Delta-9-Tetrahydrocannabinol-Induced Dopamine Release as a Function of Psychosis Risk: F-18-Fallypride Positron Emission Tomography Study

Rebecca Kuepper*, Jenny Ceccarini, Johan Lataster, Jim van Os, Marinus van Kroonenburgh, Joop M. A. van Gerven, Machteld Marcelis, Koen Van Laere, Cecile Henquet

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Cannabis use is associated with psychosis, particularly in those with expression of, or vulnerability for, psychotic illness. The biological underpinnings of these differential associations, however, remain largely unknown. We used Positron Emission Tomography and F-18-fallypride to test the hypothesis that genetic risk for psychosis is expressed by differential induction of dopamine release by Delta(9)-THC (delta-9-tetrahydrocannabinol, the main psychoactive ingredient of cannabis). In a single dynamic PET scanning session, striatal dopamine release after pulmonary administration of Delta(9)-THC was measured in 9 healthy cannabis users (average risk psychotic disorder), 8 patients with psychotic disorder (high risk psychotic disorder) and 7 un-related first-degree relatives (intermediate risk psychotic disorder). PET data were analyzed applying the linear extension of the simplified reference region model (LSRRM), which accounts for time-dependent changes in F-18-fallypride displacement. Voxel-based statistical maps, representing specific D-2/3 binding changes, were computed to localize areas with increased ligand displacement after Delta(9)-THC administration, reflecting dopamine release. While Delta(9)-THC was not associated with dopamine release in the control group, significant ligand displacement induced by Delta(9)-THC in striatal subregions, indicative of dopamine release, was detected in both patients and relatives. This was most pronounced in caudate nucleus. This is the first study to demonstrate differential sensitivity to Delta(9)-THC in terms of increased endogenous dopamine release in individuals at risk for psychosis.
Original languageEnglish
Article numbere70378
Issue number7
Publication statusPublished - 25 Jul 2013


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