Ketamine-Enhanced MORE Trial Reports Fewer Drug Use Instances

Key Takeaways

• MORE plus ketamine was associated with fewer drug use instances after treatment and lower craving at follow-up than MORE alone.
• No serious ketamine-related adverse events occurred, and between-group differences were not reported for distress or buprenorphine use.
• The ketamine arm showed larger gains in mindfulness-related processes, and full mystical experience was reported in association with lower opioid craving.

In a 68-participant single-blinded clinical trial involving people receiving buprenorphine for opioid use disorder, MORE plus intramuscular ketamine was associated with fewer drug use instances after treatment and lower craving at follow-up than MORE alone. Both groups received the same psychotherapy platform, allowing the between-group separation to center on the added ketamine component. The randomized comparison did not support treating the findings as definitive proof of efficacy, but the early signal favored the ketamine-augmented arm across the reported drug use and craving measures.

The trial randomly assigned 68 participants to MORE plus ketamine-assisted psychotherapy or to MORE alone in a direct parallel comparison. Mindfulness-Oriented Recovery Enhancement consisted of 8 weeks of mindfulness, reappraisal, and savoring training delivered through telehealth videoconferencing to both randomized groups. With the same core behavioral program in both groups, the study assessed the added contribution of ketamine augmentation. Participants in the ketamine arm received 0.5 mg/kg intramuscularly after week 5, followed one week later by a second dose up to 1.0 mg/kg. The prespecified primary outcome was instances of drug use, while secondary outcomes included craving, distress, affective states, and buprenorphine use.

Investigators found significantly fewer instances of drug use after treatment in the ketamine arm than in the MORE-only arm. They also reported lower craving at follow-up among participants assigned to ketamine augmentation alongside the shared psychotherapy program. By contrast, no between-group differences were reported for distress or buprenorphine use. Affective states remained part of the secondary outcome framework, although the abstract did not describe a comparative finding for that measure in either arm. The observed separation centered on drug use and craving rather than every measured outcome.

No serious ketamine-related adverse events occurred during the randomized comparison in participants receiving buprenorphine for opioid use disorder. Researchers also reported greater increases in mindfulness-related processes in the ketamine arm than in the psychotherapy-only group over the study course. During ketamine administration, 85% of participants reported a full mystical experience, which predicted reduced opioid craving. That process-related finding appeared alongside the clinical results after ketamine administration in this trial.

The abstract characterized the combined safety and outcome pattern as consistent with safety and preliminary efficacy.