Fentanyl is a powerful opioid that treats severe pain symptoms. But using it for too long can lead to tolerance and chemical dependence. Fentanyl is also used as a recreational substance, which can come with severe consequences, including deadly overdoses. Tolerance can make treatment with the medication less effective, and when your pain symptoms become too much, you may need to switch to other options. But is it possible to reverse fentanyl tolerance? How long does it take to return to a normal level of tolerance? Learn more about fentanyl and how it works in your brain and body.

What Is Fentanyl?

Fentanyl is an opioid similar to oxycontin, morphine, and heroin. However, it’s in a specific category called synthetic opioids, which are entirely created in laboratories. Opiates like morphine and codeine are found in nature. Semi-synthetic opioids are created from natural opiates, including hydromorphone and oxycodone. Semi-synthetic drugs like fentanyl and its analogs are often extremely potent.

As a powerful opioid, fentanyl can be used as a pain reliever for moderate-to-severe pain symptoms. It’s used in hospital and battlefield settings to offer fast-acting relief from intense pain. It may also be used to manage acute pain symptoms through a transdermal patch, which can be placed on the skin where it offers pain relief for hours.

However, fentanyl is used outside of medical settings as a recreational drug. The fentanyl that is increasingly available on the street doesn’t usually come from legitimate pharmaceutical sources like other misused prescription drugs. Instead, it’s made in illegal laboratories outside of the U.S. and then trafficked into the country over the border or by ship. The recreational use of fentanyl is extremely dangerous because the drug is so powerful. The average person can overdose on a dose as small as 2 mg (milligrams), which is difficult for drug dealers to accurately measure out in unprofessional settings.

Fentanyl has also been implicated in the spike in overdose deaths in the United States over the past several years. Synthetic opioids, like fentanyl and its analogs, were involved in 57,834 overdose deaths in 2020 and 71,238 in 2021. Overall, there were an estimated 107,622 overdose deaths in 2020, which means that more than 66% involved synthetic opioids.

How Fentanyl Affects the Brain

As an opioid, fentanyl primarily works in the brain by binding with opioid receptors. These receptors are intended to work with naturally occurring chemicals in your brain and body called endorphins. These chemical messengers bind to opioid receptors all over your body’s nervous system to manage your pain response. When opioid receptors are activated, they will block pain signals from being sent and received through the nervous system. This can relieve your pain symptoms, which allows you to rest and recover from strain and minor injuries. However, moderate and severe pain is too much for your endorphins to mask.

Opioids are extremely similar to endorphins to the point that they can bind to opioid receptors in your brain to activate the pain-blocking effects. However, opioids like fentanyl are much stronger and more effective than endorphins, allowing them to block even severe pain symptoms. Fentanyl is particularly strong among opioids, and it can be effective in tiny amounts. It can also work quickly, which makes it useful in treating severe, acute pain.

Fentanyl, like other opioids, can also have other effects on the brain besides pain relief. Opioids can also affect dopamine levels in the brain. Dopamine is another natural neurotransmitter that’s tied to reward and motivation. It’s also involved in the development of substance use disorders and addiction. Dopamine is an essential part of your brain’s reward system. It’s intended to encourage you to repeat healthy tasks.

However, the powerful dopamine response caused by fentanyl can reinforce drug use. Because your brain will start to associate fentanyl with a powerful dopamine release, you will begin to crave it more and more. Ultimately, addiction is characterized by uncontrolled compulsions to use a drug, even despite the consequences.

Fentanyl Tolerance Development

Tolerance is when the effects of a drug decrease over a period of consistent use. It may be difficult to imagine that anyone could build a tolerance to a drug as potent as fentanyl, but the human brain is extremely adaptable. Tolerance is a product of your brain’s ability to adapt and adjust to the consistent presence of a drug.

