What Is Opioid Tolerance?

Chronic use of opioid drugs like oxycodone and heroin can build what’s known as opioid tolerance.

Opioid tolerance occurs when your body becomes intolerant or accustomed to a certain dosage of an opioid, which can weaken or nullify the drug’s effects.

The development of opioid tolerance can cause some people to increase their opioid use. Without clinical guidance, this can increase the risk of opioid use disorder and addiction.

Here you’ll find information on:

• types of opioid tolerance
• causes of opioid tolerance
• signs of opioid tolerance
• risks of opioid tolerance
• finding treatment options for opioid use disorder

What Are Common Types Of Opioid Tolerance?

You can become tolerant to the effects of all opioid agonists, because they affect the central nervous system (CNS), consisting of the brain and spinal cord.

Common types of opioid tolerance include:

• oxycodone tolerance
• heroin tolerance
• fentanyl tolerance
• tramadol tolerance
• morphine tolerance
• hydrocodone tolerance
• Suboxone tolerance
• methadone tolerance

Opioid Tolerance Vs. Dependence Vs. Drug Addiction

Tolerance is sometimes confused with physical dependence on a drug, as well as drug addiction. But there are important differences between the three.

Opioid Tolerance

According to the U.S. National Institute on Drug Abuse, tolerance is what happens when the body no longer responds to a drug the same way.

This typically develops with chronic use—or, regular use for at least several weeks—as the body becomes accustomed to the drug and the side effects of opioids.

If you’re taking a prescription opioid and build tolerance, a doctor may direct you to increase your dosage, with instructions on how to do so safely.

Opioid Dependence

Drug dependence is different from tolerance. Unlike tolerance, opioid dependence can cause the body to go through drug withdrawal if the use of a drug is reduced or stopped very suddenly.

Like tolerance, dependence takes time to develop. It can also become more severe and potentially dangerous if it develops as a result of opioid abuse.

Opioid Addiction

Opioid addiction, also known as opioid use disorder, is a disease that’s characterized by compulsive drug use.

This can have a physical component (dependence) as well as a psychological component that can make it hard to quit the drug.

What Causes Opioid Tolerance?

A tolerance to opioids can develop through several different mechanisms and may be influenced in part by certain behaviors and environmental factors.

But the primary cause of opioid tolerance is long-term opioid use. For instance, taking a prescription opioid analgesic daily for several weeks or more.

Mechanisms for developing tolerance include:

• pharmacokinetic factors (i.e. metabolic tolerance)
• pharmacodynamic factors (i.e. functional tolerance)
• behavioral factors
• environmental factors
• genetics

Chronic opioid use causes repeated stimulation. This repeated exposure can then alter how the body reacts to a drug over time, requiring higher doses of the drug to experience the desired effect.

Signs Of An Opioid Tolerance

Signs that you have built up a tolerance or desensitization to opioids are fairly straightforward.

The primary signs of opioid tolerance include:

• needing larger concentrations of an opioid to feel its effects (e.g. pain relief)
• experiencing reduced analgesic effects over time when taking the same dosage

Increasing your opioid use, by taking high doses or taking doses more often, can lead to the development of a high tolerance.

People who have not taken opioids before, or take them infrequently, will have a low tolerance for opioids, which can be dangerous if exposed to a high dose.

Tolerance Loss During Abstinence

One of the most clinically important and least understood facts about opioid tolerance is that it decreases rapidly during periods of abstinence, even brief ones.

When a person abstains from opioid use, the body quickly loses tolerance to the drug, even within days to weeks after last use. This creates a dangerous window: if someone returns to their previous dose after a period of abstinence, there is a serious risk of overdose because they have lost their tolerance to the respiratory suppressant effects of opioids.

This risk is especially high during transitions such as completing detox, being released from incarceration, or being discharged from the hospital. These are moments when tolerance has been reduced but the underlying cravings and triggers often remain.

Crossover Tolerance With Opioids

The opioid drug class contains a wide range of opioid drugs, from the natural opiate morphine to fully synthetic opioids like methadone and fentanyl.

Because all opioids act on the same opioid receptors, the development of a tolerance to one will result in some level of tolerance for other opioids as well.

This is what’s known as crossover tolerance.

Overdose Risk

People with a low tolerance for opioids, including opioid-naive children, are at high risk for an opioid overdose when or if they are exposed to opioids.

When you have a low tolerance, your body will not respond to opioids in the same way as someone who takes opioids regularly. So, it can become more easily overwhelmed.

Dangers of overdose include:

• respiratory depression (slowed or stopped breathing)
• brain damage
• liver or kidney damage
• coma
• death

This is particularly relevant today because fentanyl now contaminates a wide range of illicit drugs, including cocaine, methamphetamine, and counterfeit pills. A person with no opioid tolerance who unknowingly ingests fentanyl faces an extremely high overdose risk, even from a small amount.

Naloxone (Narcan) can reverse an opioid overdose and is available without a prescription at most major pharmacies. Anyone at risk of opioid exposure, or who knows someone who is, should have it on hand.

Treatment For Opioid Tolerance And Addiction

Having a high analgesic tolerance is not dangerous by itself. But it can be if it’s accompanied by struggles with opioid use disorder or addiction.

Getting help for opioid use disorder through a treatment program is highly recommended, particularly if you have a high tolerance.

Opioid use disorder can be life-threatening and may affect all areas of your life, from your relationships, to mental health, and overall quality of life.

Treatment for opioid use disorder may involve:

• opioid detoxification
• medication for opioid use disorder (e.g., methadone, buprenorphine)
• behavioral therapy
• group therapy
• pain management care
• relapse prevention
• aftercare planning

Getting Help For Opioid Use Disorder And Addiction

Browse our directory or reach out to the Substance Abuse and Mental Health Services Administration (SAMHSA) for more information about addiction recovery.

Written by the Addiction Resource Editorial Staff