The Science Behind Why Opioids Are So Addictive

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Around 3400 B.C., humans began to cultivate the opium poppy in Mesopotamia. Since that time, humans have been using opiates as a treatment for pain and a variety of other health conditions.

Today, concentrated form of opiates (heroin) and synthetic human-made opioids (prescription painkillers, fentanyl, carfentanil) are the source of addiction for millions of Americans and are responsible for 91 overdose deaths every day.

Indeed, experts estimate that over 70% of the world’s opium supply is used for the production of heroin, and at least 17 million people globally used opium, morphine, or heroin in 2016. But why exactly, are these drugs so addictive? How do they hijack the brain so efficiently?

Two Types Of Pain

Well, first of all, there are two kinds of pain – peripheral and central pain. Peripheral pain is a result of damage to your skin or muscles, such as burns.

Pain fibers detect these injuries and transmit the signal to nerve cells (neurons) in the brain and spine, the two main components of the central nervous system.

Conversely, central pain is a manifestation of your mind’s perception of the severity of the injury.

Our bodies produce natural opioids called endorphins. Endorphins relax pain nerves. Typically, pain fibers collaborate with the body’s central nervous system, and hormones that reduce stress are released as a result. Also, the immune system responds to inflammation as it occurs. However, things don’t always go as planned when these pain pathways become overloaded or disconnected.

Just One Receptor

For example, imagine you have chronic pain in your lower back. The muscles suffer from inflammation and are continually transmitting pain signals to your brain. Your naturally-produced opioids are no longer doing the job required to ease the pain, so you visit your doctor, and she prescribes you a painkiller such as OxyContin.

Chemical messengers called neurotransmitters are “caught” by most types of receptors and activate nerve cells, initiating electric pulses that transmit the signal forward. Both endorphins and prescription painkillers land on tiny receptors at nerve endings, but these receptors work in reverse. Instead, they block electric pulses from transmitting to nerve cells.

Opioids bind to three receptors, Mu, Kappa, and Delta. But is it Mu that is responsible for most of the effects of opiates, regardless of whether they are legal or illicit.

These receptors also initiate widespread effects because they regulate other areas in the brain besides pain pathways, and result in additional actions such as decreased respiration, alertness, and blood pressure.

Addiction is triggered in the mid-brain, where opioid receptors turn off a group of nerve cells known as GABAergic neurons. These neurons function as an “off-switch,” if you will, for the networks in the brain responsible for feelings of pleasure and euphoria.

So in layman’s terms, opioids turn off the off-switch and block GABA neurons which typically ensure that the brain’s reward center isn’t inundated with dopamine.

So, when the GABA neurons are turned off, pleasure circuits are filled with dopamine, an effect which in turn initiates a rush of happiness. Once dopamine enters the amygdala, it mitigates stress and anxiety.

These actions reinforce the idea that opioids provide a reward, and the brain wants to do it again. And again. If it the brain continues to be fed, use of the drug becomes habitual.

The Downward Swing


Once a person’s body adapts to drug use, addiction begins to set in full-throttle. GABA neurons and other nerves still want to transmit messages, so they start to adjust.

In response, they release at least three times more cyclic AMP, a compound that readies the neurons to fire electric pulses.

This switch now causes opposite effects, such as increased blood pressure, anxiety, and dysphoria. As these adverse effects enter the prefrontal cortex, the desire for opioids is further enforced. Other substances, such as alcohol, also trigger addiction via the brain’s pleasure center, but it is the wave of withdrawal effects that make opioids so hard to escape.

Treatment: Harm Reduction Is Often The Answer

As opioid addiction progresses, the person requires more and more of the drug to avoid withdrawal symptoms and may result in overdose if so much of the drug is used that the brain slows breathing until it stops altogether.

This is why medication-assisted therapy is so popular. In opioid replacement therapy, less-potent medications such as Suboxone are used in place of more addictive and dangerous drugs such as heroin. These medicines land on opioid receptors and shield them from heroin, but do not activate them in the same way.

This action reduces the likelihood of an overdose, and less-addictive opioid replacement drugs attach to the receptor for a longer period, thus reducing withdrawal symptoms.

However, no treatment is perfect, and some patients may have to remain on the replacement drugs for extended periods, even years.

And then, as with any opioid-based medication, there remains a risk of misuse (except for injections), and many criticize the approach as trading one drug for another. But still, when used in combination with counseling and cognitive-behavioral therapy, so far, it’s the best we’ve got.

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