Assessing methamphetamine-related cue reactivity in people with methamphetamine use disorder relative to controls

Methamphetamine use disorder involves methamphetamine-related cues invoking intense craving leading to relapse. Such cue reactivity is thought to arise from Pavlovian conditioning that occurs during the drug-taking experience. Cue reactivity then should be selective to methamphetamine cues (and not other cues), and not observed in people who have never experienced methamphetamine. However, these premises have never been tested and reported using objective measures such as skin conductance response (SCR). The primary aim of this study was to test these premises using a cue reactivity paradigm we developed using control cues. The secondary aim was to explore the relationship between cue reactivity, drug use characteristics, and cognition. Thirty people with a current diagnosis of methamphetamine use disorder and 30 matched controls with no history of substance use disorder were recruited. We observed higher overall subjective reactivity (F = 62.810; p < 0.001) and cueselective physiological reactivity (F = 5.160; p = 0.026) in people with methamphetamine use disorder but not in controls. Co-morbid sedative use was associated with higher subjective craving (r = 0.521; p = 0.003). People who use methamphetamine intravenously had higher cue-selective SCR than smokers (t = 3.750; p < 0.001). Low inhibitory control measured by the Stroop task was associated with increased craving across the cue paradigm (r = -0.494; p = 0.006). Overall, these results support that cue reactivity in people with methamphetamine use disorder is due to Pavlovian conditioning. Its association with drug use and cognition highlights cue reactivity paradigm's utility in understanding methamphetamine use disorder to develop new treatments targeting cue-induced craving.