Chronic ketamine use kills bladder cells

THERE is growing evidence that chronic use of the recreational drug ketamine is linked with severe bladder problems. The findings may also have implications for the drug’s use as an antidepressant.

Used safely as a medical anaesthetic and analgesic for decades, ketamine has also risen in popularity as a recreational drug. The first case of severe bladder problems linked with ketamine use was documented in 2007, but little is known about the extent or cause of the problem.

Now a group of surgeons and scientists have raised the alarm in a review calling for more investigation (BJU International, DOI: 10.1111/j.1464-410X.2010.10031.x). They highlight effects such as incontinence and bladder shrinkage, as well as damage to the kidneys and ureter in people using ketamine frequently.

“It has a major impact on users such that they can be incontinent or have enormous pain,” says Dan Wood, a consultant urologist at University College London Hospitals, who led the review. He has seen 20 chronic ketamine users with urinary problems in the last three years and had to remove four patients’ bladders.

The review suggests that heavy users are more likely to suffer symptoms, and about 20 per cent of people who have taken high doses of ketamine several times a week over months to years have experienced urinary tract problems.

“[Recreational use] is a growing problem in the UK, Australia and New Zealand, and it’s a huge problem in south-east Asia, especially in Hong Kong,” says Val Curran, a psychopharmacologist at University College London, who is leading a review of ketamine for the UK’s Independent Scientific Committee on Drugs.

Previously, it was thought that bladder problems might have been down to substances combined with the drug for street sale. In an as-yet-unpublished study, Simon Baker and Jennifer Southgate at the University of York, UK, added ketamine to human urothelium cells, which line the bladder. With increasing doses, the cells rapidly became cytostatic – they stopped growing – and then died with further increases.

Ketamine has recently shown promise in treating depression. In a study published this week, Lisa Monteggia and colleagues at the University of Texas Southwestern Medical Center in Dallas show that in mouse models of depression, ketamine promotes the rapid synthesis of a protein known to have antidepressant effects, called brain-derived neurotrophic factor (BDNF). They suggest that this may provide a therapeutic target for developing fast-acting antidepressants, especially important for people at risk of suicide (Nature, DOI: 10.1038/nature10130).

“We are excited that ketamine could be the basis for a whole new generation of drugs, but concerned that these might show similar side effects to ketamine,” says Baker. Understanding more about ketamine’s actions could support the development of antidepressants without these negative effects.

-new scientist