Marijuana (Cannabis sativa) and its primary psychoactive component, ␦-9-tetrahydrocannabinol (⌬ 9 -THC), have long been known to disrupt cognition in humans. Although ⌬ 9 -THC and other cannabinoids disrupt performance in a wide range of animal models of learning and memory, few studies have investigated the effects of smoked marijuana in these paradigms. Moreover, in preclinical studies, cannabinoids are generally administered before acquisition, and because retention is generally evaluated soon afterward, it is difficult to distinguish between processes related to acquisition and retrieval. In the present study, we investigated the specific effects of marijuana smoke and injected ⌬ 9 -THC on acquisition versus memory retrieval in a mouse repeated acquisition Morris water-maze task. To distinguish between these processes, subjects were administered ⌬ 9 -THC or they were exposed to marijuana smoke either 30 min before acquisition or 30 min before the retention test. Inhalation of marijuana smoke or injected ⌬ 9 -THC impaired the ability of the mice to learn the location of the hidden platform and to recall the platform location once learning had already taken place. In contrast, neither drug impaired performance in a cued task in which the platform was made visible. Finally, the cannabinoid-1 (CB 1 ) receptor antagonist
N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (rimonabant) blocked the memory disruptive effects of both ⌬ 9 -THC and marijuana. These data represent the first evidence demonstrating that marijuana impairs memory retrieval through a CB 1 receptor mechanism of action and independently of its effects on sensorimotor performance, motivation, and initial acquisition.Marijuana (Cannabis sativa) produces a constellation of effects in humans, including alterations in perception and mood, intoxication, euphoria, increased heart rate, physical dependence upon chronic use, and cognitive impairment (Pacher et al., 2006;Ranganathan and D'Souza, 2006). During the more than 40 years since ⌬ 9 -tetrahydrocannabinol (⌬ 9 -THC) was first identified as marijuana's primary psychoactive ingredient (Gaoni and Mechoulam, 1964), great strides have been made in understanding its actions in the brain. ⌬ 9 -THC and related chemicals, known as cannabinoids, produce their psychoactive effects by acting at the cannabinoid-1 (CB 1 ) receptor in brain areas associated with learning and memory and elsewhere (Herkenham, 1991). Particular interest has focused on the effects of cannabis on cognition, because both naturally occurring and synthetically derived cannabinoids disrupt performance in a variety of rodent spatial (Lichtman et al