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

Methamphetamine use disorder (MeUD) has no FDA-approved pharmacotherapies and is linked to poor neurological, psychiatric, and cardiovascular outcomes, especially among low-income populations, while also increasing risks for sexually transmitted infections. The Ketamine-Assisted Recovery (KARE) trial is an open-label pilot study enrolling 12 to 24 Medicaid- or Medicare-insured adults with moderate-to-severe MeUD and HIV risk factors. Participants will receive three intramuscular ketamine sessions (0.50-0.75 mg/kg) combined with seven motivational enhancement therapy sessions over five weeks. The study will assess feasibility, acceptability, tolerability, safety, and potential mechanisms such as psychological flexibility, laying groundwork for future randomized trials.

Study at a glance

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.