For years, the most recognized physical risk of chronic ketamine abuse has been bladder damage, but a new clinical puzzle is emerging: severe injury to the liver and bile ducts, known as Ketamine-induced Sclerosing Cholangitis (K-SC). This episode dives into a recent case series detailing patients—including older and female European users—broadening the picture of who is at risk. Sclerosing cholangitis is a progressive condition where chronic inflammation leads to severe scarring and narrowing of the bile ducts. This obstruction causes bile backup (cholestasis), which, if unchecked, can result in irreversible cirrhosis—often making a liver transplant the only option. We explain why laboratory markers like GGT and ALP are critical red flags for this damage. How does this anesthetic target the liver's plumbing? The leading hypothesis suggests chronic, high-dose exposure over time causes sustained spasms due to ketamine's effect on NMDA receptors located in the bile duct smooth muscle. Crucially, the severity of this liver damage often tracks directly with the severity of a patient's urinary symptoms, suggesting a systemic toxic effect on similar smooth muscle tissues in both the bladder and the biliary system. Using diagnostic criteria, physicians confirmed K-SC by ruling out other look-alike conditions (like PSC, which is tied to IBD). The strongest evidence linking the drug to the severe damage was the dramatic clinical improvement in lab results immediately after patients ceased ketamine use. The main takeaway for anyone concerned is non-negotiable: the absolute first line of defense is immediate and permanent cessation of all ketamine use. Management requires a comprehensive multidisciplinary team—gastroenterologists, urologists, and addiction specialists—to manage the devastating progression and provide essential addiction support. This exploration underscores a tragic potential consequence of long-term abuse and the urgent need for more longitudinal research. Source Research Paper: Vanrusselt, A., Nijs, J., Van den Bergh, L., Schoofs, N., Smets, S., Strybol, D., & Rappaport, A. (2025). Ketamine-induced sclerosing cholangitis: a case series. Acta Gastro-Enterologica Belgica, 88(3), 271–276. https://doi.org/10.51821/88.3.13914