Twelve healthy men recruited from among physicians and medical students residing in the Hannover (Germany) area received placebo, 0.03 and 0.05 mg/min/kg S-(+)-ketamine in a randomized, double blind study of the acute effects of S-(+)-ketamine on consciousness and binocular visual perception. Each participant was enrolled in three sessions; placebo, low dose (0.03 mg/min/kg) and high-dose (0.05 mg/min/kg) ketamine. Self-reported alterations in consciousness were assessed via the OAVAV, a revised version of the Altered States of Consciousness (APS or ASC) measure. This scale assesses positive and negative derealization, alterations in thought and perception, and changes in alertness and clarity of thought. An observer-scored measure of psychiatric signs (Brief Psychiatric Rating Scale, or BPRS) assessed anxious or depressed mood, hostility and suspiciousness, activation, anergia (lack of energy or movement), and thought disorders (such as delusional thoughts). Participants viewed stereoscopic images (images taken from different angles, intended to represent binocular view) of familiar and less familiar objects, either presented as expected, or with left and right images exchanged so as to create an effect of reverse, or inverted, depth (that is, concavity in a convex image and vise versa). The researchers told participants that some images would be inverted while others would not be. Participants viewed target images and distractors (images lacking depth cues or without a matching inverted image). Previous studies have found that this illusion is attenuated in people with schizophrenia, as well as after sleep deprivation, ethanol or cannabis intoxication, and ethanol withdrawal in individuals without schizophrenia. Placebo and ketamine were administered via continuous intravenous infusion. Scores on outcome measures (BPRS, OAVAV and binocular depth illusion) were compared across conditions.

Low-dose S-(+)-ketamine only increased BPRS anergia and OAVAV vigilance reduction scores. High dose S-(+)-ketamine increased BPRS anergia, anxiety/depression, thought disorder, activation and hostility/suspiciousness scores, and all OAVAV scores, including a further increase in vigilance reduction. However, high-dose S- (+)-ketamine did not alter observable behavior as profoundly as it did perception, mood and thought. Contrary to expectation, neither low nor high-dose S-(+)-ketamine altered strength of depth illusions, either of familiar or less familiar images. S-(+)-ketamine produced some effects seen in psychosis, such as altered perception and thought, anxiety, anergia and hostility and suspiciousness. However, some S-(+)-ketamine effects differ from those seen in psychosis, including large increases in reduced vigilance, even after low doses, and failure to attenuate the inverted depth perception illusion. The authors hypothesize that the top-down “corrective” processes responsible for the inverted depth illusion are unaffected by S-(+)-ketamine. Given that binocular depth perception illusions are attenuated under conditions that bear little in common with psychosis (sleep deprivation, cannabis and ethanol intoxication) and given that the illusion is not attenuated under ketamine intoxication, a condition sharing similarities with psychosis, attenuation of the inverted depth perception illusion may serve as a marker of schizophrenia that is independent of psychosis. Effects seen in this study may not generalize to racemic ketamine, as there is evidence that R-(-)-ketamine and S-(+)-ketamine differ in their actions on specific receptors and produce different changes in brain activity (Vollenweider et al. 1997.) Study limitations also include exclusion of female participants, though at present there is no reason to expect the existence of gender differences in response to ketamine.

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