Summary of non-experimental human studies on the opioid withdrawal syndrome

Note that only outcomes directly related to opioid withdrawal severity are discussed. Studies may have reported additional outcomes not presented here.

ReferenceSystemMedicationStudy TypeSample SizeMaleResult
Alper et al. (1999)Multiple mechanismsIbogaineRetrospective chart review3367Ibogaine (mean = 19.3 ± 6.9 mg/kg) reduced withdrawal severity within 24 hours among 75% of individuals.
Birch (1889)CannabisCannabisCase report1100Cannabis reduced opioid withdrawal severity.
Brown and Alper (2018)Multiple mechanismsIbogaineProspective cohort study3083Ibogaine (mean = 1540 ± 920) reduced SOWS ratings from mean = 31 to mean = 14 within 3 days. Fifty percent of individuals reported opioid abstinence at 1-month follow-up.
Davis et al. (2017)aMultiple mechanismsIbogaineSurvey (online)8873Individuals stated ibogaine reduced or eliminated withdrawal symptoms (80% of respondents), led to sustained opioid abstinence (30%), and produced sustained reductions in opioid craving (25%).
Epstein and Preston (2015)CannabisCannabisSecondary outcome from RCT11653Participants completing a methadone-assisted taper (10-weeks) who did (n = 46) or did not (n = 70) provide a urine sample testing positive for cannabis during the treatment did not vary in their ratings of opioid withdrawal severity during the parent trial.
Gossop et al. (1991)CannabisCannabisRetrospective chart review5070Cannabis increased (24% of respondents) or decreased (12%) opioid withdrawal severity.
Lalanne et al. (2016)bMultiple mechanismsKetamineCase report10Patient reported ketamine (1 mg/kg) successfully assisted taper off opioid medications.
Malcolm et al. (2018)Multiple mechanismsIbogaineRetrospective chart review5061Ibogaine (dose NR) eliminated ratings on COWS (78% of individuals), SOWS (68%), and opioid craving (79%) 2 days after abrupt opioid discontinuation.
Pinkofsky et al. (2005)Multiple mechanismsQuetiapineSurvey (quality assurance)10745Quetiapine reduced cravings (74% of individuals), anxiety (49%), somatic pain (22%), and insomnia (21%), and improved appetite (13%). Only 4% felt quetiapine had no effect.
Quinlan (2012)aMultiple mechanismsKetamineCase report11NRPatients who received ketamine-assisted opioid detoxification reported ketamine was well-tolerated. Patients reported feeling better after 2 months (73% of respondents) and remained abstinent from opioids at 6 months (27%).
Sheppard (1994)Multiple mechanismsIbogaineCase report771Ibogaine (700–1800 mg) reduced opioid withdrawal severity at 24–38 hours.
Strickler et al. (2018)bMultiple mechanismsKetamineCase report1100Ketamine (10 mg/h infusion) + clonidine patch used to successfully taper patient off opioids over 7-day period.
Wakim (2012)bSerotoninOndansetronCase report10Ondansetron (16 mg/day) used to successfully taper patients off opioids over 10-day period.
Zullino et al. (2002)GlutamateTopiramateCase report367Topiramate (up to 500 mg/day) used to successfully taper patients off opioids over 9–14 day period.
  • COWS, clinical opiate withdrawal scale; NR, not reported; RCT, randomized controlled trial; SOWS, subjective opiate withdrawal scale.

  • a Patient population had chronic opioid use (population unspecified).

  • b Patient population comprised of persons with acute or chronic pain and opioid use disorder.