Delta-9-tetrahydrocannabinol-induced dopamine release as a function of psychosis risk: 18F-fallypride positron emission tomography study

PLoS One. 2013 Jul 25;8(7):e70378. doi: 10.1371/journal.pone.0070378. Print 2013.

Abstract

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 (18)F-fallypride to test the hypothesis that genetic risk for psychosis is expressed by differential induction of dopamine release by Δ(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 Δ(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 (18)F-fallypride displacement. Voxel-based statistical maps, representing specific D2/3 binding changes, were computed to localize areas with increased ligand displacement after Δ(9)-THC administration, reflecting dopamine release. While Δ(9)-THC was not associated with dopamine release in the control group, significant ligand displacement induced by Δ(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 Δ(9)-THC in terms of increased endogenous dopamine release in individuals at risk for psychosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Benzamides*
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / drug effects*
  • Caudate Nucleus / metabolism
  • Dopamine / metabolism*
  • Dronabinol / pharmacology*
  • Female
  • Fluorine Radioisotopes
  • Humans
  • Male
  • Positron-Emission Tomography
  • Psychotic Disorders / diagnostic imaging
  • Psychotic Disorders / metabolism*
  • Psychotic Disorders / psychology
  • Pyrrolidines*
  • Radiopharmaceuticals*
  • Risk Factors
  • Substance-Related Disorders / diagnostic imaging
  • Substance-Related Disorders / metabolism*
  • Substance-Related Disorders / psychology

Substances

  • Benzamides
  • Fluorine Radioisotopes
  • N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide
  • Pyrrolidines
  • Radiopharmaceuticals
  • Dronabinol
  • Dopamine

Grant support

The work was supported by a grant of NWO, the Dutch council for scientific research (ZonMW VENI grant to C. Henquet). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.