Opioid Withdrawal Symptoms and Timeline

Opioid withdrawal begins 8 to 24 hours after the last dose of a short-acting opioid, 12 to 48 hours after a long-acting one, and peaks in intensity at 36 to 72 hours.

Per the World Health Organization, the acute course runs 4 to 10 days for short-acting opioids and 10 to 20 days for long-acting ones. Untreated opioid withdrawal has killed people through dehydration and cardiac complications, so clinicians manage the syndrome medically.

Key Takeaways

• Short-acting opioids produce withdrawal within 8 to 24 hours; long-acting opioids produce withdrawal within 12 to 48 hours.
• The Clinical Opiate Withdrawal Scale rates 11 signs and symptoms on a 0 to 47 total, and a score below 5 indicates no withdrawal.
• Untreated opioid withdrawal produces dehydration, hypernatremia and heart failure, and clinicians have documented deaths from all three.
• Overdose risk peaks in the first 1 to 2 weeks after cessation, reaching 12.7 times the state-resident death rate in the fortnight after prison release.
• Extended-release naltrexone requires a minimum 7 to 10 opioid-free days before the first dose.

What Should You Do in an Opioid Emergency?

A suspected opioid overdose requires 911 and naloxone given as quickly as possible, even when opioid involvement is uncertain. Per the FDA label, naloxone is safe to use even when opioids are not present, and CDC confirms naloxone does not harm a person who has taken no opioid.

Crisis resources. The 988 Suicide and Crisis Lifeline answers three ways: call 988, text 988, or chat at 988lifeline.org/chat. Spanish-language support answers by pressing 2, and the Lifeline’s videophone option serves ASL users. A medical emergency requires 911.

Heavy sedation on opioids is a medical emergency rather than sleep. Per SAMHSA, signs of overmedication that may progress to overdose include mental confusion, slurred speech, intoxicated behavior, slow or shallow breathing, and a slow heartbeat with low blood pressure. Those signs are what people describe as nodding off on opioids.

Five steps follow, drawn from the FDA naloxone labeling and CDC guidance, and calling for help does not wait on naloxone:

1. Rouse the person. Shout, shake, or apply firm pressure to the sternum.
2. Call 911. CDC directs responders not to wait for emergency workers before giving naloxone.
3. Give naloxone, even when in doubt.
4. Repeat every 2 to 3 minutes without a response, and give rescue breathing where trained.
5. Stay with the person. Naloxone lasts 30 to 90 minutes while many opioids last longer, so the overdose can return.

Fentanyl-involved overdoses frequently require repeat naloxone doses. How long that risk window stays open depends on which opioid produced the dependence.

How Long Does Opioid Withdrawal Last?

Acute opioid withdrawal lasts 4 to 10 days for short-acting opioids and 10 to 20 days for long-acting opioids. The World Health Organization ties both figures to the drug’s half-life: short-acting opioids leave the body quickly, so withdrawal starts sooner and ends sooner.

Opioid type	Examples	Withdrawal begins	Symptoms peak	Acute phase ends
Short-acting	Heroin, oxycodone, hydrocodone, morphine	8 to 24 hours after last use	36 to 72 hours	Day 4 to 10
Long-acting	Methadone	12 to 48 hours after last use	Not established in the primary guidelines	Day 10 to 20
High-potency synthetic	Fentanyl and its analogues	No published fentanyl-specific timeline	Not established	Variable, frequently prolonged

StatPearls classes oxycodone with the short-acting opioids at 12 to 18 hours, against 24 to 48 hours for long-acting agonists such as methadone. Filing oxycodone alongside methadone pushes a clinician toward a buprenorphine dose given too early.

No primary guideline publishes a fentanyl-specific withdrawal timeline. The literature instead proposes a mechanism affecting treatment: fentanyl’s potency and lipophilicity complicate buprenorphine initiation, and redistribution of fentanyl accumulated in fat stores may prolong opioid receptor occupancy. Clinicians treating fentanyl addiction plan for a longer stabilization period on that basis, which makes the symptom sequence below less predictable than the table suggests.

What Are the Symptoms of Opioid Withdrawal at Each Stage?

