Neuroimaging Evidence for Cannabinoid Modulation of Cognition and Affect in Man

Cannabinoid receptors (CB1 and CB2) are ubiquitous within the brain (Wilson and Nicoll, 2002; Eggan and Lewis, 2007). Their distribution and role in the modulation of different neurotransmitter systems (Pertwee and Ross, 2002; Pertwee, 2008a) clearly indicate that cannabinoids are involved in the modulation of different cognitive and emotional processes (Solowij and Michie, 2007). The role of the endocannabinoid system in this has attracted the attention of basic scientists for decades (Zanettini et al., 2011). The modulation of cognitive and emotional processes in man by the extracts of Cannabis sativa (C sativa), the most commonly used illicit drug consumed by an estimated 4% of the adult population worldwide (Copeland and Swift, 2009), has also been known for a long time and extensively investigated in experimental and observational studies (Solowij, 1998; Ranganathan and D’Souza, 2006; Solowij and Michie, 2007; Crippa et al., 2009; D’Souza et al., 2009). However, only over the last 20 years has it been possible to precisely investigate the neural basis of the acute effects of cannabinoids on cognition by employing sophisticated neuroimaging techniques (Bhattacharyya et al., 2009a, 2012a; MartinSantos et al., 2010). A renewed interest in the link between regular cannabis use and development of psychotic disorders has provided further impetus, coupled with interest in the therapeutic potential of certain cannabinoids. Pharmacological challenge studies involving the administration of cannabinoids present in the extract of C sativa or their synthetic counterparts in combination with neuroimaging have served to complement current understanding regarding the role of the endocannabinoid system in regulating human cognitive and emotional processes (Zanettini et al., 2011), to model aspects of various psychiatric illnesses in man and understand their neural underpinnings (Bhattacharyya et al., 2009a). Among the more than 60 different cannabinoids (Mechoulam and Gaoni, 1967) present in the extract of C sativa, delta-9-tetrahydrocanabinol (THC) is thought to be responsible for most of the psychotropic effects of cannabis (Mechoulam et al., 1970) and modulation of cognitive domains such as learning and memory (Hall and Solowij, 1998; Curran et al., 2002; Ranganathan and D’Souza, 2006), psychomotor control (Hart et al., 2001; McDonald et al., 2003; Ramaekers et al., 2006, 2009), and attention (Hall and Solowij, 1998; Ilan et al., 2004), as evident from systematic acute experimental studies. The purpose of this article is to provide a brief critical overview of current neuroimaging evidence of the acute effects of THC in man as evident from neuroimaging studies. The studies are organized into groups based on neuroimaging domains examined.