Objective-To perform a pilot study to examine a range of cognitive flexibility tasks early in cocaine withdrawal.Background-Previous neuropsychological investigations of cocaine withdrawal have conflicted regarding whether impaired cognitive flexibility occurs. However, most studies have examined patients later in withdrawal. Anxiety and yohimbine-induced panic are greatest early in withdrawal, and both anxiety and increased noradrenergic tone can impair cognitive flexibility.

Upregulated noradrenergic activity occurs early in cocaine withdrawal. Our previous work revealed impaired cognitive flexibility in acute cocaine withdrawal, a cognitive domain that appears to be modulated by noradrenergic activity. Therefore, we wished to determine the effect of beta-adrenergic antagonists on cognitive performance in acute cocaine withdrawal. Eleven subjects acutely withdrawing from cocaine were tested in this pilot study on tasks of cognitive flexibility as well as word fluency, attention, verbal memory, and spatial memory, off and on propranolol in a double-blinded manner. Propranolol significantly benefited certain aspects of cognitive flexibility in acute cocaine withdrawal, and improved some measures of verbal fluency and verbal recall. Cocaine withdrawal treatment is characterized by high failure rates. Further research is needed to determine the role this finding of a reversible cognitive impairment in cocaine withdrawal has in treatment.

Recent research revealed decreased access to semantic and associative networks in acute cocaine withdrawal. In autism, such behavioral outcomes are associated with decreased functional connectivity using functional magnetic resonance imaging. Therefore, we wished to determine whether connectivity is also decreased in acute cocaine withdrawal. Eight subjects in acute cocaine withdrawal were compared to controls for connectivity in language areas while performing a task involving categorization of words according to semantic and phonological relatedness. Acute withdrawal subjects had significantly less overall connectivity during semantic relatedness, and a trend towards less connectivity during phonological relatedness. Of potential future interest is whether this might serve as an imaging marker for treatment in patients.