaths due to prescription opioids have stabilized, continuing a steady trend for the past several years. This would more likely be termed “Fentanyl Crisis” rather than “Opioid Crisis” to describe the situation, because it more accurately points to its cause—nonmedical users accessing drugs in the dangerous black market fueled by drug prohibition.
The CDC guidelines do not explicitly say patients should never exceed 90 morphine milligram equivalents a day, but they do suggest that such doses are hard to defend. “Clinicians should use caution when prescribing opioids at any dosage,” the CDC says, and “should carefully reassess evidence of individual benefits and risks when considering increasing dosage” to 50 MME per day or more. The guidance adds that doctors “should avoid increasing dosage” above 90 MME per day, or at least “carefully justify a decision to titrate dosage” above that level.
Although the CDC implies there is something special about these numbers, the study of opioid-related deaths in North Carolina found that “dose-dependent opioid overdose risk among patients increased gradually and did not show evidence of a distinct risk threshold.” Critics see the CDC’s cutoffs as arbitrary, since patients vary widely in the way they metabolize and respond to opioids, especially if they have developed tolerance after years of treatment.