title: Δ9-THC Disrupts Gamma (γ)-Band Neural Oscillations in Humans.
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.
authors.affiliation: 1] Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Cortes-Briones
authors.affiliation: 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.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Skosnik
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mathalon
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Cahill
authors.affiliation: 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.
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.affiliation: 1] Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT, USA [2] Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Williams
authors.affiliation: 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.
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Sewell
authors.affiliation: 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.
authors.forename: Mohini
authors.initials: M
authors.lastname: Ranganathan
authors.affiliation: 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.
authors.forename: Brian
authors.initials: B
authors.lastname: Roach
authors.affiliation: 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.
authors.forename: Judith
authors.initials: J
authors.lastname: Ford
authors.affiliation: 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.
authors.forename: Deepak Cyril
authors.initials: DC
authors.lastname: D'Souza
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D004569:Electroencephalography; D005260:Female; D005583:Fourier Analysis; D065818:Gamma Rhythm / Q000187:drug effects*; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D011571:Psychoacoustics; D011619:Psychotropic Drugs / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D011619:Psychotropic Drugs; D013759:Dronabinol; C025351:delta(9)-tetrahydrocannabinolic acid