How Is The Brain Impacted By Opioid Misuse?

Discover what happens to your brain when you use opioids and the risk factors that can lead some people at greater risk for addiction or overdose death.

Opioids are powerful substances with the potential to be highly addictive because they activate natural reward systems in your brain. Even in a short amount of time, opioids can exert powerful effects on your brain’s function and structure.

Discover what happens to your brain when you use opioids and the risk factors that can lead some people at greater risk for opioid use disorder or overdose death.

What Happens to Your Brain When You Misuse Opioids?

Imagine you’ve just gotten home from a minor surgical procedure with a prescription for opioid painkillers. Following your doctor’s instructions, you take a pill for pain relief.

Inside your brain, the opioid drug switches off a group of nerve cells known as GABAergic neurons. This cluster of nerve cells helps to prevent dopamine from flooding the brain’s pleasure circuits; GABAergic neurons restrain the pleasure and euphoria networks.

GABAergic neurons are the gatekeepers preventing euphoria, pleasure, and dopamine from rushing your system, and opioid drugs disable GABAergic neurons from doing their job.

The result: opioid drugs release dopamine to flood your system with happy feelings while simultaneously banishing stress and anxiety.

The prefrontal cortex region of your brain is responsible for decision-making. And when it starts to associate opioid drugs or pills with that rush of dopamine, your brain begins to seek out more: more dopamine, more happiness, more opioids.

The signals from your brain say, “Taking this pill or doing this drug feels amazing! Let’s do it again.”

Unfortunately, regular opioid use leads to adaptation in the brain.

The neurons and nerve cells in your brain adjust, working even harder to fire off chemical messengers and return to stasis. Those neurons fire even more extensively. When opioids wear off and stop blocking certain signals, you experience the opposite of opioid effects.

Instead of euphoria and happiness, you experience anxiety and depression.

Instead of physical effects such as constipation and slowed respiration, you experience diarrhea, elevated blood pressure, and a racing heart.

And the prefrontal decision-making part of the brain says: “Whoah, we do not want to feel like this. Let’s avoid the catalyst that is making us feel bad, and in this case, what’s making us feel bad is not doing opioids.”

To make matters worse, opioid users also have to worry about tolerance.

Over time, the effect of opioids becomes less intense. It takes increasingly higher doses to feel the same effects. It’s common for clinical pain management patients to require a 10x increase in opioid dosage as they build up a tolerance to opioid painkillers.

Between the increasing tolerance, the need for higher and higher doses to get the same effect, and the brain sending signals that opioids are “good” (and that opioid withdrawal is very, very bad)—it’s no wonder that opioid use can quickly become misuse, dependence, and substance use disorder.

How Does Long-Term Opioid Use Change the Brain?

Use opioid drugs for too long, and the drugs will change your brain.

Research suggests that long-term opioid use or opioid dependence is associated with structural and functional changes in the brain. Opioid use notably impacts the brain regions involved in the regulation of affect and impulse control, as well as in the areas of the brain associated with rewards, motivation, and addictive behavior.

Long-term opioid use can actually damage the brain.

Brain injury professionals from the Academy of Certified Brain Injury Specialists (ACBIS) have reported an unprecedented uptick in the number of patients who have suffered a brain injury due to substance abuse, particularly opioid dependence.

Imaging scans have documented physical volume loss in the brain, in addition to cognitive and functional changes after long-term opioid use, resulting in long-lasting cognitive impairments.

Repeated exposure to escalating dosages of opioids alters the brain so that it functions more or less normally when the drugs are present and abnormally when they are not.

Why Are Some People More Likely to be Addicted to Opioids?

Two people are prescribed an opioid painkiller for postoperative pain following a minor surgical procedure.

One person uses the opioids as directed for the duration recommended by their doctor. They stop using opioids with no problem, dispose of any unused drugs, and don’t think about the painkillers again.

The other person misuses the opioid painkillers: increasing their dosage and decreasing the recommended time between doses. When their prescription bottle is empty, they ask their doctor for a refill.

And when their doctor refuses a second refill, this person finds themselves stealing pills from friends' homes and seeking illicit pills from any source. Purchasing heroin is easier and less expensive than seeking pills, and an overwhelming desire to avoid withdrawal symptoms makes heroin an easy choice to make.

What could be a short-term pain solution for one person can be the catalyst for misuse, abuse, and addiction for another.

Why are some people more likely to become addicted to opioids than others?

Prescribing Risk Factors

Some risk factors can increase an individual’s likelihood of opioid misuse or abuse, including:

  • High Dose: The higher the opioid dose, the higher the risk of misuse and overdose death. Larger doses (100 morphine milligram equivalents or higher) have over two times the risk relative to lower doses. Even low doses (such as 20-50 MME) can present a risk.
  • Prolonged Duration: Prolonged use is associated with a significant risk of addiction. Physical dependence and addiction to opioids may occur in as little as a few days. As many as one in four people receiving prescription opioids long-term in a primary care setting struggle with opioid addiction.
  • Extended-Release and Long-Acting Formulations: There are greater risks of overdose and death associated with extended-release and long-acting opioid formulations versus immediate-release formulations.

Individual Risk Factors

Some individuals with certain healthcare conditions or characteristics are at higher risk of misuse, which may lead to overdose.

These include:

  • Younger adults (18-25 years old)
  • Pre-existing mental health disorders (depression, anxiety, post-traumatic stress disorder)
  • History of alcohol or substance abuse

Genetic and Environmental Risk Factors

Research has shown links between genetic and environmental risk factors and opioid misuse, abuse, or addiction.

Opioids and other drugs of abuse act on the brain’s award system. Researchers have found that the function of this system can be affected by genetic factors, identifying a gene that regulates dopamine activity. This gene was frequently found in people with substance abuse disorders.

Additional evidence suggests that environmental factors such as stress can induce epigenetic gene changes that may trigger the development of psychiatric disorders and drug addiction. (Epigenetics refers to gene expression that can be switched on or off based on environmental factors.)

According to Harvard Medical School, a stressful situation such as the loss of a job or the death of a significant other can trigger the release of hormones that lead to epigenetic changes that can impact the brain’s reward system, leading to the development of addiction or inducing a relapse in drug or alcohol recovery.

Many factors determine if an individual will take them long enough to become dependent or addicted. Some of these factors are personal, while others have to do with the prescription or other factors such as one’s environment or genetics.

One of the biggest reasons opioid use becomes opioid misuse is the opioids' ability to provide intense feelings of pleasure—particularly in the early stages of use. Opioids stimulate the brain’s reward systems, compelling some people to take them repeatedly or more often than prescribed.

The compulsion to continue using opioids builds over time to extend beyond a simple drive for pleasure; as opioid use continues, the brain also seeks to overcome tolerance to the drug’s effects and avoid the extremely unpleasant effects of withdrawal.

If you have been prescribed an opioid painkiller, be sure to talk to your doctor about your risk factors for abuse, and secure your opioid medications to keep them out of reach of any children, teens, or visitors in your home.


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