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KEY TAKEAWAYS

Fentanyl detox is done by:

Administering Buprenorphine after 12 – 24 hours of last using fentanyl for up to 14 days to alleviate physical and psychological withdrawal symptoms [1]
Conducting daily assessments using The Clinical Opiate Withdrawal Scale (COWS) and providing symptomatic treatment as needed (e.g. Loperamide, Aspirin)

How Is Fentanyl Detox Done?

Buprenorphine is used during fentanyl detoxification to manage withdrawal symptoms and drug cravings in patients with a fentanyl addiction by:

Displacing fentanyl from the mu-opioid receptor, as Buprenorphine’s binding affinity is 6.2 times higher than fentanyl’s [2]
Administering Buprenorphine via injection, a sublingual tablet, or as a transdermal patch between 12 – 24 hours after last fentanyl use [1]
Taking an initial stabilisation dose (8 – 16mg per day), followed by a 2mg reduction every 2 – 3 days for a 10 – 14-day detox [1]

Symptom management is used during fentanyl withdrawal by administering the Short Opioid Withdrawal Scale 1 – 2 times daily and providing medication as needed to alleviate:

Diarrhoea with 4mg Loperamide, followed by 2mg after each loose stool for up to five days; patients receive up to 16mg daily [3]
Nausea and vomiting with 10mg metoclopramide every 8 hours for a maximum of 5 days or 5mg prochlorperazine 3 times daily [3]
Stomach cramps with 135mg mebeverine 3 times a day and 7.5mg zopiclone at bedtime for agitation, anxiety and insomnia [3]
Muscular pains and headaches with paracetamol or aspirin, whilst encouraging at least 2 litres of water daily to replace fluids lost through perspiration or diarrhoea [3]

Physical Symptoms Of Fentanyl Detoxification

Pupil Enlargement

Pupil enlargement is a physical symptom of fentanyl withdrawal due to a 109.2% increase in noradrenaline, resulting in a 25% increase in pupil diameter within 8 - 24 hours of cessation [4] [5].

Pupil dilation lasts between 4 - 10 days after fentanyl discontinuation, although pupil diameter typically returns to baseline levels within 6 – 24 hours of buprenorphine administration [6] [7].

Pupil size is evaluated and scored daily using the Clinical Opiate Withdrawal Scale (COWS) during fentanyl detoxification (e.g. 5 = Pupils are so dilated that only the rim of the iris is visible) [1].

Muscle And Bone Pain

Muscle and bone pain are physical symptoms of fentanyl withdrawal due to an 87% increase in spontaneous GABAergic inhibitory postsynaptic activity in the brain [8].

Animal studies have found that fentanyl withdrawal increases pain sensitivity by 115.7% due to a 30% reduction of the nociceptive threshold within 8 - 24 hours of cessation [9] [10].

Muscle and bone pain is exacerbated by fentanyl-induced hyperalgesia and typically lasts between 1 – 4 weeks after the onset of withdrawal; pain severity is assessed daily using [11]:

The Clinical Opiate Withdrawal Scale (COWS): 0 = Muscle and Bone pain is not present vs 4 = Patient rubbing muscles and unable to sit still due to discomfort [1]
The Clinical Institute Narcotic Assessment (CINA): 3 = Intense muscle pain; muscles in legs, arms, or neck in a constant state of contraction [1]

Gastrointestinal Issues

Diarrhoea and vomiting are physical symptoms of fentanyl withdrawal due to a 95% reduction in mu receptor availability in the hypothalamus, leading to [12]:

A 69.3% reduction in constipation and a 12.98% increase in diarrhoea within 1 – 3 days, after experiencing a 15.5-minute delay in the rate of gastric emptying during active use [13] [14]
Stomach cramps caused by a 10 - 30% increase in the mean contraction frequency and amplitude in the Sphincter of Oddi after fentanyl use [15]

The severity of diarrhoea, vomiting and stomach cramps are assessed daily using CINA (e.g. 2 = Crampy abdominal pain; diarrhoea; active bowel sounds, 4 = Intermittent nausea with dry heaves) [1].

Heart Rate Changes

A 10% increase in heart rate is a physical symptom of fentanyl withdrawal due to a 109.2% increase in noradrenaline during withdrawal [4] [5].

Elevated heart rate persists for around 4 days and gradually returns to baseline levels within 1 week; 43% experience tachycardia at least once (heart rate >100 bpm) during fentanyl withdrawal [16].

Changes in heart rate are assessed and scored daily during fentanyl detoxification using COWS (0 = 80 or below, 1 = 81 – 100, 2 = 101 – 120, 4 = >120) [1].

Breathing Rate Changes

A 6% increase in breathing rate (15.1 to 16.0 breaths per min) is a physical indicator of fentanyl withdrawal due to [5]:

The reversal of fentanyl-induced respiratory depression resulting in bradypnea (<12 breaths per min), and decreased oxygen saturation <90% in some cases [18]
Opioid overdose reversal medications (e.g. 0.4mg/ml - 5mg/ml intramuscular naloxone) are administered to patients with shallow breathing (e.g. <10 breaths per minute) [1] [19]

Respiratory rate and oxygen saturation checks are conducted every 15 minutes – 1 hour during fentanyl detoxification; patients are monitored for up to 6 hours after medication is administered [20].