Opioid withdrawal produces autonomic symptoms first, gastrointestinal and cardiovascular symptoms at the peak, and psychological symptoms last. Seven early signs, six peak signs and five protracted signs mark the three stages.

Early Symptoms, 8 to 24 Hours

Seven signs open the syndrome:

• Muscle aches and joint pain
• Restlessness and agitation
• Anxiety and irritability
• Lacrimation and rhinorrhea, meaning watering eyes and runny nose
• Diaphoresis, meaning sweating
• Yawning
• Insomnia

Peak Symptoms, 36 to 72 Hours

Six signs define the peak:

• Nausea, vomiting and diarrhea
• Abdominal cramping
• Mydriasis, meaning dilated pupils, with blurred vision
• Tachycardia and raised blood pressure
• Piloerection, meaning gooseflesh, with chills alternating with sweating
• Cravings

The peak window drives most returns to use. Symptoms reach maximum intensity, sleep deprivation has accumulated across two days, and a single dose removes every symptom within minutes. Vomiting and diarrhea severe enough to prevent fluid retention is the mechanism by which untreated withdrawal has caused deaths, and medication prevents that mechanism.

Protracted Symptoms, Week One Onward

Five signs persist past the acute phase:

• Low mood and reduced motivation
• Anhedonia, meaning an inability to feel pleasure from ordinary activities
• Disrupted sleep with vivid dreams
• Impaired concentration
• Cue-triggered cravings

Per NIDA, repeated opioid use reduces the number of neurotransmitters the reward circuit produces and the number of receptors able to receive signals. The opioid-specific recovery timeline runs months to years, and patients with opioid use disorder in protracted abstinence showed incomplete recovery of nucleus accumbens function. Protracted withdrawal is a clinical description and not a DSM-5-TR diagnosis; SAMHSA’s own term is protracted withdrawal. Clinicians quantify all of this with a single scale.

How Do Clinicians Measure Withdrawal Severity?

Clinicians score opioid withdrawal with the Clinical Opiate Withdrawal Scale, abbreviated COWS, which rates 11 signs and symptoms on a total running 0 to 47. Wesson and Ling developed the scale in 2003, and six of the 11 items are purely objective.

The 11 COWS items are resting pulse rate, sweating, restlessness, pupil size, bone or joint aches, runny nose or tearing, gastrointestinal upset, tremor, yawning, anxiety or irritability, and gooseflesh skin.

COWS bands run mild at 5 to 12, moderate at 13 to 24, moderately severe at 25 to 36, and severe above 36. A COWS total below 5 indicates no withdrawal, and that band governs clinical practice more than the others, because buprenorphine given in that band precipitates abrupt severe withdrawal.

Per SAMHSA TIP 63, a patient exhibits signs of opioid withdrawal before taking the first buprenorphine dose. Buprenorphine carries weaker opioid agonist effects and stronger receptor affinity than full agonists, so buprenorphine displaces full agonists from the receptor. TIP 63 reports the buprenorphine Risk Evaluation and Mitigation Strategy threshold rather than issuing its own: a COWS score of 12 or higher typically suffices for a first dose, with at least 12 hours since a short-acting opioid and at least 24 hours since methadone. A COWS score explains the clinical picture; it does not explain why unsupported attempts fail.

Why Is Stopping Opioids Alone So Difficult?

Three factors defeat an unsupported withdrawal attempt: symptoms peak when physical capacity is lowest, tolerance falls faster than people expect, and protracted symptoms outlast the support most people arrange.

Symptom severity peaks at the point of least capacity. Sleep deprivation and dehydration impair judgment by the second day, and that day coincides with maximum symptom intensity and immediate access to relief.

Opioid tolerance declines after cessation, and the highest-risk window spans the first one to two weeks. Binswanger and colleagues measured all-cause mortality in the two weeks after prison release at 12.7 times the state-resident rate, with a drug-overdose standardized mortality ratio of 129. Merrall’s meta-analysis found drug-related death 3 to 8 times higher in weeks 1 and 2 than in weeks 3 to 12. The World Health Organization directs that everyone who has withdrawn from opioids receive advice about increased overdose risk from reduced tolerance.

