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Opioid Withdrawal Differs by Opioid TypeHow OWS Differs Between Short-Acting Opioids, Long-Acting Opioids, and MAT Medications 

A guest blog provided by Mark Pirner, M.D., Ph.D., US WorldMeds

Opioid Withdrawal Perpetuates Opioid Use

We’ve previously talked about how opioid withdrawal can be a major driver of continued opioid use and dependence. Even if people initially use opioids to get high, that changes over time. The brain builds tolerance, which then requires higher opioid doses to get the same effect, and eventually, the brain adaptations make abruptly discontinuing opioids extremely unpleasant. This is because the normal brain chemistry has changed to accommodate external opioid use, and when the external opioids are no longer available, the opioid deficit or gap results in extreme agitation, physical illness, depression, and fatigue. Eventually, and especially for people who have experienced withdrawal previously, keeping opioids on board becomes a necessity just to avoid getting sick.

Opioid Withdrawal Differs by Opioid Type

In general, there are some major differences between short-acting opioids (oxycodone, hydrocodone, hydromorphone, heroin) and longer-acting opioids (buprenorphine, methadone). Short-acting opioids (even the extended-release kinds) are broken down or leave the body after around 12 hours. Extended-release formulations stay in the gut longer (slow-release), so it takes longer for them to be fully absorbed, but once in the bloodstream the elimination is the same. In other words, the elimination is the same but the ‘clock starts ticking’ about 6-12 hours later for extended-release. The main result is that the severe physical opioid withdrawal symptoms typically start 6-12 hours after the last dose of immediate-release and 12-24 hours after extended-release opioids. Once started, the physical symptoms typically last 5-7 days and are worst around days 2-4.

Buprenorphine and methadone are different. Buprenorphine is eliminated from the bloodstream in about the same time frame as short-acting opioids, but the buprenorphine molecules bind much more tightly to the opioid receptors in the brain, and take longer to come off than, for example, heroin. This means that even if buprenorphine isn’t in the blood it can still be ‘stuck’ on the brain opioid receptors. As a result, opioid withdrawal from abrupt buprenorphine discontinuation usually starts around 24-36 hours and can last up to 2 weeks.

Methadone is stored in body fat, and as a result, it takes longer to ‘leach’ out of the fat in the body. This is why it takes longer to achieve a stable methadone dose (need to fill-up the fat stores before the blood levels become stable), and similarly why it takes longer to eliminate methadone from the body. Because of this, methadone withdrawal starts later and takes longer to complete, with timing like buprenorphine.

Why Do These Differences Matter?

Simply put, withdrawal from short-acting opioids is sooner, shorter, and more intense, whereas withdrawal from buprenorphine and methadone is later, less intense, and takes much longer to complete. People who have experienced withdrawal from both short-acting opioids (like heroin) and buprenorphine or methadone can describe these differences.

“Better or worse” depends on the individual, but it is important to understand what to expect.

Importantly, detoxification, whether from short- or longer-acting opioids, will end, so that “next” can begin.

About the author: Mark Pirner, M.D., Ph.D. is a senior medical director at US WorldMeds (, where he leads their medical affairs opioid withdrawal treatment portfolio. Dr. Pirner attended medical school at the University of Minnesota and, completed internal medicine residency at Duke University Medical Center and endocrinology fellowship at the National Institutes of Health. US WorldMeds is a wholly owned specialty pharmaceutical company based in Louisville, Kentucky, committed to raising awareness of opioid withdrawal syndrome and its treatment.