Psychological Symptoms Of Fentanyl Detoxification

Agitation And Irritability

Agitation and Irritability are psychological symptoms of fentanyl withdrawal due to a 37% reduction in dopamine activity, leading to [21]:

Restlessness in 35%, anxiety in 32%, and agitation in 14%, developing within 8 – 24 hours of cessation and peaking in severity between days 2 – 3 [16] [22]
Agitation and Irritability typically return to baseline levels by day 7 after buprenorphine binds to mu receptors to increase dopamine release by 25% [23]

Daily observations using CIWA-Ar and COWS assess the severity of agitation and irritability during fentanyl detoxification (e.g. ‘normal’ activity vs pacing back and forth, fidgety and restless [1].

Emotional Hypersensitivity

Emotional Hypersensitivity is a psychological symptom of fentanyl withdrawal due to the reversal of emotional suppression caused by an 85 – 95% inhibition of noradrenaline uptake during active use [24]:

Emotional hypersensitivity develops within 8 – 24 hours of cessation and eases within 1 week due to the reactivation of hypothalamus-pituitary-adrenal (HPA) axis functioning [25]
Dysphoria, low mood, anxiety and irritability are likely to be exacerbated in 42% - 44% of patients with co-occurring depression, anxiety, PTSD or OCD [22]

Patients receive daily mental status examinations during fentanyl detoxification to mitigate the 699% increased risk of suicidal behaviour (after >1 year of use) caused by mood instability during withdrawal [1] [26].

Hallucinations

Hallucinations are a psychological symptom of fentanyl withdrawal due to the overactivation of dopaminergic pathways in the brain, resulting in tactile, auditory and visual disturbances within 24 hours of cessation, lasting between 5 - 28 days [27].

Hallucination severity is assessed and scored daily using CIWA-ar, as disturbances are likely to be exacerbated in the 20% of fentanyl patients with pre-existing psychosis [22]:

0 = None
1 = Mild itching, pins and needles, burning or numbness
3 = Moderate sensitivity to light, colour changes
7 = Continuous hallucinations [1]

Hallucinations during fentanyl withdrawal are treated with >2.5mg haloperidol or 2 – 15mg diazepam daily, depending on patient need [28] [29].

Insomnia

Insomnia is a psychological symptom of fentanyl withdrawal due to hyperarousal of the central nervous system, increasing noradrenaline by 109.2% after being inhibited during active use [4].

Insomnia develops within 8 – 24 hours of fentanyl cessation and is exacerbated by changes in body temperature (e.g. chills/flushing), heart rate > 100, pain sensitivity and agitation at night [1].

Insomnia may last up to 12 months due to ataxic respiration in 61 – 92% and central sleep apnea (>10 second absence of airflow) in 24% of fentanyl users [30] [31].

Fentanyl Detox Recovery Markers

Fentanyl detox reduces pain perception by 48.8% due to the administration of buprenorphine and adjunctive medication (e.g. 2mg tizanidine 3 times daily) within 48 hours of fentanyl cessation [41]:

Self-reported pain levels decrease by 30.7% from day 1 to day 7 of fentanyl detox, after peaking between days 2 – 4 [16]
Initial pain sensitivity exacerbated by a 30% reduction of the nociceptive threshold for up to 5 days, typically returns to baseline levels within 1 month [10] [41]

Fentanyl detox improves cognitive processing speed and executive functioning scores by up to 11% within 6 months, as the 152% increased risk of cognitive impairment during active use is diminished by replacing fentanyl with buprenorphine [42] [43].

Neuropsychological functioning scores (e.g. learning and memory) improve by 4% within 7 – 14 days of fentanyl detox after experiencing forgetfulness (46%) and a lack of concentration (30%) during active use [42] [43].

Fentanyl Detoxification Timeline

Fentanyl Detox Timeline	Patient Presentation	Medical Interventions
24 - 48 Hours	Anxiety Insomnia Sweating Muscle Aches Dilated Pupils	Up to 8mg of Buprenorphine daily 0.1 - 0.3 mg Clonidine every 6 to 8 hours Paracetamol or Aspirin 135mg mebeverine 3 times daily
2 - 6 Days	Vomiting Nausea Diarrhoea Heart rate > 100	Stabilisation Buprenorphine doses for up to 1 week (8 - 16mg daily) Up to 16mg of Loperamide daily 10mg metoclopramide every 8 hours
7 - 10 Days	Depression Anxiety/ Irritability Insomnia Fatigue	Symptom management as needed e.g. 7.5mg zopiclone for persisting insomnia Buprenorphine taper over 3 - 6 days (2mg reductions)

How Does Cross-Tolerance Change Fentanyl Detoxification?

