New effects of ketamine abuse uncovered

Posted on 19 March 2016

Research conducted by York biologists and part-funded by C2D2 has revealed how recreational ketamine abuse damages the bladder.

The research was led by Dr Simon Baker in the University of York’s Department of Biology, in collaboration with clinicians from Middlesbrough and Leeds hospitals with support from C2D2. The team demonstrated how ketamine present in urine causes damage to the epithelial lining of the bladder, allowing urine to penetrate into underlying tissues which causes inflammation and extreme pain. In some cases this pain can be so extreme that patients need to have their bladder removed (cystectomy).

There were two linked studies; the first study sought to determine whether bladder damage was caused by direct contact with urinary ketamine or whether the drug causes a systemic change in the whole body that affects the organ.

To understand this the team studied epithelial cells lining the bladder and also in an adjacent remnant of the foetal urinary tract, no longer in contact with urine, known as an urachus.

They found that the epithelial cells lining the bladder were almost completely stripped away whereas the epithelial cells from the urachus appeared healthy. This allowed them to conclude that direct contact with urine is critical to the toxicity of ketamine to the bladder epithelium rather than systemic factors.

In the second study, the researchers used epithelium cells taken from healthy patients to study how ketamine affects the bladder.

The researchers found that ketamine overwhelms the cell’s internal power stations, known as mitochondria, causing a catastrophic release of toxins. To avoid this “melt-down”, cells commit a controlled form of suicide (apoptosis) to limit the damage and attempt to protect the remaining tissue; however, in the case of prolonged ketamine abuse, eventually all the epithelial cells are killed.

Dr Baker, Senior Postdoctoral Research Fellow in York’s Jack Birch Unit for Molecular Carcinogenesis, said: “These two studies combine to demonstrate that direct contact with urinary ketamine causes significant bladder damage, and shows how this drug causes the death of previously healthy bladder cells.

“We now have a more detailed understanding of how and why chronic ketamine abuse results in bladder problems and cystitis. Understanding the full side-effects of ketamine is very important as other researchers are currently investigating the potential for this drug to spawn a new generation of anti-depressants.”

Notes to editors:

The paper ‘A Rare Urachal Cyst in a Case of Ketamine-induced Cystitis Provides Mechanistic Insights’ is published in Urology Journal. To read, visit: http://www.ncbi.nlm.nih.gov/pubmed/26743387
The paper ‘Ketamine-induced apoptosis in normal human urothelial cells: a direct, N-methyl-D-aspartate receptor-independent pathway characterised by mitochondrial stress’ is published in The American Journal of Pathology. To read, visit: http://www.sciencedirect.com/science/article/pii/S0002944016000730
The group also has two additional previous publications on ketamine cystitis: A 2013 study showing that ketamine abuse affects the nerves of the bladder potentially contributing to the pain experienced: http://www.ncbi.nlm.nih.gov/pubmed/24252413 and a 2011 review of the existing research literature at the time: http://www.ncbi.nlm.nih.gov/pubmed/21314885
Original University press release

New effects of ketamine abuse uncovered

Notes to editors:

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