Marijuana (MJ) acutely acts on cannabinoid receptors that are found in numerous brain regions, including those involved in reward processing and decision-making. However, it remains unclear how long-term, chronic MJ use alters reward-based decision-making. In the present study, using [15 O]water PET imaging, we measured brain activity in chronic MJ users, who underwent monitored abstinence from MJ for approximately 24 h before imaging, and control participants, while they took part in the Iowa Gambling Task (IGT), a monetary decision making task that strongly relies on the ventromedial prefrontal cortex (vmPFC). During PET imaging, participants took part in the standard and a variant version of the IGT as well as a control task. Chronic MJ users performed equally well on the standard IGT, but significantly worse than controls on the variant IGT. Chronic MJ users and control subjects showed increased regional cerebral blood flow (rCBF) in the vmPFC on both versions of the IGT compared to the control task. In the two-group comparison, chronic MJ users showed significantly greater rCBF than controls in the vmPFC on the standard IGT and greater activity in the cerebellum on both versions of the IGT. Furthermore, duration of use, but not age of first use, was associated with greater activity in the vmPFC. Thus, chronic MJ users tend to strongly recruit neural circuitry involved in decision-making and reward processing (vmPFC), and probabilistic learning (cerebellum) when performing the IGT. Neuropsychopharmacology (2012) 37, 618-629; doi:10.1038/npp.2011.227; published online 28 September 2011Keywords: marijuana; decision-making; ventromedial prefrontal cortex; chronic use; cerebellum; PET
INTRODUCTIONMarijuana (MJ) is the most commonly used illicit drug in the Unites States (National Survey on Drug Use and Health, 2008). The acute effects of MJ are thought to involve the action of delta-9-tetra-hydrocannabinol (THC) on CB 1 receptors located principally on axons and nerve terminals (Mechoulam, 1970;Matsuda et al, 1990;Iversen, 2003) in a number of regions, including the frontal cortex, hippocampus, and cerebellum (Iversen, 2003;Eggan and Lewis, 2007). However, the long-term impact of chronic MJ use on the brain remains poorly understood, especially with regard to more complex decision-making processes. In the present study, using [ 15 O]water PET imaging, we measured brain activity in a large sample of chronic MJ users and controls while participants performed the Iowa Gambling Task (IGT) (Bechara et al, 1994), a commonly used measure of complex monetary decision-making. In addition to group comparisons, correlational analyses were conducted to investigate the association of two key variablesFage of first MJ use and duration of MJ useFwith brain activity.Chronic MJ users, tested after brief abstinence periods, generally perform poorly on the IGT (Fridberg et al, 2010;Wesley et al, 2011;Whitlow et al, 2004). One study found that performance was poor even after a 25-day period of abstinence (Bolla et al, 2005). In ad...