The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans.
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.
Psychiatry Service, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Jose A
JA
Cortes-Briones
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.
John D
JD
Cahill
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.
Patrick D
PD
Skosnik
Department of Psychiatry, University of California San Francisco, California; Mental Health Service, San Francisco Veterans Affairs Medical Center, San Francisco, California.
Daniel H
DH
Mathalon
Psychiatry Service, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut.
Ashley
A
Williams
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.
R Andrew
RA
Sewell
Mental Health Service, San Francisco Veterans Affairs Medical Center, San Francisco, California.
Brian J
BJ
Roach
Department of Psychiatry, University of California San Francisco, California; Mental Health Service, San Francisco Veterans Affairs Medical Center, San Francisco, California.
Judith M
JM
Ford
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.
Mohini
M
Ranganathan
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.
Deepak Cyril
DC
D'Souza
D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000009:adverse effects*; D004569:Electroencephalography; D005260:Female; D006213:Hallucinogens / Q000009:adverse effects*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D009622:Noise; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000209:etiology* / Q000473:pathology; D055815:Young Adult
D006213:Hallucinogens; D013759:Dronabinol
Cannabinoids; Electroencephalogram; Neural noise; Nonlinear analysis; Psychosis; Tetrahydrocannabinol