A dose that was previously routine produces fatal respiratory depression on return. Naloxone belongs on hand throughout that window. Protracted symptoms then continue after the physical symptoms resolve, and low mood and anhedonia persist into a period when most people have stopped receiving support. Medication for opioid use disorder is what closes that gap.

How Is Opioid Withdrawal Treated?

Medical treatment addresses opioid withdrawal on two fronts: supportive medication eases acute symptoms, and three FDA-approved medications stabilize the underlying opioid use disorder. The FDA and SAMHSA TIP 63 name methadone, buprenorphine and naltrexone.

• Buprenorphine is a partial agonist that relieves withdrawal and reduces cravings. Prescribers commonly dispense buprenorphine as a buprenorphine and naloxone combination, sold as Suboxone.
• Methadone is a long-acting full opioid agonist and a Schedule II controlled medication, dispensed for opioid use disorder through federally certified opioid treatment programs.
• Naltrexone blocks opioid effects. The extended-release label specifies a minimum of 7 to 10 opioid-free days before the first dose, to avoid precipitating withdrawal severe enough to require hospitalization. Patients transitioning from buprenorphine or methadone remain vulnerable for as long as two weeks.

Supportive medication targets specific symptoms. Clonidine and lofexidine are both alpha-2 adrenergic agonists that reduce central noradrenergic outflow. Lofexidine holds FDA approval, granted in May 2018 as Lucemyra, for mitigation of opioid withdrawal symptoms in adults for up to 14 days. Clonidine carries no such indication and prescribers use clonidine off-label.

The FDA lists lofexidine as mitigating feeling sick, stomach cramps, muscle spasms and twitching, feeling of coldness, heart pounding, muscular tension, aches and pains, yawning, runny eyes and insomnia. Anti-emetic and anti-diarrheal medication prevents the dehydration that creates the medical risk. Heroin and prescription opioids share the same mu-opioid receptor mechanism and symptom profile, and onset and duration differ by half-life. Supervision decides whether medication reaches the patient at all.

When Does Opioid Withdrawal Need Medical Supervision?

SAMHSA TIP 45 names hospitalization or some form of 24-hour medical care as the preferred setting for opioid withdrawal, alongside alcohol and sedative-hypnotic withdrawal. Seven circumstances make that setting necessary rather than preferable.

• Vomiting or diarrhea preventing fluid retention
• Existing cardiac, pulmonary, hepatic or renal conditions
• Pregnancy, where medication for opioid use disorder is the standard of care
• Concurrent alcohol or benzodiazepine use, both of which produce withdrawal seizures
• Previous withdrawal attempts ending in return to use
• Suicidal thinking
• Absence of anyone able to check on the person through the first 72 hours

Medically supervised detox provides that setting. One belief about opioid withdrawal survives despite the evidence against it.

Is Opioid Withdrawal Really Dangerous, or Just Uncomfortable?

Untreated opioid withdrawal has killed people, and clinicians have documented the mechanism. The comparison with alcohol holds on magnitude and fails as reassurance.

Common misconception	What the evidence shows
“Opioid withdrawal will not kill you, it just feels terrible.”	StatPearls opens its account of the condition by describing opioid withdrawal syndrome as a life-threatening condition. Darke, Larney and Farrell documented deaths from untreated withdrawal in Addiction in 2017, through persistent vomiting and diarrhea producing dehydration, hypernatremia and resultant heart failure, in custodial settings where nobody managed the syndrome.
“Getting through detox is the hard part.”	Binswanger and colleagues measured all-cause mortality in the two weeks after prison release at 12.7 times the state-resident rate, with a drug-overdose standardized mortality ratio of 129. The fortnight after withdrawal carries more risk than the withdrawal.

Alcohol and benzodiazepine withdrawal kill more often, and neither figure above turns opioid withdrawal into a syndrome to ride out unsupported.

Where Can You Get Opioid Withdrawal Treatment in Los Angeles?

New Spirit Recovery provides medically monitored detox for opioid use disorder at its Tarzana, Northridge and Encino locations, with 24-hour medical and nursing supervision. Clinicians monitor withdrawal through the peak window and manage symptoms with medication.

