Effects of topiramate on the association between affect, cannabis craving, and cannabis use in the daily life of youth during a randomized clinical trial

Rationale Topiramate is an anticonvulsant currently under study for treating substance use disorders. Topiramate is thought to reduce substance use by attenuating craving and the rewarding effects of acute substance use through its concurrent GABAergic agonism and glutamatergic antagonism. Importantly, topiramate also impacts mood states central to many models of substance use. Despite this, little previous research has examined whether topiramate attenuates the respective associations of affect and craving with substance use. Objectives We conducted a secondary analysis of 63 youths that exhibited heavy cannabis use, aged 15-24 years, who were randomized in a double-blinded 6-week clinical trial comparing the effects of topiramate (up to 200 mg/day) and placebo on cannabis use. Ecological momentary assessment data were leveraged to model the role positive affect, negative affect, and craving on use over the 6-week period and whether topiramate attenuated associations between these feeling states and cannabis use. Results Findings showed that craving was positively associated with use at the within-person level, while positive affect was negatively associated with use at the between-person level. Topiramate appears to attenuate the negative association of between-person positive affect (i.e., average) and cannabis use. Specifically, those in the placebo condition exhibited this inverse association between average positive affect and use while those in topiramate condition did not. No other significant affect or affect x medication condition interactions were observed. Conclusions These findings implicate craving and low positive affect as important risk factors for cannabis use in youth in treatment. Topiramate may attenuate this association for positive affect.