Notes about Adrenochrome
>Anybody who's read "Fear and Loathing in Las Vegas" with their eyes open has wondered about that adrenochrome scene. What is that stuff? Where do I get that stuff? etc.
Well, adrenochrome is 3-hydroxy-1-methyl-5,6-indoline-dione – made by the oxidation of epinephrine (adrenaline). Now I can see where the hydrogens were
abstracted from, and I can generally speculate about the mechanism, but does anyone have the definitive word on electron-pushing for this little chemical anomaly?
Also, does anyone have experience with this stuff? Johnny Depp sure made it look kewl, and being the young, impressionable lad that I am, I'd sure like to know if it is "all that" or not.
Beagle
I have no experience with this compound, but of course I am very interested in it. Here are the original refs, in case anyone is willing to follow up on it. The original paper, in which Hoffer obtained "profound psychomimetic symptoms" from as little as 0.5 mg S.C. or I.V.: J. Mental Sci. 100, 29, '54
Later papers where negative results or possible slight effects were obtained by dosages up to 25mg:
Am. J. Psychiat. 111, 603, '55
Am. J. Psychiat. 115, 162, '58
Am. J. Psychiat. 116, 454, '59
Lancet ii, 308, '58
I believe that the ultimate authority of Shulgin referred to adrenochrome as "a fascinating red herring" in Tihkal. And I really hate to argue with Him. I believe that the original, positive reports were based on experiments with one mentally unstable woman. This was covered in Hoffer and Osmonds "The Hallucinogens," I believe. Other reviews are :
Hormones, Brain Function and Behavior, p181 1957.
Psychotropic Drugs p.10, 1957
Opinions that adrenochrome is not active:
Lancet, I 1287, 1960.
In Nature 191, 245, ’61 it was pointed out that adrenochrome may have significance as a hallucinogen, since it is an in vitro glutamic acid decarboxylase and cholinesterase inhibitor.
It has also been described as having a wide range of other physiological activites, as reviewed in Pharmacol. Rev. 1, 1, ’49 and Fortschr. Chem. Org.
Naturstoffe. 14, 217, ’57
Of course, most of this work was done under conditions that would be considered primitive today, and there is not absolute certainty that all research groups were working with the same compound. Originally, adrenochrome was prepared by oxidation of adrenalin with catechol oxidase or silver oxide. The chemistry of
its preparation is reviewed in Chem. Rev. 59, 181, ’59.
Additionally, adrenochrome semicarbazone has been claimed to have hallucinogenic properties similar to the parent substance: Acta Chem. Scand. 12, 1231, ’58. It certainly would be interesting to apply modern techniques to this mystery and settle it once and for all. Anyone looking for a research project?
Many thanks for the extensive foray into adrenochrome you've offered. I have a few more adrenaline oxidations I can offer. I was told epinephrine was available OTC in a veterinary context, but otherwise is available in bulk through several chemical companies. THe synthesis is a mere one-step reaction, so it looks like
the makings of a fun weekend project. Off to the library I go…
I would be glad to hear of any other epinephrine oxidations that you could offer. Also, for another fun fictionalized account of adrenochrome in the vein of H.S. Thompson, see Blood of a Wig, from the book Red Dirt Marijuana and Other Stories, by Terry Southern.
I just checked Medline, and low and behold, there has been quite a bit of work done in recent years on the physiological significance of adrenochrome.
One article that I saw on the mechanism of this transformation was Biol Signals, 5(5):275-82 1996 Sep-Oct, where it was suggested that the transformation is an enzyme mediated one, and is dependant on H2O2 and O2-. NADH also apparently
stimulates the production of adrenochrome, indicating involvement of NADH dehydrogenase.
I had no idea that this was still a current topic of research, but there were over 100 cites, just going back to 1986.
Further searching of Medline has yielded the following papers relating to adrenochrome and mental function that may prove interesting. I don't have easy access to any of them. If anyone gets them and finds anything interesting, please post.
Molecular interactions in the phenomenology of the onset of mental illness.
Chem-Biol-Interact. 1973 Jul; 7(1): 1-9
[Chemical interaction between serotonin and adrenochrome. Contribution to the
"short circuit" theory of the genesis of mental disease]
Riv-Neurol. 1971 May-Jun; 41(3): 182-7
Short circuit theory on the onset of mental illness.
Clin-Chim-Acta. 1970 Oct; 30(1): 5-11
https://erowid.org/archive/rhodium/chemistry/adrenochrome.txt