The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use

Emergency Department, Guy's and St Thomas' NHS Foundation Trust, London, UK
Emerging Health Threats Journal 04/2011; 4(1):7107. DOI: 10.3402/ehtj.v4i0.7107
Source: PubMed


Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine.
The predominant features of acute toxicity associated with the recreational use of ketamine are neuro-behavioural abnormalities such as agitation, hallucinations, anxiety, and psychosis. Secondary to these, individuals put themselves at greater risk of physical harm/trauma. Cardiovascular features (hypertension and tachycardia) occur less frequently and the risk of death from recreational use is low and is predominately due to the physical harm/trauma.
Long-term recreational use of ketamine can be associated with the development of psychological dependence and tolerance. There are reports of gastro-intestinal toxicity, particularly abdominal pain and abnormal liver function tests, and of neuropsychiatric disorders, typically a schizophrenia-like syndrome, in long-term users. Finally, there are increasing reports of urological disorders, particularly haemorrhagic cystitis, associated with long-term use. The management of these problems associated with the long-term use of ketamine is largely supportive and abstinence from ongoing exposure to ketamine.
In this review we will collate the available information on the epidemiology of recreational use of ketamine and describe the patterns of acute and chronic toxicity associated with its recreational use and the management of this toxicity.

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    • "Rapid tolerance to ketamine's characteristic acute psychoactive effects is well recognized and considered to be involved in the development of addictive behavior in recreational ketamine users (Jansen and Darracot-Cankovic 2001; Wolff and Winstock 2006; Kalsi, Wood, and Dargan 2011; Morgan and Curran 2012; Bokor and Anderson 2014). Trials of repeated or serial ketamine infusions did not describe any tolerance in ketamine's antidepressant response (Murrough et al. 2013; Rasmussen et al. 2013; Shiroma et al. 2014). "
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    ABSTRACT: Sub-anaesthetic ketamine is of special interest for depression research due to its rapid and potent but short-lived antidepressant response (after-effect). The presented case is the first one in the literature which deals in detail with the transfer from ketamine's antidepressant action to ketamine addiction. A 50-year-old anaesthetic nurse, who had never been treated with antidepressants before, started with self-injecting ketamine racemate 50 mg IM once a week to cope with her major depression. She continuously stole ketamine from hospital stocks. Due to a gradually developing tolerance to ketamine's antidepressant action, she stepwise increased dose and frequency of ketamine self-injections up to daily 2 g IM (three-fold her anaesthetic dose) over six months. This was accompanied by the development of ketamine addiction, loss of consciousness, dissociative immobility, and amnesia. Inpatient detoxification treatment was characterized by a strong craving for ketamine and, later on, by the occurrence of a severe depressive episode remitting on venlafaxine. A 14-week follow-up documented a normal condition without any ketamine sequelae, such as craving, psychosis, depression, or cognitive abnormalities. Thus, awareness of ketamine addiction potential, even in patients who received ketamine for antidepressant purposes, is important.
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    ABSTRACT: Long-term regular use of ketamine has been reported to be associated with severe symptomatic urinary tract problems. Methoxetamine, an arylcyclohexylamine derivative of ketamine, is marketed as a "bladder safe" derivative of ketamine, and no cases of acute toxicity following analytically confirmed methoxetamine use have been reported to date. We report here a case series of three individuals with acute toxicity related to the analytically confirmed use of methoxetamine. Three patients aged between 28 and 42 years presented to the Emergency Department (ED) on unrelated occasions having used methoxetamine. Clinical features were suggestive of a "dissociative/catatonic" state similar to that seen with ketamine; in addition, they had clinical features of acute sympathomimetic toxicity with significant tachycardia and hypertension. All were managed with low-dose benzodiazepines and discharged home once their symptoms/signs had settled. TOXICOLOGICAL SCREENING: Serum collected at the time of presentation to the ED was analysed qualitatively and quantitatively by gas chromatography-mass spectrometry. Serum concentrations ranged from 0.09 to 0.2 mg/L; in addition, detectable levels of 6-APB/5-APB were found in one of the patients. These three analytically confirmed cases demonstrate that acute methoxetamine-related toxicity is associated with both "dissociative" and "sympathomimetic" clinical features. The information from these three cases is useful to clinical pharmacologists, not only in managing individuals with acute methoxetamine toxicity but also in advising the appropriate legislative authorities on the risk of acute harm related to methoxetamine use. Further work is needed to determine whether methoxetamine is more "bladder friendly" than ketamine, as has been suggested by those marketing methoxetamine.
    European Journal of Clinical Pharmacology 12/2011; 68(5):853-6. DOI:10.1007/s00228-011-1199-9 · 2.97 Impact Factor
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    Affiliation: Projeto Diretrizes | Associação Médica Brasileira (AMB)
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