Substance use disorders rank among the fastest-growing health-related issues worldwide, affecting millions. The rate of intake doesn't appear to be slowing despite the rapid growth of evidence-based treatments—behavioral and pharmacological interventions. However, a systematic review published recently in Frontiers in Psychiatry reveals that ketamine, widely known for its wide-spectrum anesthetic properties, may offer new hope in the treatment of SUDs.

Medical University of South Carolina researchers, along with the Ralph H. Johnson VA Medical Center, studied ketamine for treating a selection of substance use disorders. Here's what they found:

The Glutamate Link

These authors point to the role of glutamatergic dysregulation in addiction pathology. Ketamine, being a potent antagonist of the NMDA glutamatergic receptor, may contribute to the correction of this neurochemical imbalance.

Promising results have emerged in several SUDs.

The review identified seven completed studies related to alcohol, cocaine, and opioid use disorders:

• Alcohol Use Disorder: Of the two studies that reported improved abstinence on the part of participants receiving ketamine, effect sizes remained significant for as long as two years after a single infusion.

• Cocaine Use Disorder: Improvements in craving, motivation, and reduction in the rates of cocaine use have been reported by two studies. Their small sample sizes and short follow-up periods raised a limitation to these studies simultaneously.

• Opioid Use Disorder: Three demonstrated improvements in abstinence rates for the ketamine group compared to control groups.

Limitations and Further Directions

While these results are encouraging, the authors point out several limitations in the thus far conducted studies:

• Small sample sizes within some of the studies

• Lack of placebo-controlled trials in some instances

• Short follow-up periods in certain studies

The review also identified six active clinical trials related to the use of ketamine for treating disorders caused by the use of alcohol, cocaine, cannabis, and opioids. These might provide a far better evidence base for ketamine's potential in SUD treatment.

Possible Mechanism of Action

The authors also refer to the fact that the rapid antidepressant actions of ketamine, presumably a result of improved prefrontal cortex glutamate homeostasis, serve to support further the efficacy of ketamine in the treatment of SUDs. Moreover, ketamine is reported to enhance synaptic plasticity so that the patient learns new behaviors and can break addictive patterns.

While more research is needed, this systematic review puts into light a promising treatment option for various substance use disorders by ketamine. Because it can address glutamatergic dysregulation and may promote neuroplasticity, a new avenue for the treatment of addiction may be opened. There is little question that, while final results of clinical trials underway are awaited, ketamine represents one of the most exciting areas of research in addiction medicine at this time. Further studies confirming these preliminary findings could result in ketamine becoming an important intervention to help individuals surmount the challenges of substance use disorders and achieve long-term recovery.