Δ9-THC Disrupts Gamma (γ)-Band Neural Oscillations in Humans.

Jose Cortes-Briones, Patrick D Skosnik, Daniel Mathalon, John Cahill, Brian Pittman, Ashley Williams, R Andrew Sewell, Mohini Ranganathan, Brian Roach, Judith Ford, Deepak Cyril D'Souza
Author Information
  1. Jose Cortes-Briones: 1] Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
  2. Patrick D Skosnik: 1] Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA [3] Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA.
  3. Daniel Mathalon: 1] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA [2] Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA [3] Mental Health Service Line, San Francisco VA Medical Center, San Francisco, CA, USA.
  4. John Cahill: 1] Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA [3] Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA.
  5. Brian Pittman: 1] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA [2] Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA.
  6. Ashley Williams: 1] Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT, USA [2] Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA.
  7. R Andrew Sewell: 1] Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA [3] Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA.
  8. Mohini Ranganathan: 1] Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA [3] Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA.
  9. Brian Roach: 1] Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA [2] Mental Health Service Line, San Francisco VA Medical Center, San Francisco, CA, USA.
  10. Judith Ford: 1] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA [2] Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA [3] Mental Health Service Line, San Francisco VA Medical Center, San Francisco, CA, USA.
  11. Deepak Cyril D'Souza: 1] Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA [3] Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA.

Abstract

Gamma (γ)-band oscillations play a key role in perception, associative learning, and conscious awareness and have been shown to be disrupted by cannabinoids in animal studies. The goal of this study was to determine whether cannabinoids disrupt γ-oscillations in humans and whether these effects relate to their psychosis-relevant behavioral effects. The acute, dose-related effects of Δ-9-tetrahydrocannabinol (Δ(9)-THC) on the auditory steady-state response (ASSR) were studied in humans (n=20) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, 0.015, and 0.03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. Electroencephalography (EEG) was recorded while subjects listened to auditory click trains presented at 20, 30, and 40 Hz. Psychosis-relevant effects were measured with the Positive and Negative Syndrome scale (PANSS). Δ(9)-THC (0.03 mg/kg) reduced intertrial coherence (ITC) in the 40 Hz condition compared with 0.015 mg/kg and placebo. No significant effects were detected for 30 and 20 Hz stimulation. Furthermore, there was a negative correlation between 40 Hz ITC and PANSS subscales and total scores under the influence of Δ(9)-THC. Δ(9)-THC (0.03 mg/kg) reduced evoked power during 40 Hz stimulation at a trend level. Recent users of cannabis showed blunted Δ(9)-THC effects on ITC and evoked power. We show for the first time in humans that cannabinoids disrupt γ-band neural oscillations. Furthermore, there is a relationship between disruption of γ-band neural oscillations and psychosis-relevant phenomena induced by cannabinoids. These findings add to a growing literature suggesting some overlap between the acute effects of cannabinoids and the behavioral and psychophysiological alterations observed in psychotic disorders.

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Grants

  1. R21 DA020750/NIDA NIH HHS
  2. VA999999/Intramural VA

MeSH Term

Acoustic Stimulation
Adolescent
Adult
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Dronabinol
Electroencephalography
Female
Fourier Analysis
Gamma Rhythm
Humans
Male
Psychiatric Status Rating Scales
Psychoacoustics
Psychotropic Drugs
Young Adult

Chemicals

Psychotropic Drugs
Dronabinol
delta(9)-tetrahydrocannabinolic acid

Word Cloud

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