title: Effects of δ9-tetrahydrocannabinol on human working memory function.
abstract: BACKGROUND
  Evidence indicates involvement of the endocannabinoid (eCB) system in both the pathophysiology of schizophrenia and working memory (WM) function. Additionally, schizophrenia patients exhibit relatively strong WM deficits. These findings suggest the possibility that the eCB system is also involved in WM deficits in schizophrenia. In the present study, we examined if perturbation of the eCB system can induce abnormal WM activity in healthy subjects.
  
  
  METHODS
  A pharmacological functional magnetic resonance imaging study was conducted with a placebo-controlled, cross-over design, investigating effects of the eCB agonist Δ9-tetrahydrocannabinol on WM function in 17 healthy volunteers, by means of a parametric Sternberg item-recognition paradigm with five difficulty levels.
  
  
  RESULTS
  Performance accuracy was significantly reduced after Δ9-tetrahydrocannabinol. In the placebo condition, brain activity increased linearly with rising WM load. Δ9-Tetrahydrocannabinol administration enhanced activity for low WM loads and reduced the linear relationship between WM load and activity in the WM system as a whole and in left dorsolateral prefrontal cortex, inferior temporal gyrus, inferior parietal gyrus, and cerebellum in particular.
  
  
  CONCLUSIONS
  Δ9-Tetrahydrocannabinol enhanced WM activity network-wide for low loads, while reducing the load-dependent response for increasing WM loads. These results indicate that a challenged eCB system can induce both abnormal WM activity and WM performance deficits and provide an argument for the possibility of eCB involvement in WM deficits in schizophrenia.
authors.affiliation: Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands.
authors.forename: Matthijs G
authors.initials: MG
authors.lastname: Bossong
authors.forename: J Martijn
authors.initials: JM
authors.lastname: Jansma
authors.forename: Hendrika H
authors.initials: HH
authors.lastname: van Hell
authors.forename: Gerry
authors.initials: G
authors.lastname: Jager
authors.forename: Erik
authors.initials: E
authors.lastname: Oudman
authors.forename: Emi
authors.initials: E
authors.lastname: Saliasi
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.forename: Nick F
authors.initials: NF
authors.lastname: Ramsey
mesh_terms: D000293:Adolescent; D000328:Adult; D002531:Cerebellum / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects*; D018592:Cross-Over Studies; D013759:Dronabinol / Q000494:pharmacology*; D059907:Functional Neuroimaging; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D021641:Recognition, Psychology / Q000187:drug effects*; D012559:Schizophrenia / Q000503:physiopathology; D055815:Young Adult
chemical_list: D006213:Hallucinogens; D013759:Dronabinol