Neurobiological Mechanisms of Ketamine Use, its Addiction, and Withdrawal: A Mini Review.
Current reviews in clinical and experimental pharmacology – March 03, 2025
Source: PubMed
Summary
Ketamine's dual nature as both a promising depression treatment and a potential source of addiction lies in its complex effects on brain chemistry. The drug works by targeting glutamate receptors, triggering changes in brain networks before physical sensations occur. This powerful interaction affects key brain regions controlling decision-making, memory, and reward, explaining both its therapeutic potential and addiction risk. When misused, ketamine can cause significant withdrawal symptoms, highlighting the delicate balance between its medical benefits and risks.
Abstract
Ketamine, a substance used for anesthesia and known for inducing dissociation, can lead to addiction and the development of severe withdrawal symptoms. Ketamine alters brain networks before affecting somesthetic sensation. Ketamine abuse was especially prevalent in East and Southeast Asia, and its popularity has continued to expand globally in recent decades. Ketamine is gaining popularity in the public and private sectors as a cheaper off-label depression treatment. Unfortunately, ketamine may cause side effects, such as heart and blood vessel instability, respiratory depression, liver injury, hallucinations, etc. The pain-relieving and mental effects of ketamine might induce reliance; thus, it should be used cautiously. This review highlights the neurobiological processes underpinnings of ketamine's addictive potential, withdrawal, and its effects on brain networks like the prefrontal cortex, hippocampus, and mesolimbic pathway, which play vital roles in decision-making, memory, and reward processing. In addition, the involvement of neurotransmitter systems, specifically glutamate and dopamine, in mediating the addictive properties of ketamine and the neuroadaptive changes that occurred during withdrawal are also discussed. It also explains that low-dose ketamine can alter the secretion of stress hormone cortisol and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, possibly attributed to the current repurposing study of ketamine as a fast-acting antidepressant. Understanding these pathways is essential for developing effective ketamine addiction treatments, managing withdrawal symptoms, and possibly reversing brain changes for the betterment of human health and psychological well- being.