All starting compounds for ergot drugs, lysergic acids being the most critical, could solely be generated by cultivating sclerotia on rye. In 1960 and 1964, Italian project teams led by the German-British chemist Ernst Boris Chain and the natural products research group at Sandoz AG in Basel accomplished a breakthrough in the submers cultivation production of lysergic acid-related compounds in bioreactors. In the USA, the German chemist Heinz Floss resolved the biosyntheses of lysergic acid and further ergotalkaloids by feeding radioactively labelled building blocks to liquid cultures of ergot. In 1999 the research teams of Paul Tudzynski (University of Munster) and Ullrich Keller (TU Berlin) identified the complete gene cluster in the ergot genome encoding the enzymes of the ergotamine biosynthesis and orchestrating the enzymatic steps to ergotamine. Today, ergotoxicosis of man still occurs sporadically in developing countries, where suitable measures for the reduction of sclerotia in the harvest and the continuous monitoring of cereals for toxin control cannot be constantly upheld. The gangrenous ergotism generated by contaminated forage grasses is still a worldwide problem for agricultural farms and nurseries. The receptors by which ergotalkaloids convey the gangrenous toxicosis are now well understood. The striking similarity between the symptoms of convulsive ergotism and the drug-induced "Serotonin-Syndrom", as shown by the Australian neurologist Mervyn J. Eadie, reveals a passable analogical conclusion as to which receptor types may be involved in causing this kind of ergotoxicosis. In 2022, the US-American pharmacologist Bryan Roth elucidated the binding of LSD to the 5-HT2A/2B-receptors by applying the novel cryo electron microscopy technology. Leveraging the new high resolution structural data, the Chinese researcher Sheng Wang designed molecules showing antidepressive activity in a mouse model without displaying a hallucinogenic effect. Currently LSD is part of psychiatric clinical research studies to assess its therapeutic benefit in the therapy of difficult to treat depressions, traumatic disorders, anxiety states or cluster headache.
