Ketamine-Induced Hallucinations

Powers, Albert R. III
Gancsos, Mark G.
Finn, Emily S.
Morgan, Peter T.
Corlett, Philip R.

^aDepartment of Psychiatry, Yale School of Medicine, ^bInterdepartmental Neuroscience Program, Yale University, and ^cConnecticut Mental Health Center, New Haven, Conn., USA

^*Philip R. Corlett, PhD, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park St., New Haven, CT 06511 (USA), E-Mail [email protected]

Received March 20, 2015; Accepted July 11, 2015; previously published online September 12, 2015

Psychopathology 48(6):p 376-385, December 2015. | DOI: 10.1159/000438675

Abstract

Background:

Ketamine, the NMDA glutamate receptor antagonist drug, is increasingly employed as an experimental model of psychosis in healthy volunteers. At subanesthetic doses, it safely and reversibly causes delusion-like ideas, amotivation and perceptual disruptions reminiscent of the aberrant salience experiences that characterize first-episode psychosis. However, auditory verbal hallucinations, a hallmark symptom of schizophrenia, have not been reported consistently in healthy volunteers even at high doses of ketamine.

Sampling and Methods:

Here we present data from a set of healthy participants who received moderately dosed, placebo-controlled ketamine infusions in the reduced stimulation environment of the magnetic resonance imaging (MRI) scanner. We highlight the phenomenological experiences of 3 participants who experienced particularly vivid hallucinations.

Results:

Participants in this series reported auditory verbal and musical hallucinations at a ketamine dose that does not induce auditory hallucination outside of the scanner.

Conclusions:

We interpret the observation of ketamine-induced auditory verbal hallucinations in the context of the reduced perceptual environment of the MRI scanner and offer an explanation grounded in predictive coding models of perception and psychosis - the brain fills in expected perceptual inputs, and it does so more in situations of altered perceptual input. The altered perceptual input of the MRI scanner creates a mismatch between top-down perceptual expectations and the heightened bottom-up signals induced by ketamine. Such circumstances induce aberrant percepts, including musical and auditory verbal hallucinations. We suggest that these circumstances might represent a useful experimental model of auditory verbal hallucinations and highlight the impact of ambient sensory stimuli on psychopathology.