NCT07369089

Targeting Treatment-Resistant OUD With Ketamine-Assisted Mindfulness Oriented Recovery Enhancement

KETAMORE: TARGETING TREATMENT-RESISTANT OUD WITH KETAMINE-ASSISTED MINDFULNESS-ORIENTED RECOVERY ENHANCEMENT

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 88 (estimated)
• Sponsor: University of California, San Diego · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to examine the usefulness of Mindfulness-Oriented Recovery Enhancement combined with Ketamine-Assisted Psychotherapy (KetaMORE) for individuals with opioid use disorder who are receiving medication treatment. The main question it aims to answer is whether individuals with opioid use disorder who receive Mindfulness-Oriented Recovery Enhancement in combination with Ketamine-Assisted Psychotherapy will demonstrate greater reductions in opioid use and craving than individuals who receive Ketamine-Assisted Psychotherapy with a non-mindfulness support group. Participants will be randomly assigned to receive either Mindfulness-Oriented Recovery Enhancement combined with Ketamine-Assisted Psychotherapy or Ketamine-Assisted Psychotherapy combined with a support group control condition. Researchers will compare these groups on days of opioid use, time to first opioid use lapse, craving, and mood, assessed using ecological momentary assessments and standardized measures collected during treatment and follow-up.

Detailed description

This study is a Phase II, two-arm, parallel randomized controlled trial designed to evaluate the efficacy of Mindfulness-Oriented Recovery Enhancement combined with Ketamine-Assisted Psychotherapy (KetaMORE) compared to Ketamine-Assisted Psychotherapy paired with a support group control condition for individuals with opioid use disorder receiving medications for opioid use disorder (MOUD), including buprenorphine. Participants will be randomized in a 1:1 ratio to one of two conditions: (1) Ketamine-Assisted Psychotherapy combined with Mindfulness-Oriented Recovery Enhancement, or (2) Ketamine-Assisted Psychotherapy combined with a support group providing nonspecific therapeutic support without mindfulness training. Both groups will receive identical ketamine dosing and psychotherapy components; the conditions will differ only in the adjunctive behavioral intervention. Mindfulness-Oriented Recovery Enhancement is a manualized, evidence-based intervention integrating mindfulness training, cognitive reappraisal, and savoring techniques to reduce craving, negative affect, and maladaptive reward processing associated with substance use. The support group control condition is designed to match therapist contact and group support while excluding mindfulness-based content. Participants will complete assessments at baseline, during treatment, post-treatment, and follow-up. Primary outcomes will include number of days of opioid use and time to first opioid use lapse. Secondary outcomes will include opioid craving and mood symptoms. Ecological momentary assessments will be used to capture daily fluctuations in substance use, craving, and affect throughout the study period.

Conditions

• Opioid Use Disorder

Interventions

Type	Name	Description
DRUG	Ketamine	Ketamine will be administered as part of ketamine-assisted psychotherapy under medical supervision according to the study protocol. Ketamine dosing and administration procedures will be identical across study arms.
BEHAVIORAL	Mindfulness-Oriented Recovery Enhancement (MORE)	Mindfulness-Oriented Recovery Enhancement is a manualized, evidence-based intervention integrating mindfulness practices, cognitive reappraisal, and savoring exercises to reduce craving, improve emotional regulation, and support recovery from opioid use disorder. MORE sessions are delivered in a group format and coordinated with ketamine-assisted psychotherapy sessions.
BEHAVIORAL	Support Group	The support group intervention consists of therapist-led group sessions focused on emotional support and discussion of recovery-related experiences. This condition is designed to match the MORE intervention in duration and therapist contact while excluding mindfulness-based or structured skills training.

Timeline

• Start date: 2026-02-01
• Primary completion: 2028-01-01
• Completion: 2028-04-01
• First posted: 2026-01-27
• Last updated: 2026-02-03

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study