A milestone in cannabis research is the establishment of a clinically relevant cannabis withdrawal syndrome, yet little is known about the underlying mechanisms. We investigated the predictive role of mental health and cognitive factors in withdrawal severity during an active attempt to cut down, relative to uninterrupted cannabis use. Ninety heavy cannabis users were randomly assigned to an experimental or control group. The experimental group was asked to cut down substance use for 1 week. Past week substance use, substance use-related problems, depressive symptoms, cravings, and cognitive control were assessed at baseline. Past week substance use and withdrawal severity were assessed at follow-up. The experimental group reduced their cannabis use more and experienced more withdrawal than the control group. Hierarchical regression analysis per predictor indicated that cannabis use-related problems, depressive symptoms, and cannabis craving, but not cognitive control, predicted stronger withdrawal. Craving uniquely predicted withdrawal in the experimental group. A combined hierarchical regression indicated that only depressive symptoms and cannabis use-related problems uniquely predicted withdrawal across groups. These results suggest that depressive symptoms and cannabis use-related problems are generally indicative of cannabis withdrawal severity, whereas craving specifically predicts cannabis withdrawal during an active attempt to cut-down cannabis use.