Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans

Summary & key facts

Researchers gave 19 healthy people two low doses of ketamine or a placebo through an IV to see how the drug affects behavior, thinking, and body chemistry. The higher dose caused temporary changes that looked like some symptoms of schizophrenia and dissociation, made attention and certain thinking skills worse, and raised stress hormones and blood pressure. Overall, the study shows that even subanesthetic amounts of ketamine can cause short-term changes in perception, memory, thinking, and some body systems.

Key facts:

• Nineteen healthy volunteers took part in a carefully controlled study where each person had three test days and received either a placebo, a low ketamine dose, or a higher ketamine dose through a 40-minute IV.
• The two ketamine doses were 0.1 milligrams per kilogram and 0.5 milligrams per kilogram of body weight.
• On the higher dose, people showed behaviors similar to the positive and negative symptoms of schizophrenia, such as unusual thoughts and social withdrawal.
• Ketamine caused altered perception and symptoms like those seen in dissociative states, which can feel like being disconnected from yourself or the world.
• Ketamine made people perform worse on tests of vigilance, verbal fluency, and a test that measures flexible thinking and planning.
• Memory was affected in a specific way: delayed word recall was worse, while immediate recall and recall after a distraction were not clearly harmed.
• The drug raised the stress hormone cortisol and the hormone prolactin in a dose-dependent way, meaning the higher dose caused bigger increases.
• Ketamine caused small increases in blood pressure.
• Ketamine did not change scores on a basic global mental-status test at the doses used, and it did not change one measured breakdown product of noradrenaline while it reduced the normal day-long drop in a dopamine-related chemical at the higher dose.

Abstract

BACKGROUND: To characterize further behavioral, cognitive, neuroendocrine, and physiological effects of subanesthetic doses of ketamine hydrochloride in healthy human subjects. Ketamine, a phencyclidine hydrochloride derivative, is a dissociative anesthetic and a noncompetitive antagonist of the N-methyl-D-aspartate subtype of excitatory amino acid receptor. METHODS: Nineteen healthy subjects recruited by advertisements from the community participated in this randomized, double-blind, placebo-controlled study. Subjects completed three test days involving the 40-minute intravenous administration of placebo, ketamine hydrochloride (0.1 mg/kg), or ketamine hydrochloride (0.5 mg/kg). Behaviors associated with the positive and negative symptoms of schizophrenia were assessed by using the Brief Psychiatric Rating Scale. Changes in perception and behaviors associated with dissociative states were assessed by the Perceptual Aberration Subscale of the Wisconsin Psychosis Proneness Scale and the Clinician-Administered Dissociative States Scale. Cognitive function was assessed by using the (1) Mini-Mental State Examination; (2) tests sensitive to frontal cortical dysfunction, including a continuous performance vigilance task, a verbal fluency task, and the Wisconsin Card Sorting Test; and (3) tests of immediate and delayed recall. Plasma levels of cortisol, prolactin, homovanillic acid, and 3-methoxy-4-hydroxyphenethyleneglycol were measured. RESULTS: Ketamine (1) produced behaviors similar to the positive and negative symptoms of schizophrenia; (2) elicited alterations in perception; (3) impaired performance on tests of vigilance, verbal fluency, and the Wisconsin Card Sorting Test; (4) evoked symptoms similar to dissociative states; and (5) preferentially disrupted delayed word recall, sparing immediate recall and postdistraction recall. Ketamine had no significant effect on the Mini-Mental State Examination at the doses studied. Ketamine also had no effect on plasma 3-methoxy-4-hydroxyphenethyleneglycol levels, although it blunted a test day decline in plasma homovanillic acid levels at the higher dose. It also dose dependently increased plasma cortisol and prolactin levels. Ketamine produced small dose-dependent increases in blood pressure. CONCLUSIONS: These data indicate that N-methyl-D-aspartate antagonists produce a broad range of symptoms, behaviors, and cognitive deficits that resemble aspects of endogenous psychoses, particularly schizophrenia and dissociative states.

Topics

Nicotinic Acetylcholine Receptors Study Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Anesthesia Audiology Cognition Dissociative Internal medicine Ketamine Medicine Neuropsychology Neuroscience NMDA receptor Phencyclidine Positive and Negative Syndrome Scale Psychiatry Psychology Psychosis Receptor Verbal fluency test Vigilance (psychology) Wisconsin Card Sorting Test

Substances

Ketamine

Conditions & symptoms

Difficulty focusing Feeling disconnected from others