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

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

Trial Summary

What is the purpose of this trial?

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 ketamine stay in methadone treatment longer, and/or have better treatment outcomes than those given the placebo? Researchers will compare ketamine to an active placebo (a look-alike substance that contains a drug that does not do anything to help the condition it is supposed to treat but will mimic some of the side effects 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 ketamine or a placebo 4 times over a period of 2 weeks * Visit the clinic weekly and monthly for checkups and tests for 90 days post-intake

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.

What data supports the effectiveness of the drug ketamine for treating opioid use disorder?

Some studies suggest that ketamine, which is effective for treating depression, may also help reduce substance use in people with substance use disorders, including opioid use disorder, especially when combined with psychotherapy. ^{1 2 3 4 5}

Is ketamine generally safe for human use?

Ketamine has been used safely in humans at low doses for conditions like depression and chronic pain, with improved safety profiles compared to its use as an anesthetic. However, some side effects like changes in mood, heart issues, and nervous system effects have been reported, especially with repeated use. ^{6 7 8 9 10}

How is the drug ketamine unique for treating opioid use disorder?

Ketamine is unique for treating opioid use disorder because it can help reduce opioid use without causing respiratory depression (breathing problems) and may prevent hyperalgesia (increased sensitivity to pain) and central sensitization (increased response to pain). It is often used as an adjunct (additional treatment) to help taper off high doses of opioids while maintaining pain control. ^{1 4 11 12 13}

Research Team

Peter Manza, PhD

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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 Placebo Placebo Group 1 Intervention

Individuals will receive four doses spaced 1-6 days apart of an intramuscular active placebo (diphenhydramine, 50 mg) (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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Low-dose ketamine analgesia: patient and physician experience in the ED. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Ketamine for pain. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Mental health facilities with ketamine infusion therapy in the United States in 2020: Co-location of dual diagnosis mental health and substance use disorder treatment. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Impact of ketamine versus fentanyl continuous infusion on opioid use in patients admitted to a surgical-trauma intensive care unit. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Intraoperative S-ketamine for the reduction of opioid consumption and pain one year after spine surgery: A randomized clinical trial of opioid-dependent patients. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A systematic review of the incidence of medical serious adverse events in sub-anesthetic ketamine treatment of psychiatric disorders. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Ketamine Use for Cancer and Chronic Pain Management. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Side-effects associated with ketamine use in depression: a systematic review. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. [2023]

10. England pubmed.ncbi.nlm.nih.gov

BET 2: Safety and efficacy of low-dose ketamine versus opioids for acute pain management in the ED. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Use of Ketamine in a Multimodal Analgesia Setting for Rapid Opioid Tapering in a Profoundly Opioid-Tolerant Patient: A Case Report. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Opioid switching and burst ketamine to improve the opioid response in patients with movement-related pain due to bone metastases. [2013]

13. England pubmed.ncbi.nlm.nih.gov

The Enigma of Low-Dose Ketamine for Treatment of Opioid-Induced Hyperalgesia in the Setting of Psychosocial Suffering and Cancer-Associated Pain. [2019]