Perhaps the most dreaded side effect in all of psychiatry is the MAOI-cheese interaction. We now understand its mechanism fairly well, namely, that most cheeses contain high amounts of the amino acid tyramine, which has the effect of increasing the release of norepinephrine (NE) from nerve terminals. Normally, this excess NE is metabolized by the enzyme monoamine oxidase (MAO), but in the presence of MAO inhibitors, NE levels rise dangerously, leading to hypertension and, rarely, hemorrhagic strokes. But in the early 1960s, nobody had an inkling of these dangers. It took a psychiatric resident to save the day. Barry Blackwell, who was training at Maudsley Hospital in London at the time, began reading about sporadic cases of subarachnoid hemmorhages in patients who were taking MAOIs; some of these patients also had high blood pressure. A pharmacist told Blackwell about his wife, who was on an MAOI and had developed hypertension and headache after eating cheese. Intrigued, Blackwell and a colleague experimented on themselves: they took Parnate for a week, then gorged on cheese! They felt perfectly fine. Nonetheless, Blackwell noted several cases in his hospital of patients on MAOIs eating cheese sandwiches and developing hypertensive headaches, and he published his suspicions in the Lancet. It took some time before a skeptical medical community took this cheese connection seriously, however, partly because there was no known mechanism to explain it.

Source: Healy D. The Anti-Depressant Era. Harvard University Press, 1997.