A Phase 2 interventional study of Ketamine Hydrochloride and Midazolam Hydrochloride in Substance Use Disorders, Substance Use and Methamphetamine Abuse, sponsored by University of Texas Southwestern Medical Center. Active, not recruiting at 5 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-09-21.
Sponsored by University of Texas Southwestern Medical Center · Phase 2, Interventional, and Treatment
This study aims to determine whether treatment response with IV ketamine is superior to treatment response with IV midazolam in adults with moderate to severe MUD.
The study design is a 12-week randomized, double-blind, controlled trial comparing intravenous (IV) ketamine against IV midazolam, delivered over six weeks in 120 adults with moderate to severe methamphetamine use disorder (MUD).
Effective management for methamphetamine use disorder (MUD) remains elusive, despite widespread misuse of this stimulant. Psychological interventions have demonstrated modest benefits, and relapse rates are high. There are currently no Food and Drug Administration (FDA)-approved pharmacotherapies for MUD. This study explores the efficacy, safety, and feasibility for intravenous (IV) ketamine as a treatment for MUD and will help to determine the effect size for a larger, multi-site trial of intravenous (IV) ketamine in MUD.
Participants will receive either IV ketamine (0.50mg/kg) or IV midazolam (0.02mg/kg) over 45 minutes per infusion for a total of eight (8) infusions over six (6) weeks. Medical management sessions with a study clinician will be provided to all participants once weekly (from Weeks 1 through 6).
The use of IV ketamine in this trial is consistent in dose (0.5 mg/kg) and duration of infusion (45-minute-long) to other studies of ketamine for psychiatric disorders (such as major depressive disorder and post-traumatic stress disorder, both of which are often comorbid in individuals with MUD) and substance use disorder. However, IV ketamine has not been directly evaluated as mono-pharmacotherapy in those with MUD yet.
Additionally, participants will be asked to participate in cognitive behavioral therapy (CBT) sessions once weekly (from Weeks 1 through 12) on a non-infusion day.
2,124 studies on the registry are indexed under Substance-Related Disorders; 393 are open to participants now.
This study's enrollment of 120 is above the median of 108 across 1,727 interventional studies indexed under Substance-Related Disorders.
Browse Substance-Related Disorders studies →University of Texas Southwestern Medical Center is the lead sponsor of 990 studies on the registry; 201 are open to participants now.
Of its 135 completed or terminated interventional studies of FDA-regulated products, 100 (74%) have results posted.
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Study participants must:
Exclusion criteria
Study participants must not:
Additional inclusion and exclusion criteria will be assessed by the study investigators at the screening visit.
Participants will receive IV ketamine (0.50mg/kg) dissolved in 0.9% sodium chloride in a total volume of 100mL and administered with an infusion pump at a constant rate over 40 minutes. IV ketamine will be administered 8 times over 6 weeks.
Drug: Ketamine Hydrochloride
Participants will receive IV midazolam (0.02mg/kg) dissolved in 0.9% sodium chloride in a total volume of 100mL and administered with an infusion pump at a constant rate over 40 minutes. IV midazolam will be administered 8 times over 6 weeks.
Drug: Midazolam Hydrochloride
Participants will receive IV ketamine (0.50mg/kg) dissolved in 0.9% sodium chloride in a total volume of 100mL and administered with an infusion pump over 45 minutes. Duration of each infusion may be extended by the Study Clinician supervising study medication infusion if slower infusion rate is better tolerated.
Also known as: Ketelar
Participants will receive IV midazolam (0.02mg/kg) dissolved in 0.9% sodium chloride in a total volume of 100mL and administered with an infusion pump over 45 minutes. Duration of each infusion may be extended by the Study Clinician supervising study medication infusion if slower infusion rate is better tolerated.
Also known as: Versed
Treatment Response
Defined as having at least three methamphetamine-negative urine samples out of four samples obtained during Weeks 3 and 4.
Time frame: 2 weeks
Non-serious adverse outcomes associated with IV ketamine treatment for methamphetamine use
Defined by non-serious adverse events (associated with the IV ketamine treatment) reported during the study intervention phase (weeks 1 to 6). Participants will be assessed for adverse events at each study visit.
Time frame: 6 weeks
Adherence to treatment
Defined by completion of at least five out of eight IV ketamine or IV midazolam infusions.
Time frame: 6 weeks
Total abstinence
Defined as four out of four methamphetamine-negative urine samples obtained during Weeks 3 and 4 (since missing urine drug screens will be counted as positive).
Time frame: 2 weeks
Abstinence from methamphetamine use
Defined by the self-reported days of methamphetamine use as reported on the Timeline Followback (TLFB) from Week 1 to Week 4, Week 5 to Week 6, and Week 7 to Week 12.
Time frame: 12 weeks
Differences in methamphetamine-negative urine samples from Weeks 1 to 6 and between ketamine and midazolam arms.
Urine samples will be collected twice a week at in-person visits.
Time frame: 6 weeks
Differences in methamphetamine-negative urine samples from Weeks 1 and 2 versus Weeks 3 and 4.
Urine samples will be collected twice a week at in-person visits.
Time frame: 4 weeks
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Plan to share: No
This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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University of Texas Southwestern Medical Center