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Effects of Δ9-Tetrahydrocannabinol on Human Working Memory Function

  • Matthijs G. Bossong
    Affiliations
    Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
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  • J. Martijn Jansma
    Affiliations
    Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
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  • Hendrika H. van Hell
    Affiliations
    Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
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  • Gerry Jager
    Affiliations
    Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands

    Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
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  • Erik Oudman
    Affiliations
    Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
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  • Emi Saliasi
    Affiliations
    Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
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  • René S. Kahn
    Affiliations
    Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
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  • Nick F. Ramsey
    Correspondence
    Address correspondence to Nick F. Ramsey, Ph.D., University Medical Center Utrecht, Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, Heidelberglaan 100, G.03.124, Utrecht 3584 CX, The Netherlands
    Affiliations
    Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
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Published:February 20, 2012DOI:https://doi.org/10.1016/j.biopsych.2012.01.008

      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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      Linked Article

      • Cannabinoids, Working Memory, and Schizophrenia
        Biological PsychiatryVol. 71Issue 8
        • Preview
          In 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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