Overseas trade and European expansion in the sixteenth, seventeenth, and eighteenth centuries turned psychoactive drugs, including spirituous alcohol and tobacco, into global products. From the beginning, the commerce provoked controversy. Doctors argued about the indications, dosages, and risks of imported drugs. When use spread beyond medicine, the state became involved. Some rulers resorted to mutilation and execution to enforce prohibitions, especially against tobacco smoking. None succeeded in stamping out the novel vice or in suppressing the cultivation of tobacco, which quickly became a global crop. ‘Mankind has found too few comforts,’ wrote historian V.G. Kiernan, ‘to let itself be robbed of them.’