Ketamine for Opioid Use Disorder

Overseen By Kynah Walston, MA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Must be taking: Methadone

Must not be taking: Benzodiazepines, Ketamine, PCP

Disqualifiers: Pregnancy, Hypertension, Severe mental illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 2 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether ketamine, an anesthetic, can reduce opioid cravings and ease withdrawal symptoms such as depression, pain, and poor sleep. The researchers aim to determine if low doses of ketamine help individuals remain in methadone treatment longer and achieve better outcomes. Participants will receive either a low or very low dose of ketamine over two weeks and attend regular follow-ups for 90 days. The trial seeks adults who have frequently used illicit opioids in the past two weeks and have recently started methadone treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have been using prescribed medications for opioid use disorder or certain other drugs like benzodiazepines, ketamine, or PCP frequently in the past few months.

Is there any evidence suggesting that ketamine is likely to be safe for humans?

Research shows that ketamine, commonly used for anesthesia and treating depression, is being explored as a treatment for opioid use disorder (OUD). Studies suggest that ketamine might help reduce cravings for opioids and ease withdrawal symptoms like depression and trouble sleeping.

Regarding safety, some research indicates that ketamine is generally well-tolerated at low doses. However, side effects can include changes in heart rate or blood pressure, and in rare cases, more serious effects like confusion or muscle issues. These serious effects are uncommon, especially at low doses.

Other studies have safely used ketamine in different treatments, supporting its potential safety for OUD. This trial is in an early stage, so researchers are still collecting safety information. The low doses used in this study aim to minimize risks while exploring ketamine's benefits for opioid use disorder. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for opioid use disorder?

Researchers are excited about using ketamine for opioid use disorder because it offers a unique approach compared to standard treatments like methadone or buprenorphine, which primarily target opioid receptors. Ketamine acts on the NMDA receptors in the brain, offering a different mechanism that could potentially reduce cravings and withdrawal symptoms in a novel way. Additionally, ketamine is known for its rapid effects, which means it might help patients feel better faster than some current options that take longer to show results. This could make ketamine a game-changer in providing more immediate relief for those battling opioid dependency.

What evidence suggests that ketamine might be an effective treatment for opioid use disorder?

Studies have shown that ketamine can reduce cravings for opioids and lower their use in people with opioid use disorder (OUD). It has also eased withdrawal symptoms such as depression, pain, and poor sleep. Research indicates that ketamine improves the chances of staying off opioids compared to other treatments. In this trial, participants will receive either a very low dose of ketamine or a standard dose, both given intramuscularly. In some cases, ketamine has helped people remain in methadone treatment longer. These findings suggest ketamine may be a promising option for those struggling with OUD. ^{2 6 7 8 9}

Who Is on the Research Team?

Peter Manza, PhD

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

This trial is for adults with opioid use disorder who are starting methadone treatment. Participants must be in good general health and not have any serious psychological conditions, unstable medical issues, or a history of ketamine allergy.

Inclusion Criteria

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 14 days at the time of screening.

Exclusion Criteria

Pregnant and/or breastfeeding. Source: UDS, H&P

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

Clinically significant abnormal findings for which study participation is deemed unsafe. Source: H&P

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ketamine or placebo 4 times over a period of 2 weeks

2 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Weekly and monthly visits for checkups and tests

Long-term follow-up

Participants' treatment outcomes are assessed at 6, 9, and 12 months post-intake

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine

Trial Overview

The study tests if ketamine can reduce opioid cravings and withdrawal symptoms like depression, pain, and poor sleep in patients compared to an active placebo during the first two weeks of methadone treatment.

How Is the Trial Designed?

Group I: Treatment with Ketamine Experimental Treatment 1 Intervention

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.

Group II: Treatment with Very Low Dose Ketamine Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

Ketamine has been found to be an effective treatment for chronic pain conditions, including cancer-related neuropathic pain, and can help reduce the need for opioids by counteracting opioid-induced hyperalgesia.

At sub-anesthetic doses, ketamine demonstrates a significantly improved safety profile and fewer adverse events compared to its use as an anesthetic, making it a promising option for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine Use for Cancer and Chronic Pain Management. Culp, C., Kim, HK., Abdi, S.[2021]

There is currently no standardized safety monitoring protocol for off-label use of generic ketamine, and safety monitoring for intranasal esketamine varies by jurisdiction, leading to potential gaps in patient safety.

The Ketamine Side Effect Tool (KSET) is recommended as a comprehensive tool for monitoring both acute and long-term side effects of ketamine and esketamine treatments, addressing the lack of agreed frameworks for safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. Bayes, A., Short, B., Zarate, CA., et al.[2023]

In a systematic review of 93 studies involving 3756 participants receiving sub-anesthetic doses of ketamine for psychiatric disorders, only four serious adverse medical events (MSAEs) were reported, resulting in an incidence of approximately 0.1%, indicating a very low risk of serious complications.

No serious cardiac events or deaths were observed, and most studies effectively screened out high-risk patients, suggesting that with proper medical screening, ketamine can be administered safely for psychiatric treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the incidence of medical serious adverse events in sub-anesthetic ketamine treatment of psychiatric disorders. Hovda, N., Gerrish, W., Frizzell, W., et al.[2023]

This systematic review analyzed 60 studies on the safety of ketamine for treating depression, revealing that acute doses of ketamine led to more frequent side effects, including psychiatric and cardiovascular issues, compared to placebo.

There is a notable lack of data on the long-term safety and effects of repeated ketamine dosing, highlighting the need for large-scale clinical trials to better understand its safety profile over extended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-effects associated with ketamine use in depression: a systematic review. Short, B., Fong, J., Galvez, V., et al.[2019]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12076012/

Ketamine in treating opioid use disorder and opioid withdrawal

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sciencedirect.com

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NCT06943859 | Ketamine for Opioid Use Disorder

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.

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In people with chronic pain and escalating opioid use, a single prolonged ketamine infusion reduced pain and opioid use over the next 6 months (Citation28).

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frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1552084/full

Ketamine in treating opioid use disorder and ...

Preliminary evidence demonstrates that ketamine may be helpful in treating OUD as well as serve as an adjunct during treatment of opioid withdrawal (OW).

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clinicaltrials.gov

clinicaltrials.gov/study/NCT06111339

Ketamine for OUD and Suicidal Ideation in the ED

The primary aim is to evaluate the safety of the ketamine treatment. The secondary aim is to determine the preliminary efficacy of opioid- and suicide-related ...

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Ketamine Toxicity - StatPearls - NCBI Bookshelf

Acute use of ketamine may rarely cause encephalopathy, seizures, or coma. Acute kidney injury, electrolyte abnormalities, liver failure, and rhabdomyolysis may ...