TY - JOUR
T1 - Delta-9-Tetrahydrocannabinol-Induced Dopamine Release as a Function of Psychosis Risk: F-18-Fallypride Positron Emission Tomography Study
AU - Kuepper, Rebecca
AU - Ceccarini, Jenny
AU - Lataster, Johan
AU - van Os, Jim
AU - van Kroonenburgh, Marinus
AU - van Gerven, Joop M. A.
AU - Marcelis, Machteld
AU - Van Laere, Koen
AU - Henquet, Cecile
PY - 2013/7/25
Y1 - 2013/7/25
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0070378
DO - 10.1371/journal.pone.0070378
M3 - Article
C2 - 23936196
SN - 1932-6203
VL - 8
JO - PLOS ONE
JF - PLOS ONE
IS - 7
M1 - e70378
ER -