Psychotomimetic effects ketamine

Finally, there was a resurgence of interest in psychotogenic effects of ketamine in the early 1990s, following demonstrations that dissociative anesthetics such as PCP and ketamine induce their unique psychotomimetic effects by binding to a site located within the ion pore of the NMDA receptor (Anis et al., 1983 Javitt et al., 1987 Javitt and Zukin, 1991). Such studies remain ongoing and provide... 

One of the most popular hypotheses to explain schizophrenia, the glutamate hypothesis of schizophrenia, is based on the observation of psychotomimetic effects of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP), dizocilpine (MK-801), and ketamine. Like amphetamine, NMDA antagonists produce a psychosis-like state when administered to healthy individuals. Further... 

The pharmacological effects of the R- and 5-enantiomers of ketamine have been compared in 11 subjects who received //-ketamine 0.5 mg and then 5-ketamine 0.15 mg, separated by 1 week (432). Before and after each drug administration they were subjected to a painful stimulus using a nerve stimulator applied to the right central incisor tooth. Pain suppression was equal with the two drugs. The subjects reported more unpleasant psychotomimetic effects with 5-ketamine and more pleasant effects with //-ketamine. Seven of eleven subjects preferred //-ketamine, while none preferred 5-ketamine. These results suggest that the neuropsychiatric effect of ketamine may be predominantly due to the 5-enantiomer, and that //-ketamine may be a better alternative. This study is in direct distinction to earlier work suggesting that //-ketamine is responsible for most of the undesirable neuropsychiatric side effects of ketamine. 

Subanesthetic low-dose ketamine is thought to cause delirium and disturbing dreaming. A systematic review of NMDA receptor antagonists in preventive analgesia has shown that only one of 20 studies documented adverse psychotomimetic effects attributable to ketamine (435). In that study, ketamine was given by the epidural route in a relatively high dose. 

Prior use of benzodiazepines or opiates limits the psychotomimetic effects of ketamine. There has been a double-blind, placebo-controlled study of the role of lorazepam in reducing these effects after subanesthetic doses of ketamine in 23 volunteers who received lorazepam 2 mg or placebo, 2 hours before either a bolus dose of ketamine 0.26 mg/kg followed by an infusion of 0.65 mg/kg/hour or a placebo infusion (438). The ability of lorazepam to block the undesirable effects of ketamine was limited to just some effects. It reduced the ketamine-associated emotional distress and perceptual alterations, but exacerbated the sedative, attention-impairing, and amnesic effects of ketamine. However, it failed to reduce many of the cognitive and behavioral effects of ketamine. There were no pharmacokinetic interactions between subanesthetic doses of ketamine and lorazepam. 

Known as special K, jet, green, and other names on the street, ketamine is sometimes injected, but can be evaporated to solid crystals, powdered, and smoked, snorted, or swallowed. Marijuana cigarettes are sometimes soaked in the ketamine solution, allowed to dry, and then smoked. Ketamine has become popular as a rave club drug. Side effects include signiflcant transient increases in blood pressure and heart rate, respiratory depression, airway obstruction, apnea, muscular hypertonia, psychomotor and psychotomimetic effects, and acute dystonic reactions. Following overdose, seizures, polyneuropathy, increased intracranial pressure, respiratory arrest, and cardiac arrest may occur. 

Ketamine has also been studied as an adjuvant to lidocaine intravenous regional anesthesia for hand surgery in 40 patients who received ketamine 0.1 mg/kg either as an adjuvant to the lidocaine or as an intravenous injection [26 ]. There were no significant differences in tourniquet pain or opiate requirements, either intraoperatively or during the recovery period. There were no difference in the incidence of psychotomimetic effects and satisfaction was high in both groups. The authors felt that it would be unethical to include a control group, as ketamine has already been shown to be superior to placebo. However, this makes the conclusions hard to interpret. 

Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, et al. 1994. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 51 199-214. 

Oral ketamine is an effective analgesic in patients with chronic pain. In 21 patients with central and peripheral chronic neuropathic pain treated with oral ketamine, the starting dose was ketamine 100 mg/day, titrated upward by 40 mg/day increments every 2 days until a satisfactory effect was achieved, or until adverse effects became limiting (19). Nine patients discontinued ketamine because of intolerable adverse effects, including psychotomimetic symptoms, such as elevator effect or dissociative feelings, somnolence or insomnia, and sensory changes such as taste disturbance and somatic sensations. 

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