The extreme potency of LSD is indeed a critical part of the story; synthesizing it is difficult in part because it’s very hard to produce it in any large quantity without incidentally ingesting active doses through the air. According to Wikipedia, the threshold dose to feel effects is about 25µg. Not milligrams, like the active dose of most medicines, _micro_grams. I am sure chemists over the years have gotten accidental doses of 25µg of many tens of thousands of chemicals without ever noticing it. Albert Hoffman’s original accidental dose was consistent with a ~threshold effect, so it doesn’t seem to be especially serendipitous. He just happened to be the lucky chemist who was working with a chemical which is psychoactive in such trace amounts. (He then intentionally tested a dose of 250µg, which he thought was very small but which is in fact a solid dose.)
Also: Did Albert Hoffman hit the most powerful variant on the first try? No, he was systematically investigating similar compounds for pharmacological properties (not psychedelic properties, just regular drug discovery). LSD is just the one that had significant novel effects at low doses, and so it is the one which became famous.
Oh, that’s a really good point. Actually, it might be common for chemists to work with panels of related molecules, while in clinical trials they only work with one purified drug candidate. This makes it less likely for them to discover things by accident. Surely a piece of the puzzle!
The extreme potency of LSD is indeed a critical part of the story; synthesizing it is difficult in part because it’s very hard to produce it in any large quantity without incidentally ingesting active doses through the air. According to Wikipedia, the threshold dose to feel effects is about 25µg. Not milligrams, like the active dose of most medicines, _micro_grams. I am sure chemists over the years have gotten accidental doses of 25µg of many tens of thousands of chemicals without ever noticing it. Albert Hoffman’s original accidental dose was consistent with a ~threshold effect, so it doesn’t seem to be especially serendipitous. He just happened to be the lucky chemist who was working with a chemical which is psychoactive in such trace amounts. (He then intentionally tested a dose of 250µg, which he thought was very small but which is in fact a solid dose.)
Also: Did Albert Hoffman hit the most powerful variant on the first try? No, he was systematically investigating similar compounds for pharmacological properties (not psychedelic properties, just regular drug discovery). LSD is just the one that had significant novel effects at low doses, and so it is the one which became famous.
Oh, that’s a really good point. Actually, it might be common for chemists to work with panels of related molecules, while in clinical trials they only work with one purified drug candidate. This makes it less likely for them to discover things by accident. Surely a piece of the puzzle!