Archives of General Psychiatry
April 1, 2009
Sagnik Bhattacharyya, Paolo Fusar‐poli, Stefan Borgwardt et al.
250 citations
Delta9-tetrahydrocannabinol (THC), a psychoactive constituent of cannabis, increased psychotic symptoms, anxiety, intoxication, and sedation in healthy men with minimal prior cannabis use, while cannabidiol had no significant effect on these measures. Verbal learning performance was not significantly affected by either drug. THC altered brain activation in the parahippocampal gyrus during encoding and in the ventrostriatum during retrieval, with the ventrostriatal change directly correlating with induced psychotic symptoms. These findings suggest THC modulates mediotemporal and ventrostriatal function, potentially underlying cannabis's effects on verbal learning and psychosis.
PLoS ONE
June 12, 2013
Philip R. Corlett, Victoria C. Cambridge, Jennifer M. Gardner et al.
104 citations
Delusions, the persistent bizarre beliefs characteristic of psychosis, may arise from disturbances in prediction error-dependent learning. In a placebo-controlled study with 18 human subjects, ketamine—an NMDA receptor antagonist that induces aberrant prediction error signals—was administered during re-exposure to a conditioned fear stimulus. This led to stronger subsequent fear memory compared to placebo, with the degree of strengthening correlating with individual vulnerability to ketamine's psychotogenic effects and with prediction error brain signals. A partial replication in an independent sample with an appetitive learning procedure (8 subjects) supported these findings. The results suggest a link between altered prediction error, memory strength, and psychosis, potentially explaining both the emergence and persistence of delusional beliefs.
Cogn Neuropsychiatry
February 6, 2011
James W. Moore, Danielle C. Turner, Philip R. Corlett et al.
64 citations
Ketamine, a drug that induces temporary psychosis-like symptoms, increased the sense of agency in healthy adults, mimicking the exaggerated action-effect binding seen in schizophrenia. In a small experiment, 14 participants given low-dose ketamine showed greater compression of time between their actions and outcomes compared to placebo. The size of this effect correlated with unusual bodily experiences caused by the drug. The findings suggest ketamine can reproduce certain agency disturbances characteristic of schizophrenia, and that these changes are linked to broader alterations in body awareness.