We are independent & ad-supported. We may earn a commission for purchases made through our links.
Advertiser Disclosure
Our website is an independent, advertising-supported platform. We provide our content free of charge to our readers, and to keep it that way, we rely on revenue generated through advertisements and affiliate partnerships. This means that when you click on certain links on our site and make a purchase, we may earn a commission. Learn more.
How We Make Money
We sustain our operations through affiliate commissions and advertising. If you click on an affiliate link and make a purchase, we may receive a commission from the merchant at no additional cost to you. We also display advertisements on our website, which help generate revenue to support our work and keep our content free for readers. Our editorial team operates independently of our advertising and affiliate partnerships to ensure that our content remains unbiased and focused on providing you with the best information and recommendations based on thorough research and honest evaluations. To remain transparent, we’ve provided a list of our current affiliate partners here.

What Is Opioid Tolerance?

By Christina Hall
Updated Feb 12, 2024
Our promise to you
WiseGeek is dedicated to creating trustworthy, high-quality content that always prioritizes transparency, integrity, and inclusivity above all else. Our ensure that our content creation and review process includes rigorous fact-checking, evidence-based, and continual updates to ensure accuracy and reliability.

Our Promise to you

Founded in 2002, our company has been a trusted resource for readers seeking informative and engaging content. Our dedication to quality remains unwavering—and will never change. We follow a strict editorial policy, ensuring that our content is authored by highly qualified professionals and edited by subject matter experts. This guarantees that everything we publish is objective, accurate, and trustworthy.

Over the years, we've refined our approach to cover a wide range of topics, providing readers with reliable and practical advice to enhance their knowledge and skills. That's why millions of readers turn to us each year. Join us in celebrating the joy of learning, guided by standards you can trust.

Editorial Standards

At WiseGeek, we are committed to creating content that you can trust. Our editorial process is designed to ensure that every piece of content we publish is accurate, reliable, and informative.

Our team of experienced writers and editors follows a strict set of guidelines to ensure the highest quality content. We conduct thorough research, fact-check all information, and rely on credible sources to back up our claims. Our content is reviewed by subject-matter experts to ensure accuracy and clarity.

We believe in transparency and maintain editorial independence from our advertisers. Our team does not receive direct compensation from advertisers, allowing us to create unbiased content that prioritizes your interests.

Opioid tolerance is a process of neuroadaptation that results in opioid medications becoming less effective as analgesics at a set dose. The phenomenon of desensitization occurs at varied times for different patients and is also more pronounced, affecting things like mood and concentration, in patients who are susceptible or have comorbid mental illness with their pain. Degrees of opioid tolerance are commonly seen in patients who have been taking opioid medications for more than a few weeks. The worst desensitization and tolerance are seen in patients who have been on high doses of opioids for an extended period of time, not uncommonly multiple years. In these cases, the neuroadaptation, mainly opioid receptor downregulation, is usually the most severe and often times requires an extended period of medication tapering to avoid painful opioid withdrawal symptoms.

Patients may exhibit an unexpected insensitivity to an opioid medication upon its initial dose, called innate opioid tolerance. Innate tolerance is usually genetically linked and the use of a different medication that works in a slightly different way usually proves successful for pain management. Pharmodynamic tolerance, seen when neuroadaptation is present, is responsible for most cases of opioid tolerance and the associated complications of breakthrough pain, rise in the experience of side effects, and the need to increase opiate dosage to an unsafe threshold. Neuroadaptation in pharmodynamic tolerance is seen when peptides, opioid receptors, and signaling mechanisms change in response to chronic exposure to opiate medication. The most common adaptation is downregulation of opiate-specific receptor sites, causing a lowered density of active sites available to attach and metabolize opioid medications.

Opioid dependence, or the inability to decrease dosage without painful symptoms, is associated closely with opioid tolerance. When an opiate is abruptly discontinued, acute withdrawal symptoms like severe dysphoria and vomiting are common. The degree to which a patient experiences withdrawal symptoms has been shown to correlate with the amount and type of opioid medication being ingested. For example, methadone, an opiate drug that is used to mitigate withdrawal symptoms, is more effective than other medications in this capacity because it has a significantly long half-life. Drugs with a shorter half-life, like hydrocodone, for example, can lead more quickly to opioid dependence and discontinuation withdrawal symptoms develop in less time.

The mechanism of opioid tolerance is not completely understood, which is due, in part, to the many subtypes of opiate receptors. The most commonly affected receptors include the mu, delta, and kappa, which can be further classified into multiple subtypes, adding to the inherent complexity surrounding the issues of opioid tolerance and dependence. Each opioid medication works by attaching to a unique combination of receptors, leading some clinicians to treat tolerance issues by switching medications frequently.

WiseGeek is dedicated to providing accurate and trustworthy information. We carefully select reputable sources and employ a rigorous fact-checking process to maintain the highest standards. To learn more about our commitment to accuracy, read our editorial process.
Discussion Comments
By anon304536 — On Nov 20, 2012

What should a person do if they abused opiates for a long period of time at very high and consistent dosages (several hundred mgs of oxy a day), and they quit opiates but just over two weeks later get very sick and actually are in a lot of pain. Then they go to the hospital and the small amounts of morphine the docs give them don't even make their pupils small and the pain is unbearable and they don't have any money?

WiseGeek, in your inbox

Our latest articles, guides, and more, delivered daily.

WiseGeek, in your inbox

Our latest articles, guides, and more, delivered daily.