Prescription Opioid Addiction –Factors Driving the Epidemic

Updated: Feb 18


DUNCAN VAN NEST, BS

ASIF ILYAS, MD, MBA, FACS


SUMMARY POINTS


  • Opioids receptors are located throughout the body and are activated by natural neurotransmitters known as endorphins, also known as endogenous opioids, effecting the body’s ability to modulate pain, respond to emotion and stress, and perceive pleasure.

  • Exogenous opioids (such as oxycodone, morphine, heroin, etc) also stimulates the body’s opioid receptors throwing off the body’s normal balance and desensitizing opioid receptors requiring more opioids to achieve the same level of response.

  • With increasing exposure to opioids, the greater amount and frequency is needed by the body for the opioid receptors to achieve the same level of response thereby increasing tolerance and driving craving.

  • Poor understanding, low quality early research, and misleading advertising has led medicinal opioids to expand in utilization and result in widespread opioid use, dependency, and abuse.


ANALYSIS


The reasons for the widespread abuse of prescription opioids and opioid addiction over the past few decades and the resulting opioid epidemic are complex and multifaceted. At a fundamental level, the prescription opioid epidemic can be explained the overwhelming tendency for opioids to result in dependence. That basic tendency towards dependency mixed with either misinformed or misunderstood views of patients and providers about the dangers of prescription opioids has made opioids ripe for dependency and abuse. However, by educating patients and providers about the science of opioid dependence and addiction, we can continue to help inform the public about the dangers of prescription opioids, encourage evidence-based prescribing guidelines, and take steps towards mitigating the opioid epidemic.


Opioids receptors are located throughout the body and are activated by neurotransmitters and hormones such as endorphins, also known as endogenous opioids, that our body produces naturally. Activation of these receptors in certain areas of the brain result in pain modulation, emotional responses to pain and stress, as well as perception of pleasure and well-being.1 Endogenous opioids are released in response to pain and stress and they serve to help us better tolerate these situations when we encounter them in our daily lives. Additionally, these substances are released during pleasurable activities and act on the reward centers of the brain to reinforce adaptive behaviors such as feeding, drinking, exercise and sexual activity. This fine-tuned balance helps us to tolerate stress and encourages us seek out pleasure and promote well-being. However, this balance can be easily disrupted.


Exogenous opioids are substances that effect opioid receptors that are not naturally produced by the body. Exogenous opioids include substances such morphine, heroin, and oxycodone, among others. Exogenous opioids, when introduced into the body, can quickly throw the natural opioid system out of balance. Exogenous opioid concentrations in the bloodstream are often much higher and more potent than what occurs naturally. If these concentrations are sustained for extended periods of time, the receptors in the brain become desensitized. As a result, higher and higher concentrations of opioids are required to achieve the same effect of pain relief and pleasure (FIGURE 1).2 At the same time, opioids are acting on the reward centers of the brain causing reinforcement of opioid consumption and driving cravings. Tolerance and craving are the first stages of addiction. Opioid dependence follows at which point continual opioid consumption is needed to prevent the undesirable symptoms of withdrawal, furthering strengthening the addictive effects.



The addictive effects of opioids have been recognized for centuries, but the medicalization of opioids have given the false sense that these drugs are safe and without significant risk. In fact, heroin was introduced by Bayer in 1898 and was quickly deemed a wonder drug. It was marketed as a nonaddictive treatment for severe cough and was later approved for general use in 1906 by the American Medical Association.3,4 However, the addictive and harmful effects of heroin were quickly realized. Patients treated with heroin for extended periods of time required increasing amounts of the drug, almost uniformly developed addiction and driving efforts to procure the drug via illegal means. This ultimately led to the ban on heroin in the United States in the mid 1920s.




The modern prescription opioid epidemic closely mirrors the heroin epidemic of the early 20th century. Opioid analgesics were used throughout the 20th century in other forms for acute pain and cancer pain. Beginning in 1987 with the approval of MS Contin by the FDA, pharmaceutical companies started marketed longer acting opioids as less addictive than their historical counterparts (FIGURE 2). In 1995, Oxycontin was approved for the treatment of acute and chronic pain.5 Because they were promoted as safe and effective treatments by the medical community, perceptions of these drugs were seen much differently than other opioids like heroin, now ubiquitously viewed as a dangerous street drug.6 While these modern opioids were “clean” in that they were manufactured under strict regulations, they still served to hijack the natural opioid system in the same way as other exogenous opioids.


While opioid formulations, prescription practices, and public perception of opioids have changed over the past several decades, the overwhelming propensity of opioid drugs to result in tolerance, dependence and addiction has remained unchanged. It is crucial that patients and their providers understand the science behind opioid addiction and recognize the dangers of prescription opioids. Opioid medications still serve a role for the treatment of acute pain and cancer pain. However, standard opioid medications for chronic pain are often inappropriate. Long term opioid efficacy is limited by drug tolerance and the potential for abuse and misuse outweighs the potential for benefit. Strict adherence to prescription guidelines must maintained by providers, and we must educate the public about the dangers of prescription opioids or else we risk perpetuating and prolonging this deadly epidemic.



REFERENCES:

1. Volkow ND, McLellan AT. Opioid Abuse in Chronic Pain — Misconceptions and Mitigation Strategies. New England Journal of Medicine. 2016;374(13):1253-1263. doi:10.1056/NEJMra1507771

2. Martyn JAJ, Mao J, Bittner EA. Opioid Tolerance in Critical Illness. New England Journal of Medicine. 2019;380(4):365-378. doi:10.1056/NEJMra1800222

3. Bulletin on Narcotics - History of Heroin. United Nations : Office on Drugs and Crime. Published 1953. www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1953-01-01_2_page004.html

4. Glyco-Heroin-(Smith). Historic Medical Library of the College of Physicians of Philadelphia. https://www.cppdigitallibrary.org/items/show/6760

5. Timeline of Selected FDA Activities and Significant Events Addressing Opioid Misuse and Abuse. FDA. Accessed September 6, 2020. https://www.fda.gov/drugs/information-drug-class/timelineselected-fda-activities-and-significant-events-addressing-opioid-misuse-and-abuse

6. Crowe K, 2018. New questions about old Canadian study foreshadowing opioid crisis. CBC News. Published June 2, 2018. https://www.cbc.ca/news/health/second-opinion180602-1.4687687



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