Addictions to cocaine and other stimulant 'designer' drugs remain unaided by pharmacotherapies. Several decades of work support the use of agents that augment neurochemistry (e.g., dopamine and glutamate transmission) to normalize reward- and mood-governing pathways that become dysregulated following chronic stimulant use. An unexplored but promising route is to test clinically-available antibiotics in models of mood and addiction to holistically evaluate their therapeutic potential.