Ketamine bladder

Ketamine is a popular recreational drug in many countries; its popularity stemming in part from its low cost, and in part from its reputation for having a low addicition risk and few side-effects (and because of its interesting psychadelic effects, of course). However, it is becoming increasingly clear that at least the latter of these suppositions is not entirely accurate.

Some years ago, doctors in several countries started to notice that otherwise healthy people were presenting with damaged bladders and urinary tracts. Such urinary system damage has now been described over a hundred times in the literature [1]. In some cases the damage has been so severe that it has necessitated the complete removal of the damaged organs.

Within the ketamine-using community in the UK, the cause of such ‘ketamine bladder’ is often attributed to the drug crystallising in the bladder and causing damage. This explanation is understandable in the context of kidney stones – a condition that most people are aware of – but is not correct.

When a sufferer’s bladder is investigated, its wall is generally seen to have become thicker, markedly reducing the capacity of the bladder. This leads to some of the symptoms of ‘ketamine bladder’, such as the need to urinate often and pain when the bladder fills. Indeed, due to this pain some patients are not able to fill their bladder sufficiently for some relevant medical tests to be carried out. In addition to this change in the bladder wall, the mucosal layer of the bladder is enlarged, an indicator of long-term inflammatory change [2].

Indicators of inflammation have also been observed in mice that have been exposed to ketamine for several months. In such mice, special cells known as monocytes can be found within the kidney and in the wall of the bladder [3]. The role of these cells in the body is to move to areas of infection and inflammation, where they will then form part of the body’s immune response.

What, though, is prompting this immune response? It is extremely unlikely that the response is to ketamine itself, and so we must look a little deeper in order to find a cause.

In addition to its effects in the brain, ketamine has peripheral effects on particular neurotransmitters that are found in smooth muscle, called adrenoceptors [4]. As the bladder and urethra are formed in a large part by smooth muscle, this effect is likely to be highly relevant in these regions; a supposition potentially borne out by the observation that ketamine reduces the amount that rat bladder smooth muscle contracts [5], and the observation that mice exposed to ketamine have alterations to the innervations of the muscle in their bladders [3].

With these changes to the functioning of the muscles in the urinary system, it is possible that the muscle cells themselves are becoming damaged over time. Such damage may release cell components into the tissues, in turn prompting the body to mount an inflammatory response. It may be this inflammatory response in conjunction with the changes in muscle function that are causing ‘ketamine bladder’, although this remains a personal speculation at present.

Unfortunately there is no single treatment for the condition at present. The most important factor is a cessation of ketamine use, which can then be coupled with a variety of management strategies on a case-by-case basis. 


References


1. Middela S, & Pearce I (2011). Ketamine-induced vesicopathy: a literature review. International journal of clinical practice, 65 (1), 27-30 PMID: 21155941


2. Mason K, Cottrell AM, Corrigan AG, Gillatt DA, & Mitchelmore AE (2010). Ketamine-associated lower urinary tract destruction: a new radiological challenge. Clinical radiology, 65 (10), 795-800 PMID: 20797465


3. Yeung, L., Rudd, J., Lam, W., Mak, Y., & Yew, D. (2009). Mice are prone to kidney pathology after prolonged ketamine addiction Toxicology Letters, 191 (2-3), 275-278 DOI: 10.1016/j.toxlet.2009.09.006


4. Bevan RK, Rose MA, & Duggan KA (1997). Evidence for direct interaction of ketamine with alpha 1- and beta 2-adrenoceptors. Clinical and experimental pharmacology & physiology, 24 (12), 923-6 PMID: 9406657  


5. Ceran C, Pampal A, Goktas O, Pampal HK, & Olmez E (2010). Commonly used intravenous anesthetics decrease bladder contractility: An in vitro study of the effects of propofol, ketamine, and midazolam on the rat bladder. Indian journal of urology : IJU : journal of the Urological Society of India, 26 (3), 364-8 PMID: 21116355