Treating addiction with an addictive drug: the ketamine paradox revisited

By
Alqassem Y. Hakami
July 9, 2026
0 min

Frontiers In Psychiatry

Overview

This review evaluates ketamine's potential as a treatment for substance use disorders (SUDs) and treatment-resistant depression (TRD). It highlights reductions in cravings and abstinent days, while also addressing concerns regarding misuse and variability in clinical outcomes.

Background

Substance use disorders and treatment-resistant depression pose significant global health challenges, characterized by high relapse rates and limited treatment efficacy. Current pharmacological and behavioral interventions are often inadequate, necessitating the exploration of novel therapies like ketamine.

Data Highlights

Ketamine combined with psychotherapy has shown reductions in cravings and increases in abstinent days in small-to-moderate Phase 2 trials for alcohol and cocaine use disorders.

Key Findings

Ketamine promotes synaptic plasticity through NMDA receptor antagonism, potentially disrupting maladaptive reward-related memories.
Variability in dosing strategies and follow-up periods complicates the generalization of findings regarding ketamine's efficacy.
Acute adverse effects of ketamine are generally transient under clinical supervision.
There is a risk of misuse associated with ketamine, particularly in unsupervised settings.
Long-term safety data and larger-scale trials are needed to define ketamine's role in psychiatric and addiction treatment frameworks.