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The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans.
Biol Psychiatry 2015; 78(11):805-13BP

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 (Δ(9)-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 Δ(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design.

RESULTS

Δ(9)-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 Δ(9)-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ(9)-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, Δ(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ(9)-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 Δ(9)-THC.

Authors+Show Affiliations

Psychiatry Service, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.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.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.Department of Psychiatry, University of California San Francisco, California; Mental Health Service, San Francisco Veterans Affairs Medical Center, San Francisco, California.Psychiatry Service, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut.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.Mental Health Service, San Francisco Veterans Affairs Medical Center, San Francisco, California.Department of Psychiatry, University of California San Francisco, California; Mental Health Service, San Francisco Veterans Affairs Medical Center, San Francisco, California.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.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. Electronic address: deepak.dsouza@yale.edu.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

25913109

Citation

Cortes-Briones, Jose A., et al. "The Psychosis-like Effects of Δ(9)-tetrahydrocannabinol Are Associated With Increased Cortical Noise in Healthy Humans." Biological Psychiatry, vol. 78, no. 11, 2015, pp. 805-13.
Cortes-Briones JA, Cahill JD, Skosnik PD, et al. The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans. Biol Psychiatry. 2015;78(11):805-13.
Cortes-Briones, J. A., Cahill, J. D., Skosnik, P. D., Mathalon, D. H., Williams, A., Sewell, R. A., ... D'Souza, D. C. (2015). The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans. Biological Psychiatry, 78(11), pp. 805-13. doi:10.1016/j.biopsych.2015.03.023.
Cortes-Briones JA, et al. The Psychosis-like Effects of Δ(9)-tetrahydrocannabinol Are Associated With Increased Cortical Noise in Healthy Humans. Biol Psychiatry. 2015 Dec 1;78(11):805-13. PubMed PMID: 25913109.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans. AU - Cortes-Briones,Jose A, AU - Cahill,John D, AU - Skosnik,Patrick D, AU - Mathalon,Daniel H, AU - Williams,Ashley, AU - Sewell,R Andrew, AU - Roach,Brian J, AU - Ford,Judith M, AU - Ranganathan,Mohini, AU - D'Souza,Deepak Cyril, Y1 - 2015/03/30/ PY - 2014/09/04/received PY - 2015/03/06/revised PY - 2015/03/20/accepted PY - 2015/4/28/entrez PY - 2015/4/29/pubmed PY - 2016/8/12/medline KW - Cannabinoids KW - Electroencephalogram KW - Neural noise KW - Nonlinear analysis KW - Psychosis KW - Tetrahydrocannabinol SP - 805 EP - 13 JF - Biological psychiatry JO - Biol. Psychiatry VL - 78 IS - 11 N2 - 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 (Δ(9)-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 Δ(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. RESULTS: Δ(9)-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 Δ(9)-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ(9)-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, Δ(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ(9)-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 Δ(9)-THC. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/25913109/The_psychosis_like_effects_of_Δ_9__tetrahydrocannabinol_are_associated_with_increased_cortical_noise_in_healthy_humans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(15)00269-3 DB - PRIME DP - Unbound Medicine ER -