February 28, 2023, by mbzva

The highs and lows of opioid use: learning from the north American opioid epidemic

By Ryan Duffy, 4th Year Neuroscience MSci

Opioids are a class of drugs that interact with the endogenous opioid system, to either activate or deactivate its impact on bodily sensations or psychological states. Endogenous means that our body must make compounds that activate this system, and indeed they do. Endorphins is one of the major opioids released from the body, and many studies believe it is the compounds that leads to “runners high”, as endorphins are release during physical activity (1). Learning about the interconnectivity of the endogenous opioid system, neuroscientists found compounds that we don’t make naturally that can also activate opioid receptors. The major opioid drug used in hospitals around the world, morphine, was first isolated from opium in the early 1800’s and it was quickly introduced into clinical practice.

The main function of opioids is in a pain killer, and it remains the most effective pain killer to date. Morphine works by activating opioid in the central nervous system (brain and spinal cord) and the peripheral nervous system (nerves). When they activate this receptor, they “turn off” neurons, and prevent their activity, making morphine a central nervous system depressant. Turning off the nervous system is an incredibly effective pain-relieving tool as it prevents the nerves from conducting painful signals to the brain, meaning, no “pain” can be perceived.

With all drugs there is normally an equal exchange between value and side effects, and morphine is no different. Because morphine is so good at shutting down neuronal activity, if too much is used, we can start to shut down processes that we want to keep “on”. The most common of these processes is breathing, more specifically contraction the muscles we use to breath. Because morphine relaxes the nerves so much it can prevent the automatic breathing process that is normally taken care of by the brain when we fall asleep. This leads to a condition called respiratory depression, and it the most common cause of death associated with opioid overdose (2).

Not only do opioids have serious side effects, but they are also highly addictive. One of the reasons for this is because they activate the brains “reward pathway”. By activating the reward pathway, we can significantly increase in dopamine, which is a chemical that is thought to regulate emotion, motivation, and reward. When the drug wears off, we also lose the dopamine that it increased, and we also see that dopamine goes below baseline as the body doesn’t produce as much as it normally would in healthy conditions. This lowering in normal dopamine is theorised to be one of the reasons why psychological withdrawal occurs and addiction begins (3).

Because of these addictive qualities opioid based medications have become drugs of abuse, particularly in north America, where many experts are terming mass opioid abuse as a epidemic. In the US 3,000,000 citizens suffer from opioid use disorder, with 500,000 of these being addicted to heroin. With these statistics being so profound, should be thinking about altering opioid use to treat pain?

One problem that has been identified by experts is the over reliance on opioids to treat mild to moderate pain, in combination with a lack of transparency from drug companies regarding the addictive qualities of opioids. The first drug to light the fuse on the epidemic was called Oxycodone (OxyContin), a semi-synthetic opioid that was initially intended to be used a pain killer for moderate pain like a migraine. The problem with this drug was that it was described and sold to doctors as non-addictive, and advertising campaigns signalled that the drug had a less the 1% addiction rate. Because of this, doctors were more willing to give OxyContin to patients as a first line pain killer, as it was effective and “non-addictive”. It soon came out that OxyContin was much more additive and dangerous than first imagined, in fact, it was found that OxyContin was just as addictive as other opioid medication like morphine. Because of this, patients that took OxyContin regularly became addicted to opioids. With continued use their tolerance grew too, meaning they needed a higher dose to achieve the same pain-relieving effect, which is another common side effect of opioids. Because of the price of OxyContin many users couldn’t afford to increase their dose and they swapped to other opioids that were cheaper like heroin or fentanyl, to reach the same concentration and therefore the same pain relief (4).

Suggestions to rectify this situation have included education to aware healthcare professionals and patients of the dark side of opioids, in an attempt to prevent over prescription and abuse. The enhancement of non-opioids drugs as first as painkillers and the use of opioids is reserved for severe pain.

Although a lot of damage has been done with these drugs, it is important to be hopeful and use these tragedies as lessons for the rest of the world. Implementing these as standard procedures before it becomes a worldwide opioid pandemic.


  1. Hicks SD, Jacob P, Perez O, Baffuto M, Gagnon Z, Middleton FA. The Transcriptional Signature of a Runner’s High. Med Sci Sports Exerc. 2019 May;51(5):970–8.
  2. Baldo BA, Rose MA. Mechanisms of opioid-induced respiratory depression. Arch Toxicol. 2022 Aug;96(8):2247–60.
  3. Kosten TR, George TP. The neurobiology of opioid dependence: implications for treatment. Sci Pract Perspect. 2002 Jul;1(1):13–20.
  4. Kibaly C, Alderete JA, Liu SH, Nasef HS, Law P-Y, Evans CJ, et al. Oxycodone in the Opioid Epidemic: High “Liking”, “Wanting”, and Abuse Liability. Cell Mol Neurobiol. 2021 Jul;41(5):899–926.




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