Effects of acute oral Δ9-tetrahydrocannabinol and standardized cannabis extract on the auditory P300 event-related potential in healthy volunteers

Reduced amplitudes of auditory evoked P300 are a robust finding in schizophrenic patients, indicating deficient attentional resource allocation and active working memory. Δ9-Tetrahydrocannabinol (Δ9-THC), the main active constituent of Cannabis sativa, has been known to acutely impair cognitive abilities in several domains, particularly in memory and attention. Given the psychotic-like effects of Δ9-THC, a cannabinoid hypothesis of schizophrenia has been proposed. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on P300 amplitude in 20 healthy volunteers (age 28.2 ± 3.1 years, 10 male) by comparing Δ9-THC and standardized cannabis extract containing Δ9-THC and cannabidiol (CBD). P300 waves were recorded during a choice reaction task. As expected, Δ9-THC revealed a significant reduction of P300 amplitude at midline frontal, central, and parietal electrodes. CBD has been known to abolish many of the psychotropic effects of Δ9-THC, but, unexpectedly, failed to demonstrate a reversal of Δ9-THC-induced P300 reduction. Moreover, there were no correlations between cannabinoid plasma concentrations and P300 parameters. These data suggest that Δ9-THC may lead to acute impairment of attentional functioning and working memory. It can be speculated whether the lack of effect of CBD may be due to an insufficient dose used or to an involvement of neurotransmitter systems in P300 generation which are not influenced by CBD.