Ketamine-Assisted MORE For Opioid Use Disorder: RCT

The opioid use disorder is leading to several issues, and combinations of medication and psychotherapy approaches have gained much attention. There has been an innovative combination of psychotherapy sessions under the influence of ketamine and Mindfulness-Oriented Recovery Enhancement (MORE), which is a structured program using mindfulness techniques. This has been tested in a randomized controlled trial study recently, posing various concerns on the same.

Why It Matters

The opioid use disorder is leading to several issues, and combinations of medication and psychotherapy approaches have gained much attention. There has been an innovative combination of psychotherapy sessions under the influence of ketamine and Mindfulness-Oriented Recovery Enhancement (MORE), which is a structured program using mindfulness techniques. This has been tested in a randomized controlled trial study recently, posing various concerns on the same.

MORE or Mindfulness-Oriented Recovery Enhancement is a manualized treatment program that uses mindfulness training along with cognitive reappraisal and savoring of natural reinforcers in order to redirect an individual’s attention from drug cues to more adaptive stimuli of pleasure and coping. According to previous studies done through randomized controlled trials, MORE has shown efficacy in reducing craving and facilitating recovery in conjunction with existing standard treatment programs. This makes MORE an interesting choice for combining with novel therapies to re-regulate brain states or emotional responses.

Ketamine is a sedative and anesthetic drug with quick-acting psychoactive effects that has come to be used in recent times as an adjunct to psychotherapy, and in the treatment of severe depression or pain resistant to treatment. Ketamine’s effects on one’s psychological perception are believed to generate a therapeutic window wherein psychotherapy becomes more effective for some patients. However, the use of ketamine as a sedative and anesthetic drug comes with side effects, both short-term and in the long run. In recent years, more and more ketamine clinics are being set up and prescribed for off-label uses, making the integration of such a drug with programs like MORE pertinent.

Who It Affects

More immediately impacted are patients suffering from opioid use disorder but failing due to medication-assisted treatment programs, particularly individuals with ongoing craving tendencies, mood disturbance, or chronic pain. In this group of patients, the strategy seeks to decrease subjective cue-reactivity and promote improved self-regulation so that benefits persist post-pharmacologic effect. Those health professionals involved in the management of addiction, including specialists in addictions medicine, psychiatry, general practice, and pain management, will have to become familiar with proper screening and risk management practices should the protocols receive widespread adoption. (

Health systems, payers, and regulators are also stakeholders. If ketamine-assisted psychotherapy plus MORE proves clinically useful and safe, payers will face decisions about coverage for an intensive, multidisciplinary service that combines medication administration, monitored clinical time, and structured group or individual therapy. Regulators and safety monitors will need to weigh risks related to off‑label ketamine use, compounded formulations, and the growing commercial clinic market that has sometimes outpaced robust oversight. Those dynamics affect access, equity, and the potential for uneven quality of care across regions.

Lastly, staff issues have to be considered. The implementation of both ketamine and MORE therapy is dependent on properly trained personnel who can effectively utilize MORE as well as deliver ketamine therapy among those suffering from addiction. This kind of multidisciplinary training may not be easily available in smaller treatment centers, making large centers the more likely place for initial adoption.

What Changes

• Clinical application: The integration of a pharmacological procedure with a behavioral therapy protocol in ketamine-assisted MORE therapy presents an opportunity for clinicians to engage with a treatment protocol where there can be a combination of a pharmacological approach with a behavioral program aimed at enhancing emotional regulation and learning.
• Risk Management: Programs will require a specific protocol for choosing patients, cardiovascular and mental assessment, and follow-up to identify any adverse outcomes including transient dissociation, hypertension, or misuse. Obtaining informed consent and conducting harm reduction counseling becomes an integral part of treatment.
• Coverage and reimbursement: The issue of covering pharmacologic-behavioral treatment programs must be addressed by insurance companies and health care organizations. In cases where coverage is not available, such programs may only be accessible in specialized centers or during research studies.
• Training and policy: Regulators and professional organizations would have to create policies regarding best practices, training standards for clinicians, and quality metrics to guarantee safety and equity during roll out if this technique becomes more popular. It will become necessary to train more therapists and establish procedures for safely administering ketamine.

Going forward, a handful of pragmatic concerns must be considered to decide whether the ketamine-assisted MORE will evolve beyond the experimental stage and become a widespread form of adjunct treatment. These include sustainability: Is it possible to use the insights gained within a ketamine-supported therapeutic window for sustaining behavioral changes and minimizing opioid consumption? Also, safety: Clinical use will entail rigorous observation of negative effects, including the risk of dependence. Another challenge is scalability, in terms of training clinicians who would be able to conduct the therapy, as well as devising funding models for the therapy’s widespread use.

In terms of treatment choices currently made by clinicians, the pragmatic choice would be that of cautious optimism. Mindfulness-based therapies have a strong body of evidence as adjuvant therapies to pharmacological treatments and can be implemented wherever there is a possibility. The use of ketamine could be explored among selected patients under highly regulated circumstances, keeping in mind the potential cardiac and mental health dangers as well as the drug-taking history of the patient along with local laws and program requirements. Ketamine use, along with structured behavioral therapy rather than informal psychotherapy, could help sustain the benefits obtained during the session.

To summarize, the combination of a psychoactive pharmaceutical and a mindful methodology could represent an interesting approach for addressing the complicated issues of emotions anensd rewards that drive OUD. On the other hand, the new intervention would create new challenges and raise questions about its safe administration, training of professionals, funding, and availability to all groups that may benefit from it. Further steps should include the pilot introduction of the new methodology in clinical practice, consensus-based recommendations regarding safety issues, and policy making to prevent inequalities.

Refferences

1. Garland, E. L., Lewis, B. R., Thielking, P., Odette, M., Pfeffer, H., & Shen, J. (2026). Ketamine-assisted Mindfulness-Oriented Recovery Enhancement for opioid use disorder: A randomized controlled trial. Nature Mental Health. https://www.nature.com/articles/s44220-026-00625-5
2. National Library of Medicine. (2023). Ketamine Assisted Psychotherapy for Opioid Use Disorder (NCT04892251). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT04892251
3. Shen, M. R., Campbell, D. E., Kopczynski, A., Maddams, S., Rosenblum, N., Nigam, K., & Suzuki, J. (2025). Ketamine in treating opioid use disorder and opioid withdrawal: A scoping review. Frontiers in Psychiatry, 16, 1552084. https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1552084
4. National Library of Medicine. (2025). Mindfulness-Oriented Recovery Enhancement for Chronic Pain and Opioid Relapse (NCT04491968). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT04491968