Detox connects into medication-assisted treatment rather than ending when symptoms stop, because the protracted phase outlasts the acute one. An admissions assessment establishes the medication plan before the first dose.

“The part families do not expect is how much of detox is watching rather than treating. Nursing staff are checking for changes in condition around the clock, because the picture at hour 12 tells you very little about the picture at hour 48.”

– Cynthia Prieto, LVN, Director of Nursing at New Spirit Recovery.

Frequently Asked Questions

How long does opioid withdrawal last?

Acute opioid withdrawal lasts 4 to 10 days for short-acting opioids and 10 to 20 days for long-acting ones. Symptoms begin 8 to 24 hours after a short-acting opioid and 12 to 48 hours after a long-acting one, and heroin withdrawal peaks at 36 to 72 hours.

What is the worst day of opioid withdrawal?

For short-acting opioids the peak falls at 36 to 72 hours after the last use, which is day 2 to 3. Gastrointestinal symptoms, cravings and sleeplessness all reach maximum intensity in that window.

Can opioid withdrawal kill you?

Yes, though far less often than alcohol or benzodiazepine withdrawal. Clinicians have documented deaths from untreated withdrawal through persistent vomiting and diarrhea causing dehydration, hypernatremia and heart failure, mostly in custodial settings. Overdose risk after cessation is the larger danger.

When is overdose risk highest after stopping opioids?

The first one to two weeks. In the two weeks after prison release, all-cause mortality ran 12.7 times the state-resident rate with a drug-overdose standardized mortality ratio of 129, and drug-related death runs 3 to 8 times higher in weeks 1 and 2 than in weeks 3 to 12.

Does Suboxone stop withdrawal symptoms?

Buprenorphine, the active opioid in Suboxone, relieves opioid withdrawal symptoms and reduces cravings. Induction starts once a patient reaches established withdrawal, which the buprenorphine Risk Evaluation and Mitigation Strategy puts at a COWS score of 12 or higher, because earlier dosing precipitates abrupt severe symptoms.

How long must you be opioid-free before naltrexone?

A minimum of 7 to 10 days per the extended-release naltrexone label, to avoid precipitating withdrawal severe enough to require hospitalization. Patients transitioning from buprenorphine or methadone remain vulnerable for as long as two weeks.

What is protracted withdrawal?

Protracted withdrawal covers the low mood, poor sleep, reduced concentration and cue-triggered cravings continuing after the acute phase ends. The literature describes months to years with partial recovery of reward-system function. Protracted withdrawal is not a DSM-5-TR diagnosis.

Is opioid withdrawal worse than alcohol withdrawal?

Opioid withdrawal produces more physical discomfort, and alcohol withdrawal produces more deaths. Alcohol withdrawal produces seizures and delirium tremens, and delirium tremens carries a mortality of up to 37 percent without appropriate treatment.

References

1. World Health Organization. Clinical Guidelines for Withdrawal Management and Treatment of Drug Dependence in Closed Settings.
2. Substance Abuse and Mental Health Services Administration. (2021). Medications for Opioid Use Disorder. Treatment Improvement Protocol (TIP) Series, No. 63. SAMHSA Publication No. PEP21-02-01-002.
3. Substance Abuse and Mental Health Services Administration. (2006). Detoxification and Substance Abuse Treatment. Treatment Improvement Protocol (TIP) Series, No. 45.
4. Shah, M., Huecker, M. R. Opioid Withdrawal. StatPearls. National Library of Medicine.
5. Darke, S., Larney, S., Farrell, M. (2017). Yes, people can die from opiate withdrawal. Addiction, 112(2), 199-200.
6. Binswanger, I. A., et al. (2007). Release from prison: a high risk of death for former inmates. New England Journal of Medicine, 356(2), 157-165.
7. Wesson, D. R., Ling, W. (2003). The Clinical Opiate Withdrawal Scale (COWS). Journal of Psychoactive Drugs, 35(2), 253-259.
8. US Food and Drug Administration. Lucemyra (lofexidine) prescribing information; and Vivitrol (naltrexone for extended-release injectable suspension) prescribing information.
9. National Institute on Drug Abuse. Drugs, Brains, and Behavior: The Science of Addiction; and Naloxone DrugFacts.