Though ketamine’s potential to cause bladder damage has been known about for some time, the biological mechanisms by which it does so have remained poorly understood. According to the results of two new studies that appear in the American Journal of Pathology, the drug may cause the cells lining the bladder to initiate their own death, enabling urine to penetrate underlying tissues. This, in turn, results in an extremely painful and unpleasant condition known as cystitis.
Ketamine is currently a hot topic, with the UN considering proposals from health officials regarding whether or not the substance should be internationally banned. While many scientists point to the drug’s usefulness as an anesthetic and a potential anti-depressant, excessive abuse of ketamine is also known to produce a number of adverse health effects – as is the case, of course, with just about any medication when taken in an uncontrolled manner.
Ketamine-induced cystitis (KIC) was first reported among recreational drug users in 2007, although scientists have struggled to determine whether this is caused by overall systemic changes or by the localized consequences of contact between ketamine and bladder cells.
To investigate, researchers from the University of York examined the bladder of a 30-year-old man with an eight-year history of ketamine abuse. Over this period, the cells of the epithelial lining of his bladder had become extensively damaged, leading to an extreme case of cystitis and requiring the whole bladder to be removed.
Since ketamine is predominantly excreted in urine, the epithelial cells of the bladder tend to come into contact with the drug in those who regularly ingest it. However, researchers were not sure whether this direct contact provides the main cause of KIC, or whether the body-wide effects of ketamine are what trigger this damage to the bladder.
Coincidentally, the patient also had a cyst attached to his bladder, consisting of tissue originating from the fetal urinary tract, known as the urachus. Examining this cyst, the study authors found that the epithelial cells were intact, and had not been damaged by ketamine. As such, they conclude that epithelial bladder cells are destroyed by direct contact with urinary ketamine, rather than by the drug’s systemic effect.
Exactly how ketamine damages these cells is elucidated in the second study, during which the researchers examined the ways in which the drug affects epithelial cells in a petri dish. Results showed that exposure to high concentrations of ketamine led to an increase in calcium levels within these cells.
While the origin of this extra calcium is currently unknown, it was found to have some rather drastic effects, sending the mitochondria of these cells into overdrive. Mitochondria are organelles found within cells that generate chemical energy using a molecule called adenosine triphosphate (ATP). Once ATP stores become depleted, however, mitochondrial membranes start to break down, resulting in the release of certain toxins that have the potential to damage surrounding tissues.
To prevent this from occurring, these cells automatically self-destruct via a process known as apoptosis, or programmed cell death. In this way, exposure to ketamine causes the epithelial cells of the bladder to essentially commit suicide, potentially leading to extensive and irreversible damage and resulting in KIC.
Therefore, while ketamine is considered by many to have highly beneficial medicinal effects, it can also cause significant damage if taken in an uncontrolled manner, which is why it should always be used only in clinical settings and never abused.