Opposite Roles for Cannabidiol and δ-9-Tetrahydrocannabinol in Psychotomimetic Effects of Cannabis Extracts: A Naturalistic Controlled Study

Background: Although δ-9-tetrahydrocannabinol (THC), the main cannabinoid from the cannabis plant, is responsible for the psychotomimetic effects of cannabis, cannabidiol (CBD), the second most abundant cannabinoid in the cannabis plant, does not show any psychotomimetic effect. Cannabidiol has even been proposed to be antipsychotic and to counteract some of the psychotomimetic effects of THC. The aim of this study was to test the potential antipsychotomimetic effects of CBD.

Method: Eighteen members from a cannabis social club were tested for subjective and psychotomimetic effects under the effects of different full-spectrum cannabis extracts containing either THC, CBD, THC + CBD, or placebo in a naturalistic, randomized, double-blind, crossover, placebo-controlled study.

Results: Results showed that participants under the effects of THC + CBD showed lower psychotomimetic scores in subjective scales when compared with THC alone. Subjective scores were lower under the effects of CBD and placebo when compared with THC + CBD. Cannabidiol and placebo did not show any psychotomimetic effect.

Conclusions: This study provides evidence for both the psychotomimetic effects of THC and the antipsychotomimetic effects of CBD when it is coadministered with THC in real-world situations, which can be very relevant for the clinical practice of medical cannabis. Ultimately, this study substantiates the link between the endocannabinoid system and psychotic-like symptoms and has important implications for the understanding of schizophrenia and the therapeutic potential of CBD as an antipsychotic. Lastly, we demonstrate how reliable methodologies can be implemented in real situations to collect valid ecological evidence outside classic laboratory settings.