Ketamine for Opioid Use Disorder

NCT06943859 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HP-00114026
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if ketamine works to reduce craving for opioids in adults entering methadone treatment for opioid use disorder. The main questions it aims to answer are:

• Does ketamine reduce craving for opioids in patients with opioid use disorder?
• Does ketamine reduce symptoms of opioid withdrawal such as depression, pain, and poor sleep quality?
• Do patients who take the low dose ketamine stay in methadone treatment longer, and/or have better treatment outcomes than those given the very low dose? Researchers will compare two low doses of ketamine to see if ketamine works to reduce craving for opioids in adults entering methadone treatment for opioid use disorder. Participants will:
• Be given a low dose or a very low dose of ketamine 4 times over a period of 2 weeks
• Visit the clinic weekly and monthly for checkups and tests for 90 days post-intake

Conditions

Opioid Use Disorder

Keywords

opioid use disorder; ketamine; craving; treatment adherence; methadone

Outcome Measures

Primary Outcomes (1)

• Tonic craving (FORCAST) total scores

  Faceted Opioid Research Craving Assessment for Substance use Treatment (FORCAST): A 26-item assessment of tonic craving that the person reports having felt over the prior one or two weeks. Participants indicate how much they disagree or agree with each statement on a scale that ranges from 0-6, with 0 representing "strongly disagree", 3 representing "neither agree nor disagree", and 6 representing "strongly agree". Higher scores indicate higher levels of craving. The minimum score is 0, and the maximum scores for each of the subscales are as follows: Preoccupation: 24 Negative Reinforcement: 30 Positive Reinforcement: 24 Motivation: 30 Lack of control: 24 Uneasiness: 24 Maximum total score for all subscales = 156

  Collected at baseline, weekly, 30-, 60-, and 90 days post-intake

Secondary Outcomes (9)

• Severity of depression symptoms

  Completed at baseline, weekly, 30-, 60-, and 90 days post-intake

• Cue-induced craving scores

  Collected at Baseline, weekly following intake, 30-, 60-, and 90 days post-intake

• Chronic pain ratings

  Collected at Baseline, weekly following intake, 30-, 60-, and 90 days post-intake

• Number of methadone doses received at 90 days post-intake

  Collected through 90 days post-intake

• Sleep quality ratings

  PSQI collected at Baseline and 30-, 60-, and 90 days post-intake

Other Outcomes (3)

• Decision making test performance (risk and ambiguity tolerance)

  collected weekly through 90 days post-intake via optional EMAs

• Methadone dose (mg) at 90 days post-intake

  collected through 90 days post-intake

• OUD treatment outcomes at 6-, 9-, and 12 months post intake

  collected through 6-, 9-, and 12 months post intake

Study Arms (2)

Treatment with Ketamine

EXPERIMENTAL

Individuals will receive four doses spaced 1-6 days apart of 0.75mg/kg of intramuscular ketamine (n=25) over a period of two weeks.

Drug: Treatment with Ketamine

Treatment with Very Low Dose Ketamine

ACTIVE COMPARATOR

Individuals will receive four doses spaced 1-6 days apart of an intramuscular ketamine (0.1mg/kg) (n=25) over a period of two weeks.

Drug: Treatment with Very Low Dose Ketamine

Interventions

Treatment with Ketamine DRUG

Participants will receive four doses of ketamine spaced 1-6 days apart of 0.75 mg/kg intramuscular ketamine (n=25) for two weeks (first ketamine session must occur no later than 28 days post-intake). Individuals will be monitored for two hours post-dose by a clinician.

Treatment with Ketamine

Treatment with Very Low Dose Ketamine DRUG

Participants will receive four doses of very low dose ketamine (0.1mg.kg) (n=25) spaced 1-6 days apart for two weeks (first ketamine session must occur no later than 28 days post-intake). Individuals will be monitored for two hours post-dose by a clinician.

Treatment with Very Low Dose Ketamine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 65 years old
• Recent history (most recent 2 weeks prior to clinic intake) of routine use of illicit opioids, 5+ times/week
• Fulfillment of DSM-5/ICD-10 criteria for moderate-to-severe opioid use disorder
• Acceptance into methadone treatment for opioid use disorder within the past 21 days at the time of screening
• Adherence to lifestyle requirements for participation

You may not qualify if:

• Routine use of prescribed medications for OUD (5+ days/week) for longer than the 14 days leading up to clinic intake
• Pregnant and/or breastfeeding
• \*\*Stage 2 Hypertension, defined by a systolic blood pressure (SBP) \> 140mmHg or a diastolic blood pressure (DBP) \> 90 mmHg
• Abnormal oxygen saturation or abnormal heart rate (i.e. O2 saturation \<95%, or HR \<60 or \>100bpm)
• Clinically significant abnormal findings for which study participation is deemed unsafe
• Severe mental illness or psychiatric disorder for which study participation is deemed unsafe (except for depression, PTSD, and substance use disorder)
• \*\*ALT/AST \> 3 x Upper Limit of Normal (ULN), ALP 2 x ULN, or total bilirubin \> 1.5 x ULN. Source: Labs
• History of hypersensitivity to ketamine
• Suicidal ideation with a plan or intent or suicidal behaviors as reflected in Columbia-Suicide Severity Rating Scale (C-SSRS)
• Recent homicidal ideation or violent behaviors
• Concomitant daily use of medications with significant CYP2B6 and CYP3A4 inhibition or induction effects that can interfere with metabolism of ketamine
• Advanced cardiopulmonary disorders, including stroke, cardiac arrest, and myocardial infarction in the past year
• History of aneurysmal vascular disease or dissection (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation
• \*\*Clinically significant EKG abnormalities.
• Current significant use (\>3 days/week) of barbiturates, sedative hypnotics, benzodiazepines, ketamine, or PCP (prescribed or illicit)

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland Addiction Programs and Affiliated Clinics

Baltimore, Maryland, 21201, United States

RECRUITING

MeSH Terms

Conditions

Opioid-Related Disorders; Treatment Adherence and Compliance

Interventions

Therapeutics; Ketamine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Peter Manza, PhD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter Manza, PhD

CONTACT

410-706-2814; peter.manza@som.umaryland.edu

Kynah Walston, MA

CONTACT

443-974-7951; Kynah.Walston@som.umaryland.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: April 24, 2025
• Study Start: February 4, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2029
• Last Updated: March 13, 2026

Record last verified: 2025-11

Locations

US (1)