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.
Key Words
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Article info
Publication history
Published online: February 20, 2012
Accepted:
January 12,
2012
Received in revised form:
December 23,
2011
Received:
July 15,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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- Cannabinoids, Working Memory, and SchizophreniaBiological PsychiatryVol. 71Issue 8
- PreviewIn this issue, Bossong et al. (1) report that delta-9-tetrahydrocannabinol (THC), the primary psychoactive constituent in cannabis, can induce both abnormal working memory (WM) performance and altered brain activity. Based on these findings, they suggest a role for endocannabinoids in both prefrontal cortical function and the pathophysiology of schizophrenia.
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