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.

Figure 1

Plasma concentrations of THC (mean±SEM) following the intravenous injection of THC (1.25 mg).

Figure 2

(a) Positive and (b) negative psychotic symptoms (mean±SEM) as measured by the PANSS scale were increased from baseline (time 0 min) following the administration of intravenous THC (1.25 mg).

Figure 3

(a) Accuracy and (b) reaction time in the n-back task (mean±SEM) under THC vs placebo conditions. (a) THC had no effect on accuracy. (b) Performance was slower under THC conditions (p<0.05) and showed an interaction with Task Difficulty (p<0.005).

Figure 4

(a) The effect of THC at each frequency band. Compared with placebo, theta power (mean±SEM) was decreased by THC (p<0.001). Decreases or increases under THC in other frequency bands are not significant. Theta power was reduced regardless of Task Difficulty (b) or recording site (c). Left frontal, LF; right frontal, RF; left central, LC; right central, RC; left temporal, LT; right temporal, RT; left occipitoparietal, LOP; right occipitoparietal, ROP; midline frontal, FZ; midline parietal, PZ; midline central, CZ.

Figure 5

Coherence between left and right prefrontal regions, under THC vs placebo, in the control (0-back) and most challenging (2-back) levels of the n-back task. Bars show coherence (mean±SEM) by frequency. (Diagonal stripes, delta; black, theta; grey, alpha; White, beta.) THC treatment selectively decreased coherence in the theta (p<0.05) and alpha (p<0.05) bands.

Figure 6

Reductions in theta coherence between left and right prefrontal regions under THC was correlated with positive psychotic symptoms (rho=0.79, p<0.001), and survived the removal of two potential outliers (rho=0.69, p=0.006).