Clinical TrialOpioid Use Disorder (OUD)KetaminePlaceboRecruiting

Ketamine for Opioid Use Disorder

This randomised, quadruple-blind, placebo-controlled Phase II trial (n=50) will assess the effects of ketamine (52.5mg/70kg; 0.75 mg/kg IM, four doses over two weeks) on opioid craving and withdrawal symptoms in adults newly entering methadone treatment for opioid use disorder.

Target Enrollment
50 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

Randomised, quadruple-blind, parallel-group Phase II trial comparing IM ketamine (0.75 mg/kg, four doses over two weeks) with an active placebo (diphenhydramine 50 mg IM) in adults initiating methadone for opioid use disorder (n≈50).

Primary outcomes assess opioid craving and withdrawal symptoms; secondary outcomes include depression, pain, sleep quality, retention in methadone treatment, and safety assessed acutely and over 90 days of follow-up.

Study Protocol

Preparation

sessions

Dosing

4 sessions
120 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Four IM doses of ketamine (0.75 mg/kg) over two weeks; monitored 2 h post-dose.

Interventions

  • Ketamine0.75 mg/kg
    via IM• four doses over two weeks• 4 doses total

    First session must occur no later than 28 days post-intake; monitored 2 hours post-dose.

Active placebo

active

Four IM doses of diphenhydramine 50 mg as active placebo over two weeks; monitored 2 h post-dose.

Interventions

  • Placebo50 mg
    via IM• four doses over two weeks• 4 doses total

    Diphenhydramine 50 mg IM (active placebo); monitored 2 hours post-dose.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Age 18 to 65 years old
  • 2. Recent history (most recent 2 weeks prior to clinic intake) of routine use of illicit opioids, 5+ times/week
  • 3. Fulfillment of DSM-5/ICD-10 criteria for moderate-to-severe opioid use disorder
  • 4. Acceptance into methadone treatment for opioid use disorder within the past 14 days at the time of screening.

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Routine use of prescribed medications for OUD (5+ days/week) for longer than the 14 days leading up to clinic intake. Source: Self-report, H&P
  • 2. Recent prescribed or illicit benzodiazepine, ketamine, or PCP use that exceeds 5+ days/week for the last 3 months. Source: H&P
  • 3. Pregnant and/or breastfeeding. Source: UDS, H&P
  • 4. Stage 4 Hypertension, defined by a systolic blood pressure (SBP) > 180 mmHg or a diastolic blood pressure (DBP) > 120 mmHg. Source: H&P
  • 5. Clinically significant abnormal findings for which study participation is deemed unsafe. Source: H&P
  • 6. Severe mental illness or psychiatric disorder for which study participation is deemed unsafe (except for depression, PTSD, and substance use disorder). Source: H&P
  • 7. Severe hepatic impairment (baseline alkaline phosphatase or aspartate aminotransferase > 5 times the upper limit of normal). Source: Labs
  • NOTE: Due to time constraints in the study design, exclusion criterion #7 does not need to be met before the initial consent to participate. This criterion only needs to be established prior to the first esketamine/placebo session. This will allow us to enroll participants as soon as possible, giving more time and flexibility to complete the baseline/weekly assessments before the first esketamine/placebo session. Individuals that are initially enrolled and subsequently do not qualify due to severe hepatic impairment will be considered screen failures and withdrawn from the protocol.

Study Details

  • Status
    Recruiting
  • Phase
    Phase II
  • Type
    interventional
  • Design
    Randomizedquadruple Blind
  • Target Enrollment50 participants
  • Timeline
    Start: 2025-08-01
    End: 2029-08-31
  • Compounds
    KetaminePlacebo
  • Topic
    Opioid Use Disorder (OUD)

Locations

University of Maryland Addiction Programs and Affiliated Clinics — Baltimore, Maryland, United States

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