Superstitious conditioning as a model of delusion formation following chronic but not acute ketamine in humans

Background Ketamine has previously been shown to induce delusion-like or referential beliefs, both acutely in healthy volunteers and naturalistically among nonintoxicated users of the drug. Delusions are theoretically underpinned by increased superstitious conditioning or the erroneous reinforcement of random events. Materials and methods Using a novel and objectively measured superstitious conditioning task, experiment 1 assessed healthy volunteers before and during placebo ( n = 16), low-dose ( n = 15), and high-dose ketamine ( n = 16) under randomized and double-blind conditions. Experiment 2 used the same task to compare ketamine users ( n = 18), polydrug controls ( n = 19), and nondrug-using controls ( n = 17). Results In experiment 1, ketamine produced dose-dependent psychotomimetic effects but did not cause changes in superstitious conditioning. Experiment 2 found increased levels of superstitious conditioning among ketamine users compared to polydrug and nondrug-using controls, respectively, as evidenced by both objective task responses and subjective beliefs following the task. Conclusions Results indicate that chronic but not acute exposure to ketamine may increase the propensity to adopt superstitious conditioning. These findings are discussed in terms of acute and chronic ketamine models of delusion-like belief formation in schizophrenia.