How the Opioid Epidemic Evolved
Opioid history:
Our understanding of the natural opioid system is relatively new as it wasn’t thoroughly defined until the 1970’s. Yet, the use of opioids far predates our current lifetime. In fact, radiocarbon dating revealed opium poppy was found nearly 12,000 years ago in the settlements of early humans. 8,000-year-old opium prescriptions were discovered carved into clay tablets. It wasn’t until 1803 that morphine was isolated from opium resin. This was the first of many opium derived compounds termed “opioids”. Despite millennia of use, knowledge of substances was restricted to only the physical effects exhibited by the user. The current knowledge landscape is astronomically further developed by comparison.
Current Understanding:
Opioids act on the opioid receptors consisting of three main subtypes: mu, kappa, delta. Each receptor has its own distribution pattern in the brain, unique effect, and a shared effect common across the subtypes. For instance, mu receptors of the basolateral amygdala and nucleus accumbens, two components of the brain reward system, produce the characteristic feelings of euphoria. Meanwhile brain delta and kappa receptors manifest anti-anxiety and dysphoric feelings respectively. Clinically, opioid drugs primarily act at mu receptors and are used to manage severe acute and/or post-operative pain, chronic pain, diarrhea, and coughing. While possessing therapeutic potential, these medicines have some life-threatening side effects. Physicians need to seriously weigh the benefits and risks before administration.
The Epidemic:
From 1999 to 2020, the number of yearly overdose deaths due to prescription opioids increased nearly fivefold. Over 560,000 people have died since the epidemic started. Until 2020, majority of these deaths were caused by prescription opioids alone. A catalyst to the start of the opioid epidemic was Purdue Pharma’s Oxycontin, which gained FDA approval in 1995. Oxycontin was designed to be taken every 12 hours, with the thought that slow release over time would be safer. However, the recorded number of people abusing Oxycontin went up from 400,000 in 1999 to 2.8 million in 2003. Furthermore, the FDA went on to issue a warning to Purdue Pharma citing misleading advertising.
In the following years, awareness of the opioid epidemic grew substantially with Kentucky filing a state level lawsuit against Purdue Pharma in 2007. By 2015, a series of lawsuits caused Purdue Pharma to significantly decrease their promotional spending targeting prescribing doctors. Instead of deterring competitors, it caused them to spend even more money targeting doctors in hopes of capitalizing on Purdue Pharma’s decline.
By the late 2010s, the FDA started mandating a black box warning for immediate release opioids. It also issued guidance on emphasizing the abuse-deterrent properties of opioids combined with anti-abuse agents. In 2020, the FDA required all producers of opioid drugs to add recommendations for naloxone, a lifesaving drug that stops overdoses, to the prescribing information. The increased focus on the opioid epidemic improved things as most deaths by overdose are now due to non-prescription opioids as of 2020.
Conclusion:
For thousands of years, humans have known about the therapeutic potential of the opium poppy plant. Opioid medication takes advantage of a naturally existing receptor system and can be beneficial. However, these medicines are highly addictive and can have fatal side effects. Pharmaceutical companies have a responsibility to put warnings on labels and give information on overdose prevention. Doctors have a responsibility to critically weigh benefits versus risks and prescribe naloxone along with opioid medication upon the slightest suspicion of addiction potential. Hundreds of thousands of people have lost their jobs, homes, families, and even their lives since the opioid epidemic began. Only recently, have prescription associated deaths dropped below that of recreational opioid use. This illustrates how grave the consequences are when opioids are given out without care. Hopefully, we learned our lesson and will continue to be vigilant regarding opioid administration going forward.
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