Cross tolerance to methadone changes fentanyl detoxification by extending the duration of withdrawal by up to 12 months, rather than 7 – 14 days for fentanyl alone due to [1]:

A methadone taper for at least 1 week to reach 30mg daily or less before buprenorphine is initiated (e.g. day 1 = up to 8mg, day 2 = up to 16mg, > day 3 = up to 32mg) [1]
Methadone and Fentanyl patients must wait 48 hours after the last methadone dose before an initial 2mg Buprenorphine dose is administered, rather than 12 – 24 hours for fentanyl alone [1]
Withdrawal symptoms typically begin after 24 – 72 hours of methadone cessation compared to 8 – 24 hours for fentanyl, peaking in severity during days 5 - 7 rather than 36 – 72 hours [1]

Buprenorphine completely alleviates withdrawal symptoms in 38.4% of fentanyl users after 24 – 72 hours of cessation and 40% of methadone users after 30+ hours of cessation from a daily dose <50mg [32] [33].

89% of methadone patients switching to buprenorphine require treatment for over 7 days, as 21% return to methadone within 1 week of attempted transfer due to moderate/severe withdrawals (COWS > 25) [34].

How Do Synthetic Analogues Change Fentanyl Detoxification?

Fentanyl being cut with carfentanil changes fentanyl detoxification by increasing the risk of fatal overdose by 107% due to being 100 times more potent than fentanyl alone [35] [36]:

Withdrawal symptoms typically develop around 6 hours after cessation from fentanyl mixed with carfentanil, peak in severity around day 3 and last between 1 – 2 weeks
Ongoing monitoring for slow respirations (<10 breaths per min) and pulse (<40 per min) is provided by staff trained to detect/treat apnea with assisted ventilation if required [37]
0.4 - 2.0mg Naloxone is used to reverse extreme drowsiness and a loss of consciousness or detox is arranged to take place in a hospital environment for 12+ hours of observations if necessary [38]

How Does Seizure Risk Change Fentanyl Detoxification?

Groups	Seizure Risk	How Does This Change Fentanyl Detox?
Traumatic Brain Injury	10% more likely to have a seizure compared to non-injured patients 86% have a 2nd seizure within 2 years due to posttraumatic epilepsy in up to 50% [38]	Monitoring for therapeutic plasma levels of anti-epileptic medications e.g. Carbamazepine Neurologic evaluations e.g. computerised tomography and electroencephalogram [36]
Autism Spectrum Disorder	Up to 22% have epilepsy and experience the 1st seizure by age 10 Increases the risk of recurrent seizures by 60% within 10 years [39]	Structured treatment in a calm/well-lit environment, providing Zopiclone or Melatonin to minimise seizures triggered by: Insomnia and flashing lights Changes in environment and daily routine e.g. meal times, location
Co-occurring Benzodiazepine Dependence	Benzodiazepines reduce seizure frequency by up to 75% by binding to GABA receptors [40]	Simultaneous detox with lower daily buprenorphine dose e.g. 2 mg rather than 16 mg to prevent overdose/respiratory depression [1]

Fentanyl Detoxification at Abbeycare

Fentanyl detoxification at Abbeycare is provided as part of a 28-day fentanyl rehab programme to address psychological and physical withdrawal symptoms using:

4 – 32mg Buprenorphine daily for up to 14 days to displace fentanyl from the mu-opioid receptor and completely alleviate withdrawal symptoms in up to 40% of patients [1] [32]
COWS and FDA-approved medication to assess and treat diarrhoea, insomnia and stomach cramps developing within 8 - 72 hours of cessation [1]

References

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[27] Guo, Song, et al. “Lofexidine versus Diazepam for the Treatment of Opioid Withdrawal Syndrome: A Double-Blind Randomized Clinical Trial in Singapore.” Journal of Substance Abuse Treatment, vol. 91, Aug. 2018, pp. 1–11. Accessed 22 Jan. 2025.“The initial dose of diazepam started from 10 mg on day 1 was increased to 15 mg peak dose on days 3 and 4, and gradually tapered down to 2 mg until day 10.”
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[32] Banys, Peter, et al. “An Open Trial of Low Dose Buprenorphine in Treating Methadone Withdrawal.” Journal of Substance Abuse Treatment, vol. 11, no. 1, Jan. 1994, pp. 9–15. Accessed 23 Jan. 2025.“Responses among the 15 subjects were: six, complete response; four, partial response; and five, no response to the administration of standard analgesic doses (0.15 to 0.30 mg) of sublingual buprenorphine.”
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[43]. Scott, Travis M., et al. “Neuropsychological Function Is Improved among Opioid Dependent Adults Who Adhere to Opiate Agonist Treatment with Buprenorphine-Naloxone: A Preliminary Study.” Substance Abuse Treatment Prevention and Policy, vol. 12, no. 1, BioMed Central, Nov. 2017. Accessed 17 Feb. 2025. “Table 4.”

About the author

Mischa Ezekpo

Mischa Ezekpo has a Bachelors degree in Psychology from Northumbria
University, and a Masters degree in Childhood Development and
Wellbeing, from Manchester Metropolitan University. Since 2018, Mischa
has written and published work on Addiction, Mental Health, Depression, and Eating Disorders. Content reviewed by Laura Morris (Clinical Lead).

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Last Updated: October 31, 2025