Δ⁹tetrahydrocannabinol impairs visuo-spatial associative learning and spatial working memory in rhesus macaques

Abstract

Cannabis remains the most commonly abused illicit drug and is rapidly expanding in quasi-licit use in some jurisdictions under medical marijuana laws. Effects of the psychoactive constituent Δ9tetrahydrocannabinol (Δ9THC) on cognitive function remain of pressing concern. Prior studies in monkeys have not shown consistent evidence of memory specific effects of Δ9THC on recognition tasks and it remains unclear to what extent Δ9THC causes sedative versus specific cognitive effects. In this study, adult male rhesus monkeys were trained on tasks which assess spatial working memory, visuo-spatial associative memory and learning as well as motivation for food reward. Subjects were subsequently challenged with 0.1-0.3 mg/kg Δ9THC, i.m., in randomized order and evaluated on the behavioral measures. The performance of both vsPAL and SOSS tasks was impaired by Δ9THC in a dose and task-difficulty manner. It is concluded that Δ9THC disrupts cognition in a way that is consistent with a direct effect on memory. There was evidence for interference with spatial working memory, visuo-spatial associative memory and incremental learning in the latter task. These results and the lack of specific effect of Δ9THC in prior visual recognition studies imply a sensitivity of spatial memory processing and/or working memory to endocannabinoid perturbation.

Effects of environmental and pharmacological manipulations on a novel delayed nonmatching-to-sample ‘working memory’ procedure in unrestrained rhesus monkeys

“…Model comparison showed that Δ 9 -THC produced a dose-dependent increase in the slope of the forgetting function. This effect is consistent with an increase in the rate of forgetting reported in DMTS with humans (Lane et al, 2005), DMTS/DNMTS with rodents (Hampson and Deadwyler, 1999) and other working memory procedures with rhesus monkeys (Taffe 2012). Acute administration of methylphenidate failed to systematically alter the forgetting functions over a range of behaviorally active doses.…”

Blood levels do not predict behavioral or physiological effects of Δ9-tetrahydrocannabinol in rhesus monkeys with different patterns of exposure

“…THC impairs performance in a variety of learning- and memory-based operant conditioning tasks in rhesus monkeys (Schulze et al, 1988; Winsauer et al, 1999; Taffe, 2012b). The effects of THC on cognitive performance generally overlap with the doses of THC that produce hypothermia and disruptions in fixed ratio responding in rhesus monkeys (McMahon et al, 2005), although direct comparisons across studies are complicated by differences in THC treatment history, route of administration, and pretreatment time.…”

Chronic periadolescent alcohol consumption produces persistent cognitive deficits in rhesus macaques

“…The procedure used was derived from the self-ordered spatial search (SOSS) task described in Weed et al . (1999) which is sensitive to amnestic drugs such as ketamine and scopolamine (Taffe et al, 1999, Taffe et al, 2002), as well as Δ 9 -tetrahydrocannabinol (Taffe, 2012). Within each session, trials were presented in the following order: 15 2-stimulus trials → 15 3-stimulus trials → 15 2-stimulus trials → 15 3-stimulus trials.…”