Between 1085 and 1927, epidemics of "convulsive
ergotism" were widespread east of the Rhine in Europe due to consumption of grain contaminated with ergot, which is produced by the fungus Claviceps purpurea. West of the Rhine, consumption of ergot-contaminated food caused epidemics of gangrenous
ergotism. The clinical features of convulsive
ergotism--muscle twitching and
spasms, changes in mental state,
hallucinations, sweating, and
fever lasting for several weeks--suggest serotonergic overstimulation of the CNS (ie, the
serotonin syndrome). The
ergot alkaloids are
serotonin agonists.
Dihydroergotamine binds to
serotonin receptors in the dorsal horn of the spinal cord, which is the site of neuropathological changes in convulsive
ergotism.
Dihydroergotamine given to human beings can cause the
serotonin syndrome. Ergots produced by different strains of Claviceps purpurea, and those growing in different
soils, may have different ergot
alkaloid compositions. An
alkaloid, present in high concentrations in ergots from east of the Rhine, may have caused convulsive
ergotism at a circulating concentration insufficient to produce peripheral ischaemia. The
serotonin syndrome may, therefore, have been a public-health problem long before it was recognised as a complication of modern psychopharmacology.