Treating addiction with an addictive drug: the ketamine paradox revisited - Summary - MDSpire

Treating addiction with an addictive drug: the ketamine paradox revisited

  • By

  • Alqassem Y. Hakami

  • July 9, 2026

  • 0 min

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Objective:

To critically evaluate ketamine’s therapeutic potential for substance use disorders (SUDs) while examining its neurobiological mechanisms, clinical efficacy, and risk of misuse.

Approach:
  • Review Methodology: A structured narrative review conducted in accordance with the SANRA framework using databases such as PubMed, Scopus, PsycINFO, and Web of Science, covering literature published until March 2026.
Key Findings:
  • Ketamine combined with psychotherapy has shown promising reductions in craving and increases in abstinent days in small-to-moderate Phase 2 trials for alcohol and cocaine use disorders.
  • Variability in dosing strategies, comparator conditions, and follow-up periods limits the generalizability of findings.
  • Effects on relapse prevention are inconsistent and less reliably positive.
  • Ketamine promotes synaptic plasticity via NMDA receptor antagonism and downstream glutamatergic signaling.
  • There is a well-established risk of misuse associated with ketamine, particularly in unsupervised or high-dose settings.
Interpretation:

Ketamine represents a promising but experimental intervention for refractory depression and selected SUDs, requiring careful patient selection and structured delivery.

Limitations:
  • Lack of larger-scale trials and long-term safety data.
  • Variability in study designs and methodologies across the literature.
Conclusion:

Ketamine may redefine treatment paradigms for TRD and addiction, but further research is essential to define its role within psychiatric and addiction treatment frameworks.

Original Source(s)

Treating addiction with an addictive drug: the ketamine paradox revisited

  • by Alqassem Y. Hakami

  • July 9, 2026

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