Chronic Physical and Psychological Effects of Ketamine

Image: Ketamine powder.
Retrieved from Red Button on Feb. 6, 2013.

Ketamine-induced ulcerative cystitis

Ketamine-induced ulcerative cystitis is a recently identified condition which can have severe and potentially long-lasting impact on the individual. Shahani et al. [38] first documented cases in nine dependent ketamine users, describing symptoms such as frequency and urgency of urination, dysuria, urge incontinence and occasionally painful haematuria (blood in urine). CT scans of these individuals revealed a marked thickening of the bladder wall, a small bladder capacity and perivesicular standing consistent with severe inflammation. At cystoscopy all patients had severe ulcerative cystitits. Biopsies in four of these cases found denuded urothelial mucosa with thin layers of reactive and regenerating epithelial cells and ulcerations with vascular granulation tissue and scattered inflammatory cells. Cessation of ketamine use provided some relief of symptoms...

Kidney dysfunction

Another emergent physical health problem associated with frequent, high-dose ketamine use appears to be hydronephrosis (water on the kidney) secondary to urinary tract problems. In their study of ketamine-induced ulcerative cystitis, Chu et al. [42] reported that 30 (51%) of patients presented with either unilateral (7%) or bilateral (44%) hydronephrosis (water on the kidney). On this initial assessment four patients also showed papillary necrosis (destruction of kidney cells, and this led to renal failure in one, who had complete obstruction of the urethra.

'K-cramps'

A third of 90 ketamine users in one study spontaneously reported 'K-cramps'- intense abdominal pain- as a result of prolonged, heavy ketamine use [35]. Frequent ketamine users often report taking more ketamine to alleviate this pain and this can make attempts to quit using fail. The aetiology of K-cramps remains unclear, but three small case studies (one, three and two patients, respectively) have reported the existence of 'colicky' upper gastric pain in young ketamine users, all of whom also presented with abnormal liver function. CT scans of these patients found dilation of the common bile duct with a smooth tapered end, mimicking choledochal cysts (congenital conditions associated with benign cystic dilatation of bile ducts). These symptoms abated when the patients stopped using ketamine.
A larger study of ER presentations [46] also reported that 21% of ketamine patients presented with abdominal pains and 15% with abnormal liver function, which concur with these reports of bilary problems.
Among ketamine users there is a belief that 'K-cramps'or 'K-belly' arises from swallowing the drips when ketamine is snorted intranasally... However, this... would seem to be incorrect based on evidence reviewed above.

Depression

Increased depression in both daily users and ex-ketamine users was found over the course of 1 year in our longitudial study but not in current infrequent (>1 per month, <3 times per week) users. However, this elevated depression was not a clinical levels and the increase was not correlated with changes in ketamine use.
In contrast, a preliminary study of seven patients suggested that one dose of ketamine can have rapid and relatively prolonged antidepressant effects in depressed patients who did not respond to usual treatments... [The] chronic effects of the drug should be monitored if repeated dosing is to be a strategy in the treatment of depression.

Psychosis

In healthy volunteers, one dose of ketamine induces transient positive and negative symptoms of schizophrenia. In schizophrenic patients who have been stabilized on antipsychotic medication, ketamine causes a resurgence of psychotic symptoms, which are remarkably similar to those each individual exhibited in the acute phase of their illness.

Cognitive impairment

The NMDA receptor is thought to underpin the form of synaptic plasticity known as long-term potentiation, which is central for learning and memory. Given that the principle action of ketamine is at this NMDA receptor, the consequences of ketamine use on cognition have been fairly widely investigated. In humans, a single dose of ketamine induces marked, dose-dependent impairments in working and episodic memory which would impact profoundly on users' ability to function [57]. In mice, impaired fear memory (decreasing fear in fear conditioning paradigm) has bee found after 4 but not 2 weeks of daily injection of 5mg/kg.
Several studies have examined cognitive function in infrequent and frequent ketamine users. Overall, infrequent or recreational ketamine use does not appear to be associated with long-term cognitive impairment. The most robust findings are that frequent ketamine users exhibit profound impairments in both short and long-term memory. Many studies have been cross-sectional and cannot address causation. However, in a longitudinal study, frequent ketamine use caused impairments in visual recognition and spatial working memory that correlated with changes in level of ketamine use over 12 months. Other impairments in planning and frontal functions have been observed, but appear so far to be unrelated to measures of ketamine use. Memory impairments may be reversible when individuals stop using the drug, as they were not found in a group of 30 ex-ketamine users who had been abstinent for at least a year. The cognitive consequences of repeated ketamine use in paediatric anaesthesia would also merit further investigation.

Neurological changes

Increased D1 receptor binding in the right dorsolateral prefrontal cortex of ketamine users has been reported, indicating upregulation of dopaminergic receptors. White matter abnormalities have been observed in ketamine addicts compared to controls. Reduced fractional anisotropy correlated with the degree of ketamine use in the bilateral frontal and left temporoparietal regions. However, similar changes have been observed in other drug-dependent populations, so these may not be specific effects of ketamine. There were also small changes in the temporal region that may relate to the drug's impairment of episodic memory.

Withdrawal symptoms following abstinence

There is conflicting evidence of the existence of a 'withdrawal syndrome' following cessation of ketamine use. Cravings seem to be a key problem in frequent users: 28 of the 30 daily users in a study by Morgan et al. reported having tried to stop taking the drug but failed; all reported ketamine cravings as the reason for failure. The same study found 12 of the 30 daily users reported withdrawal symptoms characterized by anxiety, shaking, sweating and palpitations when they stopped using. A few published case studies also show craving and somatic and psychological aspects of anxiety as withdrawal symptoms.

- excerpts from Ketamine use: a review by Celia J. A. Morgan & H. Valerie Currant on behalf of the Independent Scientific Committee on Drugs (ISCD). DOI: 10.11.11

ketamine, risks, addiction, kidney, urinary, overdose
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