Low-dose ketamine to reduce opioid craving in people starting methadone
Ketamine for the Treatment of Opioid Use Disorder
This test gives adults starting methadone either a low or very low dose of ketamine to see if it reduces opioid craving and withdrawal symptoms.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 50 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | University of Maryland, Baltimore Academic / other |
| Locations | 1 site (Baltimore, Maryland) |
| Trial ID | NCT06943859 on ClinicalTrials.gov |
What this trial studies
Adults who recently began methadone for moderate-to-severe opioid use disorder will be randomized to receive either a low dose or a very low dose of ketamine four times over two weeks. Participants will attend weekly and monthly clinic visits and safety checks for 90 days after intake to measure opioid craving, withdrawal-related symptoms (including depression, pain, and sleep), and treatment retention. Safety monitoring includes vital signs and screening for psychiatric or cardiovascular contraindications. Outcomes in the two dosing groups will be compared to determine whether the higher low dose yields better craving reduction and retention without unacceptable side effects.
Who should consider this trial
Good fit: Adults aged 18–65 who recently started methadone for moderate-to-severe opioid use disorder and who used illicit opioids regularly in the two weeks before intake, and who meet the study's health requirements, are the intended participants.
Not a fit: People who are pregnant or breastfeeding, have uncontrolled hypertension, significant heart or lung problems, severe psychiatric illness, or who have been on prescribed OUD medication long-term are unlikely to benefit or may be ineligible.
Why it matters
Potential benefit: If successful, this approach could reduce opioid craving and withdrawal symptoms and help people stay in methadone treatment longer.
How similar studies have performed: Small pilot and randomized studies of ketamine for substance use disorders and for depression have reported promising reductions in craving and relapse in some cases, but larger randomized evidence specifically for opioid use disorder is still limited.
Eligibility criteria
Show full inclusion / exclusion 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 21 days at the time of screening
5. Adherence to lifestyle requirements for participation
Exclusion Criteria:
1. Routine use of prescribed medications for OUD (5+ days/week) for longer than the 14 days leading up to clinic intake
2. Pregnant and/or breastfeeding
3. \*\*Stage 2 Hypertension, defined by a systolic blood pressure (SBP) \> 140mmHg or a diastolic blood pressure (DBP) \> 90 mmHg
4. Abnormal oxygen saturation or abnormal heart rate (i.e. O2 saturation \<95%, or HR \<60 or \>100bpm)
5. Clinically significant abnormal findings for which study participation is deemed unsafe
6. Severe mental illness or psychiatric disorder for which study participation is deemed unsafe (except for depression, PTSD, and substance use disorder)
7. \*\*ALT/AST \> 3 x Upper Limit of Normal (ULN), ALP 2 x ULN, or total bilirubin \> 1.5 x ULN. Source: Labs
8. History of hypersensitivity to ketamine
9. Suicidal ideation with a plan or intent or suicidal behaviors as reflected in Columbia-Suicide Severity Rating Scale (C-SSRS)
10. Recent homicidal ideation or violent behaviors
11. Concomitant daily use of medications with significant CYP2B6 and CYP3A4 inhibition or induction effects that can interfere with metabolism of ketamine
12. Advanced cardiopulmonary disorders, including stroke, cardiac arrest, and myocardial infarction in the past year
13. History of aneurysmal vascular disease or dissection (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation
14. \*\*Clinically significant EKG abnormalities.
15. Current significant use (\>3 days/week) of barbiturates, sedative hypnotics, benzodiazepines, ketamine, or PCP (prescribed or illicit)
* NOTE: Due to time constraints in the study design, these exclusion criteria do not need to be met before the initial consent to participate. This criterion only needs to be established prior to the first ketamine 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.
Where this trial is running
Baltimore, Maryland
- University of Maryland Addiction Programs and Affiliated Clinics — Baltimore, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: Peter Manza, PhD — University of Maryland, Baltimore
- Study coordinator: Peter Manza, PhD
- Email: peter.manza@som.umaryland.edu
- Phone: 410-706-2814
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.