Ketamine-Assisted Recovery (KARE): protocol for an open-label pilot trial of ketamine-assisted psychotherapy for publicly insured patients with methamphetamine use disorder and HIV risks
Nicky J. Mehtani, B. Anderson, Irina Alexander, Peter S. Hendricks, Jennifer Mitchell, Phillip O. Coffin, Mallory O. Johnson
BMJ Open August 1, 2025 DOI: 10.1136/bmjopen-2025-100775 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Open-label pilot study Randomized Peer reviewed |
|---|---|
| Population | Medicaid-insured or Medicare-insured adults with moderate-to-severe methamphetamine use disorder and HIV risk factors |
| Interventions | Ketamine-assisted psychotherapy motivational enhancement therapy |
| Dose | 0.50-0.75 mg/kg |
| Duration | 5 weeks |
| Topics | Ketamine Esketamine Psychedelic-assisted therapy |
| Keywords | Protocol science Methamphetamine Open label Clinical trial Alternative medicine Family medicine |
| Registration | NCT06538285 |
| Key points | The KARE trial aims to assess feasibility, acceptability, tolerability, and safety of ketamine-assisted psychotherapy for methamphetamine use disorder, with no results yet reported. |
Abstract
Introduction: Methamphetamine use disorder (MeUD) is a debilitating condition with no FDA-approved pharmacotherapies that has been associated with poor neurological, psychiatric and cardiovascular outcomes, particularly among low-income populations. The use of methamphetamine also increases risks for sexually transmitted infections (STIs) by reducing behavioural inhibitions while enhancing sexual libido, disproportionately affecting sexual and gender minorities. The overlap of MeUD with HIV risks and psychological trauma underscores the need for innovative, accessible and culturally responsive therapies. Ketamine-assisted psychotherapy (KAP), which has shown promise for treatment-resistant depression and other substance use disorders, has yet to be explored for MeUD. The Ketamine-Assisted Recovery (KARE) trial seeks to address this gap.
Methods: AND ANALYSIS: KARE is an open-label pilot study enrolling N=12-24 Medicaid-insured or Medicare-insured adults with moderate-to-severe MeUD and HIV risk factors. Participants will undergo three office-based intramuscular ketamine (0.50-0.75 mg/kg) sessions in combination with seven sessions of motivational enhancement therapy over 5 weeks. Recruitment efforts target community-based organisations, outpatient clinics offering HIV and STI testing/treatment, and substance use disorder treatment programmes. Feasibility, acceptability and tolerability will be assessed via recruitment and a priori retention benchmarks, surveys and semistructured interviews exploring participants' perceptions of KAP and ketamine's misuse potential. Safety will be evaluated through systematic monitoring for adverse events and serial measurement of vital signs during dosing., craving, withdrawal, HIV risk behaviours and psychological distress, as well as psychological and cognitive flexibility as potential mechanisms of ketamine's effects, laying the groundwork for future randomised controlled trials. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the University of California, San Francisco Institutional Review Board (24-41588) and the Research Advisory Panel of California (202422S). Results will be disseminated through national conferences, peer-reviewed publications and presentations to community-based stakeholders.
Trial Registration: NUMBER: NCT06538285.
Comparable studies
Other non-randomized and open-label trials on ketamine and psychedelic-assisted therapy, most cited first.