The article argues that medical responses to plague were a cause of the ‘psychoactive revolution’ during the long seventeenth century. Focusing on four metropoles in the Baltic and North Sea region, it shows that the commodification of sugar, opiates and tobacco during the last century of the Second Great Pandemic correlates both with outbreaks of plague in Amsterdam, Hamburg, London and Stockholm and with the intra-regional prescription of these intoxicants in popular and authorized plague physic. In so doing, it argues for the importance of household consumption practices in driving the psychoactive revolution and points to the importance of women as well as men in the popularization of intoxicants. By tracing the popularization of sugar, tobacco and opium from c.1600 rather than c.1800 and considering their dietary uptake in relation to material changes in plague physic, it identifies an under-appreciated set of consumer motives informing household consumption practices: not least the need to allay fear, pain and bodily and mental disorder. The article concludes by introducing the concept of ‘accustomization’ as the way in which contemporary observers explained how reactive consumption in the face of epidemics could become habitual, recreational and forms of dependency over time.