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The Psychosis-like Effects of Δ9-Tetrahydrocannabinol Are Associated With Increased Cortical Noise in Healthy Humans

  • Jose A. Cortes-Briones
    Affiliations
    Psychiatry Service, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut

    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
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  • John D. Cahill
    Affiliations
    Psychiatry Service, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut

    Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut

    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
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  • Patrick D. Skosnik
    Affiliations
    Psychiatry Service, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut

    Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut

    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
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  • Daniel H. Mathalon
    Affiliations
    Department of Psychiatry, University of California San Francisco, California

    Mental Health Service, San Francisco Veterans Affairs Medical Center, San Francisco, California
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  • Ashley Williams
    Affiliations
    Psychiatry Service, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut

    Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut
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  • R. Andrew Sewell
    Affiliations
    Psychiatry Service, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut

    Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut

    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
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  • Brian J. Roach
    Affiliations
    Mental Health Service, San Francisco Veterans Affairs Medical Center, San Francisco, California
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  • Judith M. Ford
    Affiliations
    Department of Psychiatry, University of California San Francisco, California

    Mental Health Service, San Francisco Veterans Affairs Medical Center, San Francisco, California
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  • Mohini Ranganathan
    Affiliations
    Psychiatry Service, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut

    Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut

    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
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  • Deepak Cyril D’Souza
    Correspondence
    Address correspondence to Deepak Cyril D’Souza, M.D., Yale University, VACHS Psychiatry 116A, 950 Campbell Avenue, West Haven, CT 06516
    Affiliations
    Psychiatry Service, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut

    Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut

    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
    Search for articles by this author

      Abstract

      Background

      Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Δ9-THC), the principal active constituent of cannabis.

      Methods

      Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Δ9-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ9-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design.

      Results

      Δ9-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Δ9-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ9-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms.

      Conclusions

      At doses that produced psychosis-like effects, Δ9-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ9-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Δ9-THC.

      Keywords

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