Most buprenorphine docs know that long-acting agonists like methadone complicate induction. In fact, doctors who induce 24 hours after a patient stops methadone learn never to do it again – or to ensure the patient does it at home! I write ad nauseam about precipitated withdrawal on this blog, so feel free to use the search function. I have learned the hard way that fentanyl also complicates buprenorphine induction.

The high affinity of buprenorphine allows the drug to displace most opioid agonists. That displacement results in a resetting of tolerance to match the potency of buprenorphine, creating severe withdrawal symptoms (naloxone has nothing to do with precipitated withdrawal). Those symptoms are largely avoided after a period of abstinence that eliminates opioids from the body. The induction process is more difficult now that many patients, knowing or not, use fentanyl.

Opioid Withdrawal

Fentanyl is used routinely in operating rooms. The drug is integral to modern anesthesia because of its almost immediate onset and high potency without the histamine release associated with natural opiates. Despite the drug’s utility, it has gained a dirty name from an association with over 100,000 overdose deaths annually in the United States. Fentanyl is lipid soluble and crosses into the brain instantly, resulting in the cessation of respiration (apnea) until carbon dioxide levels are high enough to stimulate breathing. During that apnea, blood oxygen saturation falls, causing cardiac arrest.

Anesthesiologists appreciate fentanyl because for most cases, the effects are short-lived. After IV administration, the drug crosses the fatty blood-brain barrier instantly. The lipid solubility that creates a rapid onset also causes the opioid effect to wear off as the drug leaves the brain, re-enters circulation, and distributes in fatty tissues throughout the body.

In short cases, fentanyl redistributes from the brain to fat tissue with a half-life of only 1.7 minutes. But when used daily or in large doses, fentanyl accumulates in fat tissue with a terminal half-life of 4 – 10 hours. Fat tissues can accumulate very large amounts of fentanyl over time, and eliminating fentanyl from the body can take many days.

The last four patients I induced tested strongly for fentanyl and had no heroin or other opioids in their urine. All four patients had difficult inductions similar to those of patients taking methadone. I suggest that the difficulty of induction was caused by the accumulation of fentanyl and the long time needed to eliminate fentanyl from fat stores in the body.

The first of these four patients waited 24 hours before induction. He developed severe precipitated withdrawal. Unlike the precipitated withdrawal I have seen in heroin users that lasts about 24 hours, this withdrawal continued for several days. I trusted him to avoid all opioid agonists and gave him three doses of clonazepam and clonidine to help him get through withdrawal.

I was better prepared for the next three patients who tested positive for fentanyl and asked them to wait longer before induction. Each patient insisted that they abstained for longer than 72 hours, but all three had severe precipitated withdrawal lasting at least 3 days. I don’t yet know the time interval needed to avoid precipitated withdrawal, and determining that interval from person to person will be difficult given that patients themselves usually have no idea how long they’ve been using fentanyl.

Doctors new to the induction process would save themselves some headaches by testing new patients for fentanyl. I purchased individual fentanyl POC strips to test my next new patient daily, and I will hold off on induction until the test is negative. I haven’t done enough recent inductions to determine if a negative strip guarantees no precipitated withdrawal, but I suspect that a positive test suggests withdrawal is likely.

Over time we will hopefully learn the best way to induce in such settings. Have you noticed what I described? How did you get around it? Does micro-dosing buprenorphine help? Please consider sharing your experience as a patient or as a prescriber.

Finally, I hope to write more frequently going forward. Most readers know my medical situation last
year, and those who are interested can read about it at . Things are going well these days and I am grateful for the chance to stick around a bit longer. I received so many messages of support last year, and I know they played a big role in my recovery.

Sadly, I let go of the forum. It went down again a few months ago, likely from the combination of old software, being 15 years old, and constant spam attacks. There is much more out there about buprenorphine than there was in 2007, but sadly, nothing out there includes the raw honesty that people shared in the forum.

Cheers everyone!

Categories: Science


Anonymous · September 19, 2023 at 4:46 pm

Glad you are back!

    J Junig MD PhD · September 23, 2023 at 11:03 am

    Thank you!

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