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New Research Shows How Ketamine Abuse Causes Bladder Damage

Baker SC, Shabir S, Georgopoulos NT, Southgate J. Ketamine-Induced Apoptosis in Normal Human Urothelial Cells: A Direct, N-Methyl-d-Aspartate Receptor-Independent Pathway Characterized by Mitochondrial Stress. Am J Pathol. 2016 Mar 16. pii: S0002-9440(16)00073-0. doi: 10.1016/j.ajpath.2015.12.014. [Epub ahead of print]
Recent studies have provided new insights into a form of bladder pain syndrome that has emerged due to recreational abuse of ketamine, an anesthetic that has hallucinogenic side effects. The disorder, known as ketamine-induced cystitis, is associated with ulceration of the bladder lining and chronic inflammation. One group of investigators sought to determine the direct effects of ketamine on the bladder lining by exposing urothelial cells to the drug. They found certain concentrations of the drug were toxic to the cells, causing damage to the urinary barrier. The research, detailed in the article, suggests that ketamine activates a pathway that leads to apoptosis, or programmed cell death; this finding provides the first evidence of a mechanism of direct toxicity of ketamine in the bladder. A related case report from the same research group provides additional insights on how ketamine abuse might lead to damage of the bladder lining. In this report, a patient with ketamine-induced cystitis developed a rare type of cyst and a nearly complete loss of bladder lining in regions that had contact with urine; this suggests that some factor in urine (rather than something affecting the whole body) is responsible for the ulceration–most likely ketamine itself or its metabolites. The finding underscores the importance of complete ketamine cessation in individuals who develop this form of cystitis.