Δ9Tetrahydrocannabinol impairs reversal learning but not extra-dimensional shifts in rhesus macaques

Expansion of medical marijuana use in the US and the recently successful decriminalization of recreational marijuana in two States elevates interest in the specific cognitive effects of Δ9tetrahydrocannabinol (Δ9THC), the major psychoactive constituent of marijuana. Controlled laboratory studies in nonhuman primates provide mixed evidence for specific effects of Δ9THC in learning and memory tasks, with a suggestion that frontal-mediated tasks may be the most sensitive. In this study, adult male rhesus monkeys were trained on tasks which assess reversal learning, extradimensional attentional shift learning and spatial delayed-response. Subjects were challenged with 0.1–0.5 mg/kg Δ9THC, i.m., in randomized order and evaluated on the behavioral measures. Peak plasma levels of Δ9THC were observed 30 min after 0.2 mg/kg (69 ± 29 ng/ml) and 60 min after 0.5 mg/kg (121 ± 23 ng/ml) was administered and behavioral effects on a bimanual motor task persisted for up to 2 h after injection. An increase in errors-to-criterion (ETC) associated with reversal learning was further increased by Δ9THC in a dose-dependent manner. The increase in ETC associated with extradimensional shifts was not affected by Δ9THC. Spatial delayed-response performance was impaired by Δ9THC in a retention-interval-dependent manner. Overall the pattern of results suggests a more profound effect of Δ9THC on tasks mediated by orbitofrontal (reversal learning) versus dorsolateral (extradimensional shifts) prefrontal mechanisms.

► Medical marijuana, and recreational legalization in two US States, will increase use.
► There is need to delineate specific cognitive effects of Δ9tetrahydrocannabinol (THC).
► This study examined executive function tasks which rely upon the prefrontal cortex.
► THC impaired reversal learning without affecting extradimensional shifts of attention.
► THC affects functions mediated by orbitofrontal over dorsolateral prefrontal regions.