The Serious Side Effects of Long-Term Opioid Use

An American dies from an opioid overdose every 5 minutes in the U.S. Discover the serious side effects of long-term opioid use.

More than 20% of Americans suffer from chronic pain conditions, and many of them are turning to opioid painkillers as a solution. While the rate at which opioids are prescribed has declined over the past ten years to 43.3 opioid prescriptions dispensed per 100 persons in 2020, these rates remain high in some parts of the United States. In 5% of U.S. counties, there were enough opioid prescriptions dispensed for every person to have one.

While opioid prescriptions may have decreased in the past 10 years, opioid overdose deaths have not. 2021 reports show that opioid overdose deaths have hit an all-time high, with one opioid overdose death occurring in the United States every five minutes.

Opioids use is not without consequences. These powerful drugs can have a long list of side effects and long-term effects. Here’s what you need to know about how opioids work in your brain, body, and the side effects of short and long-term use.

What Are Opioids?

Opioids are a class of drugs also called narcotic painkillers and are derived naturally or synthetically from the opium poppy.

Some commonly used opioids include:

  • Fentanyl
  • Hydrocodone
  • Methadone
  • Morphine
  • Oxycodone

These painkillers have been used in brand-name “combination” drugs in which opioids are mixed with an over-the-counter pain reliever like acetaminophen or ibuprofen. Examples of such drugs include OxyContin and Percocet, which contains oxycodone, and Vicodin, which contains hydrocodone.

What Are Opioids Prescribed For?

Narcotic painkillers have been used to treat chronic pain and more common pain caused by back injuries, headaches, arthritis, and other conditions.

How Do Opioids Work?

Opioids don’t work by removing pain, but rather by decreasing the perception of pain and producing a sense of pleasure and well-being.

Opioid chemicals travel through the bloodstream to the brain, where they attach to specialized proteins on the surface of opiate-sensitive brain cells (neurons). This triggers a release of dopamine, a feel-good chemical that’s activated as a part of the brain’s reward system.

A woman looking at her phone.

What Are The Side Effects Of Opioid Use?

The most common side effects of opioid use are constipation and nausea. Other common side effects of opioid use include sedation, dizziness, vomiting, tolerance, physical dependence, and respiratory depression.

Less common side effects of opioid use may include:

  • Gastroparesis: a disorder also known as delayed gastric emptying, which slows or stops the movement of food from the stomach to the small intestine, leading to pain, excess gas, bloating, heartburn, and weight loss.
  • Hyperalgesia: hypersensitivity to pain caused by opioid use, which causes the nervous system to become overly sensitive to painful and non-painful stimuli.
  • Muscle rigidity: the inability of muscles to relax normally, causing muscle pain as muscles stay contracted for a long period of time.
  • Myoclonus: sudden involuntary jerking or twitching of a muscle or group of muscles which cannot be controlled.

Long-term use of opioid prescription medications (6 months of use or longer) can cause serious side effects, particularly when taken at high doses.

What are some of the more dangerous side effects?

What’s The Danger Of Long Term Opioid Use?

Prolonged use of opioids may have adverse consequences. Some of the less common side effects of opioid use mentioned above, such as hyperalgesia (increased sensitivity to pain), become more common when opioids are used in high amounts or over a longer period of time. Other long-term side effects of opioid use can include:

Hormonal dysfunction

Prolonged opioid use can have hormonal effects that result in changes in menstrual period and reduced fertility, libido, and sex drive.


Prolonged use of opioids can also result in immunosuppression: the weakening of the immune system. The most prevalent effect of opioid-induced immunosuppression has been reported as increased susceptibility to infection, increased risk of cancer, and an increased risk of HIV infection in drug abusers.

Long-term opioid use can lead to:

  • Abnormal pain sensitivity
  • Amenorrhea or irregular menses
  • Increased risk of AFib, heart attack, and heart infection
  • Galactorrhea, excessive or inappropriate production of milk
  • Immunosuppression
  • Increased risk of overdose
  • Reduced energy and drive
  • Reduced fertility
  • Reduced libido
  • Testosterone depletion

Distressed woman with her arms wrapped around her torso.

Opioid Addiction: A Serious Side Effect Of Long-Term Opioid Use

The physical side effects of opioid use can range from uncomfortable to life-threatening. But the potential for abuse deserves extra attention. Because the risk of developing an addiction to opioids is high, and one of the major reasons that America is in the midst of an unprecedented opioid crisis.

Multiple factors can lead to opioid addiction.

Your Brain on Opioids: Pursuing the Reward

Remember how opioids work: they reduce pain perception by triggering pleasurable chemicals to be released and activating the brain’s reward system.

The brain associates the action of taking the opioid with a pleasurable reward event. The brain is wired to continue seeking pleasurable actions/ events, which can lead to a subconscious “craving” for more and more opioid use. In other words, the brain is learning that opioid use is a positive experience that should be repeated.

