Opioid Use DisorderPhase 2NCT06943859
Ketamine for Opioid Use Disorder
A Phase 2 study testing Treatment with Ketamine and Treatment with Very Low Dose Ketamine in people with Opioid Use Disorder, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn if ketamine works to reduce craving for opioids in adults enrolled in 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- Treatment with Ketamine and Treatment with Very Low Dose Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Feb 2026to 31 Aug 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 65 years old
- Fulfillment of DSM-5/ICD-10 criteria for moderate-to-severe opioid use disorder
- Acceptance into methadone treatment for opioid use disorder at the time of screening.
- Adherence to lifestyle requirements for participation.
- Self-reported craving greater than or equal to 20 out of 100 for opioids at any point in the past week at time of screening
- Positive UDS for opioids or self-reported illicit opioid use in the past three months at time of screening
Who cannot join
- Pregnant and/or breastfeeding.
- **Stage 2 Hypertension, defined by a systolic blood pressure (SBP) > 140 mmHg 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.
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- 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).
- 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. This will allow us to enroll participants as soon as possible, giving more time and flexibility to complete the baseline assessments before 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. Because repeated ketamine administration is associated with hepatobiliary dysfunction (most often a cholestatic pattern) we will also obtain a follow up LFT within 30 days of the final ketamine session.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Maryland Addiction Programs and Affiliated Clinics
Baltimore, Maryland, 21201
Peter Manza, PhD, 410-706-2814, peter.manza@som.umaryland.edu
About this study
Official title: Ketamine for the Treatment of Opioid Use Disorder
The goal of this clinical trial is to learn if ketamine works to reduce craving for opioids in adults enrolled in 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?
Read more
Researchers will compare two low doses of ketamine to see if ketamine works to reduce craving for opioids in adults enrolled in 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 with the study team one week prior to the first ketamine session, one week following the last ketamine session, at 30 days following the final ketamine session, and 90 days following the final ketamine session for checkups and tests
- Conditions
- Opioid Use Disorder
- Being tested
- Treatment with Ketamine, Treatment with Very Low Dose Ketamine
- Keywords
- opioid use disorder, ketamine, craving, treatment adherence, methadone
- Medical subject headings
- Opioid-Related Disorders, Treatment Adherence and Compliance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment with KetamineDrug
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 Very Low Dose KetamineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Treatment with Very Low Dose Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Collected at 7 days pre- and post-ketamine, 30-, and 90-days post-final ketamine session
Secondary outcomes (9)
Severity of depression symptoms
Montgomery-Asberg Depression Rating Scale (MADRS): a 10-item questionnaire of depression severity. The total score ranges from 0-60, with scores of 0-6 considered normal (non-depressed), 7-19 indicative of mild depression, 20-34 indicative of moderate depression, and 35-60 indicative of severe depression. Item 10 on the instrument will be used to monitor any changes in suicidal ideation throughout the trial.
Measured: Completed at 7 days pre- and post-ketamine, 30-, and 90-days post final ketamine session
Cue-induced craving scores
Cue Reactivity Paradigm: our drug cue reactivity paradigm will be designed to elicit an acute craving state. We will present a series of opioid cue images continuously (total time <5 min) via computer or tablet. Cues will be personalized based on each individual's drug use history as derived from baseline clinical assessments. For example, if a participant had no history of intravenous drug injection, we will not present opioid cue images containing injection paraphernalia like needles and instead will present images with opioid pills and/or powder. At the end of each one-minute session, participants will be asked to rate, on a scale of 1-10, "How much did you like the images you saw?", "How much do you want to use right now?", "How much do you want to avoid using right now?", "How much control do you feel you have over using right now" and "What is the maximum amount you would pay right now for a single dose of what you saw?"
Measured: Collected at 7 days pre- and post-ketamine, 7 days pre- and post ketamine, ketamine administration days, 30-, and 90-days post-final ketamine session
Chronic pain ratings
Graded Chronic Pain Scale (GCPS): a six-item instrument that evaluates chronic pain severity (intensity and impact on life activities).
Measured: Collected at 7 days pre- and post-ketamine, ketamine administration days, 30-, and 90-days post-final ketamine session
Number of methadone doses received at 90 days post final ketamine session
Study team will have access to clinic records to assess the number of methadone doses patients have received at 90 days post final ketamine session
Measured: Collected through 90 days post final ketamine session
Sleep quality ratings
Pittsburgh Sleep Quality Index (PSQI): A 19-item questionnaire assessing past-month sleep quality and disturbances. Seven component scores are generated: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for the 7 components yields one global score
Measured: PSQI collected at 7 days pre- and post-ketamine, 30-, and 90 days post-final ketamine session
Insomnia Symptoms
Insomnia Severity Index (ISI): A five-item measure of current (past two weeks, or since last study visit) insomnia symptoms.
Measured: Collected at 7 days pre- and post-ketamine, ketamine administration days, 30-, 90-days post-final ketamine session
Sleep quality ratings on a Visual Analogue Scale (VAS)
Modified Single Item Sleep Quality Scale (SQS): A self-administered questionnaire that incorporates a VAS delivered electronically. SQS directs the patient to rate the overall quality of sleep over a 7-day period (modified for our study to rate the overall quality of sleep the past night) on a scale of 1-10 considering how many hours of sleep they had, how easily they fell asleep, how often they woke up during the night (excluding bathroom trips), how often they woke up earlier than intended
Measured: SQS collected via daily optional EMAs through 7 days post final ketamine session, then every other day until 90 days post final ketamine session
Scores on a holistic measure of recovery
Substance Use Recovery Evaluator (SURE): A 21-item patient reported outcome measure of recovery from substance use disorder that has good face and content validity, acceptability and usability for people in recovery and is psychometrically valid.
Measured: Collected at 7 days pre- and post-ketamine, 30-, and 90 days post-final ketamine session
Frequency of negative urine drug screens through 90 days post final ketamine session
Study team will have access to clinic drug screenings through 90 days post-intake
Measured: collected through 90 days post final ketamine session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2025
- Study start4 Feb 2026
- Primary completion31 Aug 2028 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter Manza, University of Maryland, Baltimore
- Investigators
- Peter Manza, PhD, Principal investigator, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06943859
- Sponsor's protocol ID
- HP-00114026
- Status last verified
- Nov 2025
- First submitted
- 9 Apr 2025
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided