An fMRI Study of SYN115 in Cocaine Dependent Subjects

The dopamine system is critical in modulation of reward and has been implicated in the
initiation and maintenance of addiction (Volkow et al 2004). Medications that increase
dopamine either directly or indirectly have been shown to have preliminary efficacy at
reducing cocaine use in cocaine dependent subjects (Grabowski et al 2004a; Schmitz et al
2008). A novel class of medications that has recently been shown to indirectly modulate
dopamine function is adenosine A2A receptor antagonists (Fuxe et al 2007). Based on their
effect on dopamine function it has been suggested that these compounds may be efficacious in
the treatment of drug addiction (Ferre et al 2007c). Before clinical efficacy studies are
undertaken, more basic research on the effects of adenosine A2A antagonists on brain
function and behavior are warranted. The aim of this study is to examine the acute effects
of a single dose of the selective adenosine A2A antagonist (SYN115, Synosia Therapeutics,
Chemical name: 4-Hydroxy-4-methyl-piperidine-1-carboxylic
acid-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide) on brain function and behavior in
cocaine dependent individuals using functional magnetic resonance imaging (fMRI). To examine
the effect of a single dose of SYN115 on brain function and behavior in cocaine dependent
subjects.

Hypotheses:

1. SYN115 100 mg will increase brain activation in the dorsolateral prefrontal cortex
compared to placebo in cocaine dependent subjects performing a working memory task.

2. SYN115 100 mg will increase brain activation in the ventral striatum compared to
placebo in cocaine dependent subjects performing a reversal learning task.

3. SYN115 100 mg will reduce brain activation in the anterior cingulate gyrus and amygdala
compared to placebo in cocaine dependent subjects performing a cocaine-word Stroop
task.