Opioid Tolerance: How the Body Builds Resistance

Medically Reviewed

Tolerance is an issue with many medications that are taken over significant periods of time. It’s often a sign of a growing substance use disorder. In many cases, you may be able to notify your doctor that you’re building a tolerance to medication and work with them to taper off or switch to a new medication. If you ignore a growing tolerance or if you adapt to it by increasing your dose, it could result in chemical dependency or addiction. How does tolerance work, and why is it a problem?

How Opioid Tolerance Works

Tolerance occurs when your body starts to adapt to a chemical substance. Tolerance often builds the longer you take a drug consistently, but it can also wear off when you cut back or stop using a drug. Opioid prescriptions can be potent, changing your brain chemistry over time. Short term opioid use is less likely to cause tolerance or dependence when you use the drug as directed. However, long-term use of opioid prescriptions is common, especially among people with chronic pain or long-lasting problems.

Long-term, regular use can cause your brain to adapt to the presence of an opioid in it. Your brain chemistry may change to balance the foreign chemical. You may stop producing the natural endorphins, which are your body’s opioid that’s released to manage pain.

Opioids work by binding to opioid receptors that are designed to be activated by endorphins in the body. Prescription and illicit opioids are often much stronger than your endorphins, leading to powerful effects that make them useful in treating moderate to severe pain. Opioids like morphine that are used to treat pain are called opioid receptor agonists, which means they bind to opioid receptors and activate them.

Why is Tolerance a Concern?

Tolerance can pose a problem to doctors and patients that are trying to deal with chronic pain. Chronic pain may warrant the long-term use of an opioid, which can increase a person’s risk of experiencing tolerance or dependence. According to an article published in The Journal of American Anesthesiologists, the opioid signaling system has the ability to develop a tolerance to a greater degree than other systems. This can lead to the need for higher and higher doses of the drug to achieve the same pain relief. Tolerance can also lead to what’s called opioid-induced hyperalgesia, which is an escalation of pain with higher doses of opioids. So, not only do opioids become more effective, but you experience more and more pain without them.

There is also the problem of what doctors call differential tolerance. Typically, when you develop a tolerance to a drug’s positive effects, you develop a tolerance to a drug’s negative effects as well. However, differential tolerance refers to the development of tolerance to different effects at different rates. Opioids are powerful pain-relievers, but they can also cause respiratory depression, which can slow your breathing down to dangerous levels. You may build a tolerance to an opioid’s pain-relieving ability faster than you can become tolerant to its ability to slow down your breathing.

When you’re taking an opioid, it’s important to communicate with your doctor regularly. Tell them about any new or changing symptoms and pay attention to the drug’s effect on you.

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