How Amphetamines Got Started
Nicolas Rasmussen (Professor of History and Philosophy) gives expert video advice on: What is 'amphetamine'?; How was amphetamine invented?; How did Gordon Alles introduce amphetamines to the world? and more...
What is 'amphetamine'?
Amphetamine and methamphetamine are very nearly identical molecules and they're both very closely related to adrenaline; a natural hormone that of course is stimulating and is also responsible for certain neural circuits in the brain. They were invented in pursuit of basically a synthetic adrenaline. An Adrenaline substitute for ephedrine which is also closely related to adrenaline, a natural plant drug that was popular in the late 1920's for allergies and for asthma. Because, you could take a pill to prevent you from having an asthma attack whereas before that if you had asthma you had an asthma attack you carried around an injection kit of adrenaline because that was the only thing that might save your life. Its obviously inconvenient to have an asthma attack and have to inject yourself with adrenaline and don't know what you're doing. So it was discovered that ephedrine could prevent asthma, it became a really popular drug. It was actually a shortage of it because it could only be grown in China and there was because of it's sort of trendiness and because of all these new uses and the demand, there was an incentive to come up with artificial synthetic substitutes for it, variants that may even be better.
How was amphetamine invented?
In the late 1920's there was an enterprising biochemist in California named Gordon Alles who was interested in hormones. He had been trained at the highest level in pharmacology and biochemistry of his day, but wasn't able to get an academic job, which was his great ambition at the time when he was young. The Great Depression made it hard for him to get a job. Anyway, he worked in an allergist office making pollen shots and so on. And because it was an allergist office, there was of course great interest in ephedrine. And on the side, with the approval of George Piness, which was the name of the allergist, he started synthesizing drugs that were related to adrenaline and to ephedrine. And one he discovered in 1929 is the molecule we now call amphetamine. And he took an injection of it - 50 milligrams, quite a large dose by today's standards, not huge - with a doctor friend in June 1929. And although he's looking for decongestant effects and so on, because it was an ephedrine substitute, he did immediately notice his mind was racing and so on, and his blood pressure went way up, which was a bit of an issue.
How did Gordon Alles introduce amphetamines to the world?
He first presented the results, I think at the end of 1929 with Panes at a local AMA meeting on the west coast. And just said it had certain ephedrine like effects. It could be used as a decongestant and nose drops but also had central stimulating effects. And he later learned that there was an observer in the audience from a major drug company. Anyway, he started trying to find better drugs than the amphetamines he used as an asthma remedy. He patented, he filed a patent and received a patent on the drug in 1932. And right around the time that he knew he was going to get the patent he was going to be granted, he started contacting big drug companies to find out if anyone wanted to buy his invention, to buy rights to it. Right around the time that he approached these drug companies, a product came out on the market from the drug firm Smith Kline & French that was basically a version of his invention. It was amphetamine. It wasn't the amphetamine salts that you could take as a pill, which is what Alles had patented. Because that was always his goal, a pill, because it's preferred by patients to take a pill. It was pure amphetamine base, 325 milligrams of it and very little else sealed in a metal tube that was perforated at one end, and it was a decongestant inhaler. You're supposed to take the cap off the tube and stick it in your nose and breathe the volatile amphetamine which, like adrenaline, shrinks down swollen nasal tissue. So this amphetamine inhaler was released on the market by this drug company. And this is the same drug company that, he believed anyway, had an observer at his talk in 1929. So he came to feel that they had gotten the idea from him. Anyway, a lot of negotiations. And in 1934, they agreed on a deal where Smith Kline and French would take on the rights for amphetamine salts and start overseeing its development as a medicine.
How was amphetamine introduced to the world medical market?
For me, one of the most interesting stories is how they decided what the clinical use of amphetamine was going to be. In other words, what market to target within medicine. How to make it a successful prescription drug. Then, not so different from now, drug companies had an extensive network of connections with important physicians, academic medical researchers, and they'd manage clinical trials through these experts. And the experts would receive money, and would generally involve right of veto over publication. So if a trial was unsuccessful, it made the drug look bad, you would never see a result. And this is recognized as a big problem in the medical literature today, that drug companies have too much control over clinical trials. Anyway, it wasn't perceived as a problem then. They ran it through clinical trials for all kinds of stuff. Bed wetting. Cognitive enhancement, particularly for kids who were scoring low in school. They ran it for dysmenorrhoea, painful menstruations, sort of like PMS. Obviously a very common disorder. And the experts that were most interested were psychologists and neurologists. It turned out to be good for narcolepsy. Of course ephedrine was already being used for narcolepsy. That's a condition where you fall asleep involuntarily, and so something that keeps you awake is good. It was used for certain kinds of Parkinsonism with some success. Possibly quite similar to the effects that you get with MS today. But most exciting for its commercial prospects, depression. There was an expert on depression at Harvard University Medical School and Tufts Medical School at the time named Abraham Myerson. He was a very well-recognized psychiatrist. He wrote popular best sellers. He had some unorthodox views on depression. For at least 10 years, he had been pushing a new view of depression that it was fundamentally rooted in the lack of pleasure, lack of pursuit of pleasure, anhedonia. And when he tried amphetamine on patients, and seeing depression through this lens of anhedonia, he saw it as a miracle drug. It made people pursue pleasure more. It made them more lively and interested in the world around them.
Which diseases were first treated with amphetamines in 1937?
In 1937, towards the end of the year I think, the drug was approved by the American Medical Association for it's first three clinical uses, and that they were all psychiatric. Post-encephalitis parkinson is a particular Parkinsons disease, Narcolepsy, and depression. And later some more uses were approved. In those days approval meant that they simply had a right to advertise them in certain high profile journals. There was no FDA regulation on that kind of thing in place.