Community-based studies suggest that cannabis products that are high in Δ⁹-tetrahydrocannabinol (THC) but low in cannabidiol (CBD) are particularly hazardous for mental health. Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions. In a between-subjects design, we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment. Healthy participants were randomised to receive oral CBD 600 mg (n=22) or placebo (n=26), 210 min ahead of intravenous (IV) THC (1.5 mg). Post-THC, there were lower PANSS positive scores in the CBD group, but this did not reach statistical significance. However, clinically significant positive psychotic symptoms (defined a priori as increases ≥ 3 points) were less likely in the CBD group compared with the placebo group, odds ratio (OR)=0.22 (χ²=4.74, p<0.05). In agreement, post-THC paranoia, as rated with the State Social Paranoia Scale (SSPS), was less in the CBD group compared with the placebo group (t=2.28, p<0.05). Episodic memory, indexed by scores on the Hopkins Verbal Learning Task-revised (HVLT-R), was poorer, relative to baseline, in the placebo pre-treated group (-10.6 ± 18.9%) compared with the CBD group (-0.4% ± 9.7 %) (t=2.39, p<0.05). These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health.

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.

Abnormal gamma oscillations, measured by electroencephalography (EEG), have been associated with chronic psychotic disorders, but their prevalence in the early phase of psychosis is less clear. We sought to address this by systematically reviewing the relevant literature. We searched for EEG studies of gamma band oscillations in subjects at high risk for psychosis and in patients with first episode psychosis. The following measures of gamma oscillations were extracted: resting power, evoked power, induced power, connectivity and peak frequency. Forty-five studies with a total of 3099 participants were included. There were potential sources of bias in the study designs and potential artefacts. Although there were few consistent findings, several studies reported decreased evoked or induced power in both high risk subjects and first episode patients. Studies using larger samples with serial EEG measurements, and designs that minimise artefacts that occur at the gamma frequency may advance work in this area.

BackgroundFinding reliable endophenotypes for psychosis could lead to an improved understanding of aetiology, and provide useful alternative phenotypes for genetic association studies. Resting quantitative electroencephalography (QEEG) activity has been shown to be heritable and reliable over time. However, QEEG research in patients with psychosis has shown inconsistent and even contradictory findings, and studies of at-risk populations are scarce. Hence, this study aimed to investigate whether resting QEEG activity represents a candidate endophenotype for psychosis.MethodQEEG activity at rest was compared in four frequency bands (delta, theta, alpha, and beta), between chronic patients with psychosis (N = 48), first episode patients (N = 46), at-risk populations (“at risk mental state”, N = 33; healthy relatives of patients, N = 45), and healthy controls (N = 107).ResultsResults showed that chronic patients had significantly increased resting QEEG amplitudes in delta and theta frequencies compared to healthy controls. However, first episode patients and at-risk populations did not differ from controls in these frequency bands. There were no group differences in alpha or beta frequency bands.ConclusionSince no abnormalities were found in first episode patients, ARMS, or healthy relatives, resting QEEG activity in the frequency bands examined is unlikely to be related to genetic predisposition to psychosis. Rather than endophenotypes, the low frequency abnormalities observed in chronic patients are probably related to illness progression and/or to the long-term effects of treatments.