Divergent Effects of Oral Cannabis Oil Extracts Marketed as C. Indica or C. Sativa on Exertion of Cognitive Effort in Rats

Abstract

The main psychoactive compound within the cannabis plant, Δ9-tetrahydrocannabinol (THC), is thought to drive both the sensation of “high” and the cognitive impairments associated with cannabis consumption. Researchers keen to understand howcannabis impairs cognition have, therefore, studied the behavioral effects of systemic injections of THC in animal models. However, cannabis contains multiple other cannabinoids which may critically modulate the resulting cognitive effects. Users also typically eat or smoke cannabis, leading to concern over the translational validity of pure THC injections. We, therefore, tested whether acute oral administration of two different commercially available cannabis extracts, marketed as C. indica or C. sativa, decreased male Long-Evans rats’ willingness to exert greater cognitive effort in order to maximize reward earned, as expected from previous experiments using injected THC. Both oils were matched for THC and cannabidiol content. While both cannabis products slowed response times at higher doses, only C. indica oil at the highest dose administered (10 mg/kg THC) decreased the number of trials on which rats chose to complete high-effort/high-reward trials. Repeated dosing with a medium dose of either cannabinoid product (3 mg/kg THC) did not influence choice. Ex vivo analyses confirmed comparable levels of brain THC after C. indica or C. sativa administration. Although controversial in the field, these results support the suggestion that products marketed as different cannabis cultivars have dissociable cognitive effects that may not resemble pure THC and emphasize the importance of the route of administration in experimental design.