Cannabinoids, Neural Synchrony and Information Processing

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DESCRIPTION (provided by applicant): Background: The mechanisms by which cannabinoids produce transient psychotomimetic effects and impairments in attention and memory are not clear. Perceptual, memory and attentional functions are based on distributed processes that are believed to be "bound" together by synchronous high frequency oscillatory activity. In humans, macroscopic neural synchrony can be evaluated non-invasively by entrainment of the EEG to sensory (auditory) stimuli presented of various frequencies. The brain acts as a tuned oscillator, and the steady-state EEG waveform entrains to the frequency and phase of the presented stimulus, providing an indicator of the functioning state of the neural circuits supporting synchrony. Cannabinoids decrease gamma band power in rat hippocampal slices and cannabis users show reduced power in the beta band relative to controls during an auditory entrainment paradigm. We are unaware of any studies examining the acute effects of cannabinoids on EEG neural synchrony in healthy humans. Hypothesis: ?9-THC, in a dose-related manner, will reduce spectral power of the EEG response to an auditory steady state entrainment at 20, 30 and 40 Hz. Secondary analyses will examine the effects of ?9-THC on specific features of the steady state EEG response that may contribute to spectral power reductions including event spectral perturbations (ERSP) and inter-trial phase coherence (ITC). Changes in perceptual alterations, psychotic-like symptoms, and cognitive impairments (attention, verbal recall and working memory) induced by ?9-THC will correlate with changes in spectral power. Methods: Carefully screened healthy individuals will complete 3 test days during which they will receive (0, 0.015, 0.03 mg/kg) ?9-THC in a double-blind, randomized, counterbalanced design. Indices of neural synchrony will be assessed by measurement of EEG spectral power evoked by presentation of auditory click trains at 20, 30 and 40 Hz. Perceptual alterations, psychotic-like symptoms, sustained attention, immediate verbal recall, spatial working memory and visual object recognition memory will also be assessed. Preliminary results: ?9-THC produced a dose-related reduction in power at 30 HZ in response to 30 Hz auditory stimulation (driving). ?9-THC also reduced event related spectral perturbation to 20 and 30 Hz driving. ?9-THC reduced intertrial coherence to 40 Hz driving and to a lesser extent 20 and 30 Hz driving. In a dose- related manner, ?9-THC increased scores on measures of perceptual alterations and psychosis, and induced impairments in measures of verbal recall, spatial working memory, visual recognition memory and attention. Relevance: The aim of this project is to characterize the effects of cannabinoids on electrical communication within the brain (neural synchrony) using EEG in healthy humans and to relate these effects to their behavioral and cognitive effects.