Opioid withdrawal: what to expect and where the danger is

With short-acting opioids like heroin or morphine, withdrawal usually starts 8 to 12 hours after the last dose, peaks at 48 to 72 hours and clears in 7 to 10 days, according to ASAM’s 2020 opioid guideline. Methadone is slower: symptoms may not start for 1 to 3 days, peak between days 3 and 8, and can last several weeks.

Uncomplicated opioid withdrawal is rarely deadly on its own. The bigger danger comes after, when tolerance is gone. If someone can’t be woken or is barely breathing, give naloxone if you have it and call 911.

The timeline

	Short-acting (heroin, morphine)	Long-acting (methadone)
Symptoms start	8 to 12 hours after last dose	1 to 3 days after last dose
Peak	48 to 72 hours	Days 3 to 8
How long	Clears in 7 to 10 days	May persist several weeks

That’s ASAM’s version. SAMHSA’s TIP 63 gives slightly wider ranges: early withdrawal at 8 to 24 hours for short-acting opioids and up to 36 hours for long-acting ones, with total duration of 7 to 10 days versus 14 days or more.

What about fentanyl? We haven’t found a guideline or study that gives a separate fentanyl withdrawal timeline, so we don’t print one. What is documented about fentanyl concerns starting buprenorphine, in the section on precipitated withdrawal.

Symptoms

ASAM lists craving, anxiety, low mood, yawning, sweating, gooseflesh, watery eyes, runny nose, insomnia, nausea or vomiting, diarrhea, cramps, muscle aches and fever.

Clinicians often score this with the COWS (Clinical Opiate Withdrawal Scale), an 11-item checklist. Scores of 5 to 12 are mild, 13 to 24 moderate, 25 to 36 moderately severe, and above 36 severe. At the severe end, TIP 63 describes diarrhea and vomiting, dehydration, low blood pressure, high blood sugar and lying curled up.

When to call 911

• Someone can’t be woken up, or their breathing is very slow or has stopped. Give naloxone if you have it, then call.
• They’ve also taken benzodiazepines, alcohol or other sedatives and are very hard to rouse.
• Vomiting or diarrhea is so heavy they can’t keep fluids down and seem dried out, dizzy or faint.

The danger after withdrawal

Unlike alcohol and sedative withdrawal, uncomplicated opioid withdrawal is not life-threatening, per TIP 45. Complications can still happen, mostly from fluid loss, and should be treated quickly.

During withdrawal your body loses its tolerance. If you use again at the dose you used to take, that dose can now stop your breathing. TIP 63 lists using after a period of abstinence, including after medically supervised withdrawal, as an overdose risk. It also notes that most people with opioid use disorder who go through supervised withdrawal start using again and don’t stay in care.

Two studies show the pattern. In a London study (Strang, BMJ 2003), 3 of 137 people followed after inpatient detox died of overdose within 4 months of discharge. All 3 had completed detox and lost tolerance. It’s a small study, and the authors said it urgently needed replication.

In a study of 40,885 insured US adults with opioid use disorder (Wakeman, JAMA Network Open 2020), only treatment with buprenorphine or methadone was linked to lower overdose risk, at 3 months (adjusted hazard ratio 0.24) and 12 months (0.41). Inpatient detox or residential services alone were not.

ASAM warns that stopping abruptly can put someone at risk for relapse, overdose and overdose death. Ultra-rapid detox under anesthesia is not recommended because of the high risk of serious harm or death.

Medications that ease withdrawal

ASAM recommends methadone or buprenorphine for withdrawal management over abrupt stopping. Both work better than the alternatives at easing symptoms and keeping people in care through the end of withdrawal. By federal rule, methadone for withdrawal has to be given in an opioid treatment program (OTP) or, in limited cases, a hospital.

Alpha-2 agonists are the non-opioid option, and ASAM calls them safe and effective for opioid withdrawal. Lofexidine (Lucemyra) was approved by the FDA on May 16, 2018, to ease withdrawal symptoms in adults stopping opioids abruptly; the label allows use for up to 14 days. Clonidine is used off-label for the same purpose.

Naltrexone is different. It blocks opioids, so it can’t be started until you’ve been off short-acting opioids for at least 7 days, or off long-acting ones for 10 to 14 days (TIP 63).

Precipitated withdrawal and fentanyl

Precipitated withdrawal is withdrawal set off suddenly when the opioid already on your receptors gets displaced, as ASAM defines it. With buprenorphine, the risk comes from taking the first dose too soon. ASAM’s rule is that buprenorphine shouldn’t be started until there are objective signs of withdrawal. Under buprenorphine’s safety program, a COWS score of 12 or higher is typically the threshold a clinician uses before a first dose, TIP 63 notes.

Fentanyl seems to make this harder. A 2022 self-report survey of 1,679 people at 49 US treatment centers (Varshneya, Journal of Addiction Medicine) looked at people who started a medication less than 24 hours after fentanyl: 22.19% of those on buprenorphine reported severe withdrawal, against 11.56% of those on methadone. Starting buprenorphine 24 to 48 hours after fentanyl still carried higher odds of severe withdrawal (odds ratios 5.20 within 24 hours and 3.35 at 24 to 48 hours). Methadone didn’t show the same link. These are people’s own reports, not measured in a clinic, but they’re a reason to start buprenorphine with a clinician who knows you’ve used fentanyl.

Naloxone

Narcan 4 mg naloxone nasal spray became the first naloxone product approved for sale without a prescription on March 29, 2023. ASAM says naloxone should be given to anyone being treated for, or with a history of, opioid use disorder. Keep it where the people around you can find it, and tell them where it is.

Choosing a program

Ask for a program that offers buprenorphine or methadone, not just a few days of symptom relief. Search by ZIP in the finder. SAMHSA’s National Helpline, 1-800-662-4357 (free, 24/7), refers callers to local treatment. Then read what comes after detox, because the weeks right after withdrawal are when overdose risk is highest.

Sources

• ASAM, The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update, J Addict Med, released Mar 2020
• SAMHSA, TIP 63: Medications for Opioid Use Disorder, 2018 edition
• SAMHSA, Quick Guide for Clinicians Based on TIP 45: Detoxification and Substance Abuse Treatment, based on TIP 45 (2006)
• Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS), J Psychoactive Drugs, 2003
• FDA label, LUCEMYRA (lofexidine), label effective Jul 22, 2026; original approval May 16, 2018
• Strang J, et al. Loss of tolerance and overdose mortality after inpatient opiate detoxification, BMJ, May 3, 2003
• Wakeman SE, et al. Comparative Effectiveness of Different Treatment Pathways for Opioid Use Disorder, JAMA Netw Open, Feb 2020
• Varshneya NB, et al. Evidence of Buprenorphine-precipitated Withdrawal in Persons Who Use Fentanyl, J Addict Med, 2022 (epub Nov 23, 2021)
• FDA, FDA Approves First Over-the-Counter Naloxone Nasal Spray, Mar 29, 2023
• SAMHSA National Helpline, last updated Jun 9, 2023