Opioid Tolerance: The Need for More

One of the most common side effects of opioid use, especially long-term use, is tolerance. Opioid tolerance occurs when an individual needs greater amounts of a drug to achieve its therapeutic effect.

When someone first receives an opioid prescription, for example, they may need two pills per day to reduce their perception of pain. However, as time goes by, it begins to take three, four, or more pills per day to achieve the same pain-relieving effects.

At some point, their medical professional may prescribe a more potent, longer-acting opioid. But over time, the patient can become tolerant to even the most potent prescription, requiring more and more of the drug to get the same effect.

Opioid Withdrawal

Another factor contributing to a high risk of opioid abuse is physiological withdrawal symptoms. The prolonged use of opioids changes the way nerve receptors work in the brain, eventually becoming dependent on the drug to function. When an opioid user stops or decreases opioid use, it can lead to physical symptoms of withdrawal, which can range from mild to moderate or severe.

Opioid withdrawal symptoms may include:

  • Muscle aches
  • Restlessness
  • Anxiety
  • Eyes that tear up
  • Runny nose
  • Excessive sweating
  • Inability to sleep
  • Yawning very often
  • Diarrhea
  • Abdominal cramping
  • Goosebumps on the skin
  • Nausea and vomiting
  • Dilated pupils and possibly blurry vision
  • Rapid heartbeat
  • High blood pressure

Opioid withdrawal symptoms can be very uncomfortable, and opioid users may continue to take their drugs to avoid the physical withdrawal effects.

Fatal Overdose: The Lethal Side Effect Of Opioid Use

One final effect of opioid use must be addressed: the risk of fatal overdose.

Opioids, primarily synthetic opioids, are the main driver of drug overdose deaths in the United States. As opioid prescriptions have increased, the rate of opioid overdose deaths has increased in parallel. Opioids are prescribed three times as often in 2019 as they were in 1999 – and the rate of opioid deaths has quadrupled.

As of 2021, an opioid overdose death occurs once every five minutes in the U.S.

Common drugs involved in prescription opioid overdose deaths are:

  • Methadone
  • Oxycodone (Oxycontin)
  • Hydrocodone (Vicodin)

But the largest risk for opioid overdose deaths comes from synthetic opioids, such as fentanyl.

Fentanyl is a synthetic opioid that is cheap to manufacture and 50x - 100x more powerful than morphine. Fentanyl is often cut into illicit street drugs, such as heroin and cocaine, or pressed into pill form and sold on the streets as counterfeit painkillers.

Those with substance abuse disorders who can no longer easily get prescription opioids from their medical providers often turn to the streets to purchase heroin and painkillers. The cost is cheap and access is easy.

Unfortunately, the result can be deadly.

The amount of fentanyl that can lead to an instant overdose death can be as small as a single grain of sand.

Not every person who uses opioids will become physically dependent, addicted, or will be the victim of a fatal overdose. However, opioid misuse, abuse, and addiction rates are estimated to range from 15% to 26%. That means one in every four opioid users is at risk of falling victim to the dangerous effects of opioid abuse, with potentially fatal results.

Bottle of Hydrocodone pills.

Is Opioid Use Right For You?

Chronic pain is one of the most prevalent medical conditions and one of the most difficult to manage. Key patient advocacy and health organizations that strongly support the use of opioids to treat chronic pain have published consensus statements to guide physicians in prescribing these drugs. However, a standardized approach has yet to be met.

If you are considering long-term use of opioids, be sure that:

  • Non-opioid therapy has failed.
  • You understand the true benefits and risks of the long-term use of opioids.
  • The initial dose of opioid medication increases should be achieved within weeks.
  • Opioid dosage is moderate.
  • Further increases in the dose are introduced with extreme caution.
  • You use a single physician and pharmacy.
  • You use adjunctive treatments for pain whenever possible.
  • Your doctor fully documents the entire prescription process, which should include an initial, comprehensive medical history and physical examination, agreed-on goals for treatment, regular assessment of whether the goals are being achieved, and careful monitoring for signs of opioid abuse (including toxicologic screening in some cases).
  • You are willing to end opioid treatment if the goals are not met.

In general, experts advise that in the treatment of chronic pain, opioids be used at low or moderate doses. To decrease the risk of negative or adverse side effects, it is suggested that you are monitored closely to make sure you are still benefiting from the drugs in terms of pain relief and physical function. If not, it might be time to consider other options.

This post is the first in our series about the serious side effects of opioid use. For more information, please see our second post: The Serious Cardiovascular Side Effects of Opioid Useto learn more about the risks opioids pose to heart health.

This article was originally written by Lee Weber, Editor of Addiction Blog. It has since been updated to reflect current statistics and data and to provide additional information on the side effects and long-term effects of opioid use.

Lee Weber is the main writer, editor, and voice behind Addiction Blog, an online journal that documents alcohol, drug, and prescription drug addiction and its treatment. She believes that safe and responsible prescription of opioid medications should be regulated to prevent haphazard physicians from profiting from pharmaceutical commissions.


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