The Opioid Crisis

by Juliette F 

The ongoing opioid crisis in the United States started in the 1990s, and opioid overdoses have killed almost 600,000 people. This began with a rise in the amount of opioid prescriptions, leading to addiction and overdose in the 1990s. Prescription opioids include fentanyl and oxycodone. These are drugs that were regularly prescribed by doctors as painkillers from the 1990s, often to treat acute and chronic pain, as well as for cancer treatments. 

The body naturally produces opioids such as endorphins, and these help to naturally reduce stress and pain in the same way that oxycodone does synthetically. Opioid molecules bind to opioid receptors located in the brain and spinal cord, and trigger a series of intracellular events. Oxycodone specifically binds to mu receptors, which are the opioid receptors responsible for the analgesic effects of opioids. When opioid molecules bind to opioid receptors, the receptors release a G-protein(GDP) and bind to a different G-protein(GTP). This new inhibitory G-protein on the receptor, which in turn inhibits the production of an enzyme (adenylate cyclase), causing a decrease in cAMP molecules in a cell. This causes reduced neurotransmitter release, and altered ion channel function. Neurotransmitters are a chemical substance that transfer nerve impulses to other structures in the body. So when pain receptors are triggered, neurotransmitters are released and send signals to the brain so that you can feel pain. Calcium ions are crucial in the release of neurotransmitters, and reduced cAMP causes a reduction of the influx of calcium ions, which will prevent the release of neurotransmitters, creating a central nervous system (CNS) depression. Essentially, the brain functions slow down. This is then what stops patients from feeling pain as acutely. 

Addiction to opioids comes from the inhibition of GABA. When opioid molecules bind to mu receptors, they inhibit the production of the neurotransmitter GABA, which normally inhibits dopamine release. WIthout GABA, excess amounts of dopamine are released, causing surges of happiness or euphoria whilst taking the drug. Dopamine also reduces anxiety levels. These feelings of euphoria work in hand with the painkilling effect from the CNS depression to create an addictive and effective painkiller drug. Over time, the brain becomes less responsive to the drug, so bigger doses are required to get the same effect. Furthermore, the brain adapts to the use of the drug, and then finds that it cannot function without it, and the body experiences withdrawal symptoms such as sweating, nausea and anxiety when people attempt to stop taking the drug after becoming addicted. Opioid withdrawal is often seen as one of the worst feelings a person can have, and the need for the drug is extremely hard to overcome.

One of the most well known opioid prescription medications is OxyContin, sold by Purdue Pharma. OxyContin contains the semisynthetic chemical drug oxycodone, and first came on the market in 1996, generating over $35 billion in revenue over the next few years. It was advertised as being less addictive and analgesic (pain relieving) than morphine, so was prescribed to those with mild to serious pain, often from physical knee or hip injuries. It was seen as a solution for those with pain which wasn’t quite bad enough for morphine, but required some medication. 

US doctors are more likely to give prescription medication compared to other countries. This was a key factor in the rapid rise of addiction to OxyContin. This is for a number of reasons, starting with the lack of national healthcare. Patients are more likely to pay for medication to help with pain from a physical injury than pay to go to physical therapy for example, and it also requires far more paperwork and waiting time to go to physical therapy rather than get a prescription. Furthermore, the US allows adverts for prescription drugs on TV, which results in patients coming in and specifically asking for that drug. Other reasons include the historical lack of education on addiction given to general practice doctors, leading them to prescribe it without considering consequences. Finally, prescription drug companies (especially Purdue Pharma) frequently encouraged doctors to prescribe their medication, often through incentives.

In 2007, Purdue Pharma pleaded guilty to misleading the public about OxyContin’s risk of addiction. It was revealed that they published dubious scientific studies detailing that OxyContin was less addictive, when this was in fact, incorrect. At the time of FDA (food and drug administration) approval, it was believed that the controlled released formula would prevent an immediate high that would promote abuse of the drug. These Purdue Pharma studies detailed that the time release element of OxyContin made it less addictive and dangerous, however, the more potent pain relieving effects of oxycodone make it more addictive than morphine, despite being advertised as an alternative for less severe pain. Furthermore, people found that by crushing and snorting the drug, it could produce highs similar to heroin. As a result of the aggressive marketing and over prescribing by doctors, a very high number of people in the US found themselves addicted to oxycodone.

This result was especially prevalent and amplified in the rural areas of the US, including Tennessee, Kentucky and Virginia. The high proportion of manual labour intensive jobs in these states meant that plenty of people went to see doctors with hip or knee injuries, and their tendency to prescribe OxyContin for any mild to severe pain regardless of situation resulted in the widespread addiction that was seen in the 1990s. This addiction then led to an increase in overdoses on OxyContin as well, because higher doses of oxycodone cause an even bigger decrease in the release of neurotransmitters, causing breathing and heart rate to slow down.

If the opioid crisis interests you, then I recommend reading Empire of Pain to learn more about the Purdue Pharma fraud. Or if you are interested in the effects of the opioid crisis in the rural United States during the 1990s, then I recommend Demon Copperhead, which is the book that initially sparked my interest in this topic.