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.

journal_name

Biol Psychiatry

journal_title

Biological psychiatry

authors

Bossong MG,Jansma JM,van Hell HH,Jager G,Oudman E,Saliasi E,Kahn RS,Ramsey NF

doi

10.1016/j.biopsych.2012.01.008

subject

Has Abstract

pub_date

2012-04-15 00:00:00

pages

693-9

issue

8

eissn

0006-3223

issn

1873-2402

pii

S0006-3223(12)00046-7

journal_volume

71

pub_type

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