Involvement of dopamine in regulating exploration during decision-making has long been hypothesized, but direct causal evidence in humans is still lacking. Here, we use a combination of computational modeling, pharmacological intervention and functional magnetic resonance imaging to address this issue. Thirty-one healthy male participants performed a restless four-armed bandit task in a within-subjects design under three drug conditions: 150 mg of the dopamine precursor L-dopa, 2 mg of the D2 receptor antagonist haloperidol, and placebo. Choices were best explained by an extension of an established Bayesian learning model accounting for perseveration, directed exploration and random exploration. Modeling revealed attenuated directed exploration under L-dopa, while neural signatures of exploration, exploitation and prediction error were unaffected. Instead, L-dopa attenuated neural representations of overall uncertainty in insula and dorsal anterior cingulate cortex. Our results highlight the computational role of these regions in exploration and suggest that dopamine modulates how this circuit tracks accumulating uncertainty during decision-making.

Findings on neurocognitive effects of sustained cannabis use are heterogeneous. Previous work has rarely taken time of abstinence into account. In this review, we focus on understanding sustained effects of cannabis, which begin when clinical symptoms of the drug have worn off after at least 14 days. We conducted a search between 2004 and 2015 and found 38 studies with such a prolonged abstinence phase. Study-design quality in terms of evidence-based medicine is similar among studies. Studies found some attention or concentration deficits in cannabis users (CU). There is evidence that chronic CU might experience sustained deficits in memory function. Findings are mixed regarding impairments in inhibition, impulsivity and decision making for CU, but there is a trend towards worse performance. Three out of four studies found evidence that motor function remains impaired even after a time of abstinence, while no impairments in visual spatial functioning can be concluded. Functional imaging demonstrates clear differences in activation patterns between CU and controls especially in hippocampal, prefrontal and cerebellar areas. Structural differences are found in cortical areas, especially the orbitofrontal region and the hippocampus. Twenty studies (57 %) reported data on outcome effects, leading to an overall effect size of r mean = .378 (CI 95 % = [.342; .453]). Heavy use is found to be more consistently associated with effects in diverse domains than early age of onset. Questions of causality-in view of scarce longitudinal studies, especially those targeting co-occurring psychiatric disorders-are discussed.