If you’ve been taking opioids for a long time, your brain and body will alter brain chemistry balance around the foreign chemical. You may develop fentanyl tolerance when your body decreases the number of opioid receptors or increases the number of pain receptors through your nervous system. With more pain receptors, pain signals will continue despite the use of an opioid, especially if there are fewer opioid receptors.

As opioid tolerance increases, the severity of your opioid dependence may also increase. Dependence can cause uncomfortable withdrawal symptoms, and it could develop into an opioid use disorder.

What Are Fentanyl Tolerance’s Effects?

Tolerance is a major problem when it comes to treating the problem the medications were being used to address. Opioids like fentanyl are among the most potent pain relievers available. Because they are powerful and come with a risk of dependence, they are usually used when other options wouldn’t work. If you become tolerant to an opioid, there may not be other pain relief options to switch to. Fentanyl is often used to treat people who are tolerant of other opioids.

For instance, Duragesic is a brand name for a transdermal fentanyl patch that delivers a high concentration of fentanyl, which is only safe in people who are opioid-tolerant. But if your tolerance continues to grow as you take fentanyl, you may need higher and higher doses to achieve the same effects.

Dependence and Withdrawal Risk

Increasing your dose of an opioid as you develop a higher and higher tolerance increases your right of chemical dependence and a substance use disorder. Tolerance is a clear sign of a growing dependence on the drug. As your body adjusts its chemistry to include the opioid, the more it will rely on it. If you stop taking the opioid, you will experience uncomfortable withdrawal symptoms. If you’ve become tolerant to a significant dose of a potent opioid like fentanyl, your withdrawal symptoms may be even more severe.

Opioid withdrawal symptoms usually aren’t life-threatening, but they can cause uncomfortable symptoms and medical complications. Withdrawal from opioids is often compared to the flu, with symptoms like:

  • Runny nose
  • Teary eyes
  • Nausea
  • Vomiting
  • Diarrhea
  • Fever
  • Sweating
  • Body aches
  • Fatigue
  • Opioid cravings

Opioid withdrawal symptoms cause similar complications to the flu, including dehydration. If you can’t keep fluids down, you should seek medical attention immediately. However, the uncomfortable symptoms and powerful drug cravings are likely to cause a relapse or continued drug use. In many cases, detox and rehab are necessary to achieve lasting sobriety.

Overdose Risk

Fentanyl tolerance may also increase your risk of overdose. An opioid overdose can be deadly, causing symptoms like respiratory depression, loss of consciousness, and changes in blood pressure. Without medical intervention, opioid overdoses can lead to oxygen deprivation and death. Overdoses occur when you take a high dose, but they can also occur after a period of abstinence. People who develop a tolerance to opioids over time can lose their tolerance after a period of abstinence. If you relapse or return to opioid use and take the high dose you were used to, it can lead to an overdose.

Do Fentanyl Patches Cause Tolerance?

Fentanyl can be administered via transdermal patches, which is a unique method of administration for an opioid. Patches slowly deliver the medication over time, providing hours of pain relief. It’s relatively safe to use in this way unless the patch is broken or compromised in some way. However, like other means of administration, you can become opioid-tolerant with the use of patches. It’s likely to occur in people who use the patches long-term.

Can You Reverse Fentanyl Tolerance?

Tolerance is a difficult medical complication to deal with, but it can be reversed with abstinence from fentanyl. However, abstinence may present its own challenges. A tolerance break can help your body return to normal after a period of consistent drug use. Your doctor may recommend taking tolerance breaks as a part of your therapeutic use of the drug. A tolerance break may involve switching to another drug that works differently.

However, all opioids are fairly similar, and fentanyl is among the most potent. Switching to another pain reliever may offer some relief, but it won’t stop the pain as effectively. Still, there are other pain management options like physical therapy, anti-inflammatory drugs, antidepressants with pain relief qualities, and behavioral therapy.

If you’ve become chemically dependent on a drug, you may need to undergo a tapering schedule or a detox program. Once you stop using an opioid, your tolerance will begin to reverse after a few days, and it may return to normal after a few weeks.

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