Absence of behavioral sensitization in healthy human subjects following repeated exposure to ketamine

Cho, Hyun Sang; D’Souza, Deepak Cyril; Gueorguieva, Ralitza; Perry, Edward; Madonick, Steven; Karper, Laurence P.; Abi‐Dargham, Anissa; Belger, Ayşenil; Abi-Saab, Walid; Lipschitz, Deborah S.; Bennet, Alexandre; Seibyl, John; Krystal, John H.

doi:10.1007/s00213-004-2066-5

Cited by 33 publications

(25 citation statements)

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“…In our longer-term follow-up data, we found no evidence of ketamine abuse by subjects following study participation and no evidence of subsequent psychiatric problems related to ketamine exposure (alone or in combination with other study drugs). A recent analysis of this data failed to find evidence of sensitization to the effects of ketamine in those subjects who had more than one exposure to this drug (Cho et al 2005). These findings are consistent with the lack of long-term effects reported with anesthetic doses of ketamine (Corssen et al 1971;Moretti et al 1984) and further document the safety of subanesthetic doses of ketamine as a psychopharmacologic probe in healthy subjects.…”

Section: Discussionsupporting

confidence: 78%

Psychiatric safety of ketamine in psychopharmacology research

et al. 2007

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Section: Discussionsupporting

confidence: 78%

Psychiatric safety of ketamine in psychopharmacology research

et al. 2007

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“…Moreover, a placebocontrolled, randomized, double-blind psychopharmacological trial found that intravenous ketamine (0.23 and 0.5 mg/kg) impaired performance on tasks that tested executive function in humans [45]. There is no evidence that repeated ketamine exposure increases psychotic, perceptual, euphoric, or anxiogenic responses [46]. Ketamine administration at sub-anesthetic doses has been consistently shown to present an acceptable level of risk in healthy individuals throughout their participation in a study [47].…”

Section: Cognitive Effects Of Ketaminementioning

confidence: 99%

Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

et al. 2016

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Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Conventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hindered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive Nmethyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fastacting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concern. In this review, we focus on the limitations of ketamine, including neurotoxicity, cognitive dysfunction, adverse events associated with mental status, psychotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine (esketamine) and R-ketamine, are also discussed. R-ketamine has greater antidepressant actions than S-ketamine, without ketamine-related sideeffects. Future treatment strategies should consider using Rketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term ketamine use.

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“…Subjects were informed about the potential for psychosis, anxiety, and panic. Individuals at risk for psychosis were excluded from participating in these studies after undergoing a rigorous screening process described elsewhere (e.g., Krystal et al 2005a,b;Cho et al 2005). Subjects received ketamine hydrochloride or placebo (Ketalar, Parke-Davis, Kalamazoo, MI, USA) by intravenous route in a randomized, counterbalanced order under double-blind, placebo-controlled conditions.…”

Section: Data Sourcesmentioning

confidence: 99%

“…Many factors may play a role in determining the response to ketamine, some of which have only recently begun to be investigated, including family history of alcohol abuse (Petrakis et al 2004), previous exposure to ketamine (Cho et al 2005), and genetic variation in the apolipoprotein E epsilon 4 allele . Other important factors have not been investigated adequately so far due to small sample sizes.…”

Section: Introductionmentioning

confidence: 99%