Delta-9-tetrahydrocannabinol, neural oscillations above 20 Hz and induced acute psychosis

Abstract

Rationale: An acute challenge with delta-9-tetrahydrocannabinol (THC) can induce psychotic symptoms including delusions. High electroencephalography (EEG) frequencies, above 20 Hz, have previously been implicated in psychosis and schizophrenia.

Objectives: The objective of this study is to determine the effect of intravenous THC compared to placebo on high-frequency EEG.

Methods: A double-blind cross-over study design was used. In the resting state, the high-beta to low-gamma magnitude (21-45 Hz) was investigated (n = 13 pairs + 4 THC only). Also, the event-related synchronisation (ERS) of motor-associated high gamma was studied using a self-paced button press task (n = 15).

Results: In the resting state, there was a significant condition × frequency interaction (p = 0.00017), consisting of a shift towards higher frequencies under THC conditions (reduced high beta [21-27 Hz] and increased low gamma [27-45 Hz]). There was also a condition × frequency × location interaction (p = 0.006), such that the reduction in 21-27-Hz magnitude tended to be more prominent in anterior regions, whilst posterior areas tended to show greater 27-45-Hz increases. This effect was correlated with positive symptoms, as assessed on the Positive and Negative Syndrome Scale (PANSS) (r = 0.429, p = 0.042). In the motor task, there was a main effect of THC to increase 65-130-Hz ERS (p = 0.035) over contra-lateral sensorimotor areas, which was driven by increased magnitude in the higher, 85-130-Hz band (p = 0.02) and not the 65-85-Hz band.

Conclusions: The THC-induced shift to faster gamma oscillations may represent an over-activation of the cortex, possibly related to saliency misattribution in the delusional state.

Fig. 1

Bipolar montage used for resting-state analysis. The hatched area denotes electrodes in the anterior group, and the solid fill those in the posterior group. Each line corresponds to a bipolar electrode derivation, such as F7-FCZ or O2-PZ

Fig. 2

Mean spectra over all subjects: a anterior and b posterior. The THC-induced shift in magnitude from below 27 Hz to above 27 Hz is visible in both pairs of spectra

Fig. 3

PANSS scores and observed effects. a, b Association with the ratio of posterior 27–45-Hz magnitude to frontal 20–27-Hz magnitude in the resting state. a Total positive scores. b Total delusion-related scores: P1, P5 and P6. c Motor gamma ERS and positive symptoms. Gray dots are placebo sessions and black triangles are THC sessions. The trend line was fitted for THC sessions only

Fig. 4

Motor event-related synchronisation at a left central location (C3-CZ). The white box highlights the THC-induced increase in 85–130-Hz ERS in the 250 ms after the button press, whilst the black box outlines the 65–85-Hz ERS. The amplitudes have been baseline corrected to the 500 ms before the button press. Scale is in μV/Hz