title: Disruption of frontal θ coherence by Δ9-tetrahydrocannabinol is associated with positive psychotic symptoms.
abstract: The main ingredient in cannabis, Δ(9)-tetrahydrocannabinol (THC), can elicit acute psychotic reactions in healthy individuals and precipitate relapse in schizophrenic patients. However, the neural mechanism of this is unknown. We tested the hypothesis that THC psychopathology is related to changes in electroencephalography (EEG) power or inter-regional coherence. In a within-subjects design, participants (n=16) were given intravenous THC (1.25 mg) or placebo under double-blind conditions, during EEG recordings. Using fast-Fourier transform, EEG data were analyzed for power and coherence in the delta (1-3.5 Hz), theta (3.5-7 Hz), alpha (8-13 Hz), beta (14-25 Hz), low-gamma (30-40 Hz), and high-gamma (60-70 Hz) bands during engagement in the n-back test of working memory (WM). Compared with placebo, THC evoked positive and negative psychotic symptoms, as measured by the positive and negative syndrome scale (p<0.001) and slowed WM performance (p<0.05). Under THC, theta power was specifically reduced, (p<0.001) regardless of WM load; however, the reduction showed no relationship with psychotic symptoms or WM impairment. Coherence between bi-frontal electrodes in the theta band was also reduced by THC (p<0.05) and these reductions correlated with the change-in positive psychotic symptoms (rho=0.79, p<0.001). Bi-frontal specificity was suggested by the absence of a relationship between psychotic symptoms and fronto-parietal coherence. The results reveal that the pro-psychotic effects of THC might be related to impaired network dynamics with impaired communication between the right and left frontal lobes.
authors.affiliation: The Biomedical Research Centre, Institute of Psychiatry, King's College London, Denmark Hill, UK. paul.morrison@iop.kcl.ac.uk
authors.forename: Paul D
authors.initials: PD
authors.lastname: Morrison
authors.forename: Judith
authors.initials: J
authors.lastname: Nottage
authors.forename: James M
authors.initials: JM
authors.lastname: Stone
authors.forename: Sagnik
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Nigel
authors.initials: N
authors.lastname: Tunstall
authors.forename: Rudolf
authors.initials: R
authors.lastname: Brenneisen
authors.forename: David
authors.initials: D
authors.lastname: Holt
authors.forename: Daniel
authors.initials: D
authors.lastname: Wilson
authors.forename: Alex
authors.initials: A
authors.lastname: Sumich
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: Dominic H
authors.initials: DH
authors.lastname: Ffytche
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D013759:Dronabinol / Q000097:blood / Q000633:toxicity*; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D011605:Psychoses, Substance-Induced / Q000097:blood / Q000503:physiopathology* / Q000523:psychology*; D013826:Theta Rhythm / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D013759:Dronabinol