adrenochrome

The oxidation reaction that converts adrenaline into adrenochrome occurs both in vivo and in vitro. Silver oxide (Ag₂O) was among the first reagents employed for this,{{cite journal |last1=Veer |first1=W. L. C. |title=Melanin and its precursors II. On adrenochrome |journal=Recueil des Travaux Chimiques des Pays-Bas |date=1942 |volume=61 |issue=9 |pages=638–646 |doi=10.1002/recl.19420610904}} but a variety of other oxidizing agents have been used successfully.{{cite journal |last1=Heacock |first1=R. A. |title=The Chemistry Of Adrenochrome And Related Compounds |journal=Chemical Reviews |date=1 April 1959 |volume=59 |issue=2 |pages=181–237 |doi=10.1021/cr50026a001 |url=https://chemistry.mdma.ch/hiveboard/rhodium/pdf/adrenochrome.review.pdf}} In solution, adrenochrome is pink and further oxidation of the compound causes it to polymerize into brown or black melanin compounds.

Adrenochrome is readily synthesized from commercially available reagents: chloroacetic acid and catechol react in the presence of phosphoryl chloride to yield chloroacetylcatechol. After purification, chloroacetylcatechol is reacted with aqueous methylamine and treated with hydrochloric acid, yielding adrenalone hydrochloride. This is then hydrogenated to racemic adrenaline. Finally, adrenaline is oxidized to adrenochrome by an appropriate oxidizing agent such as silver oxide.{{cite journal|url=https://pubs.acs.org/doi/10.1021/ja01129a531|title=Synthesis of dl-Adrenalin-β-C14 and dl-Adrenochrome-β-C14|publisher=ACS Publications|author=Schayer, Richard W.|journal=Journal of the American Chemical Society |language=en-US|url-status=live|date=1952|volume=74 |issue=9 |page=2441 |doi=10.1021/ja01129a531 |bibcode=1952JAChS..74.2441S |access-date=October 25, 2022|archivedate=October 25, 2022|archiveurl=https://archive.today/20221025141335/https://pubs.acs.org/doi/10.1021/ja01129a531|url-access=subscription}}

File:Adrenochrome.jpg

Several small-scale studies involving 15 or fewer test subjects conducted in the 1950s and 1960s reported that adrenochrome triggered psychotic reactions such as thought disorder and derealization.{{cite journal | last1 = Smythies | first1 = John | author-link1 = John Raymond Smythies | s2cid = 37594882 | title = The adrenochrome hypothesis of schizophrenia revisited | journal = Neurotoxicity Research | volume = 4 | issue = 2 | pages = 147–150 | date = January 2002 | pmid = 12829415 | doi = 10.1080/10298420290015827 | citeseerx = 10.1.1.688.3796 | issn = 1029-8428 | eissn = 1476-3524 | oclc = 50166444 }}

In 1954, researchers Abram Hoffer and Humphry Osmond claimed that adrenochrome is a neurotoxic, psychotomimetic substance and may play a role in schizophrenia and other mental illnesses.{{cite journal | last1 = Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | first3 = John | last3 = Smythies| author-link3 = John Raymond Smythies | title = Schizophrenia: A New Approach. II. Result of a Year's Research | journal = The Journal of Mental Science | volume = 100 | issue = 418 | pages = 29–45 | date = January 1954 | pmid = 13152519 | doi = 10.1192/bjp.100.418.29 | eissn = 1472-1465 | issn = 0007-1250 | lccn = 89649366 | oclc = 1537306 | s2cid = 42531852 | df = dmy-all }} In what Hoffer called the "adrenochrome hypothesis",{{cite journal | last1 = Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | title = The Adrenochrome Hypothesis and Psychiatry | url = http://www.orthomolecular.org/library/jom/1999/articles/1999-v14n01-p049.shtml | access-date = 2024-03-15 | journal = The Journal of Orthomolecular Medicine | volume = 14 | issue = 1 | date = First Quarter 1999 | pages = 49–62 | archive-url = https://web.archive.org/web/20240220043758/http://www.orthomolecular.org/library/jom/1999/articles/1999-v14n01-p049.shtml | archive-date = 2024-02-20 | url-status = live | issn = 0834-4825 | oclc = 15726974 | s2cid = 41468628 | df = dmy-all}} he and Osmond in 1967 speculated that megadoses of vitamin C and niacin could cure schizophrenia by reducing brain adrenochrome.{{cite book | author1=Abram Hoffer | author2=Humphrey Osmond | title=The Hallucinogens | publisher=Elsevier | date=1967 | isbn=978-1-4832-3296-6 | doi=10.1016/c2013-0-12543-3 | lccn=66030086 | oclc=332437 | ol=OL35255701M | url=https://bitnest.netfirms.com/external/Books/TheHallucinogens | pages=272–273}}{{cite journal | vauthors = Hoffer A | date = 1994 | title = Schizophrenia: An Evolutionary Defense Against Severe Stress | journal = Journal of Orthomolecular Medicine | volume = 9 | issue = 4 | pages = 205–2221 | url = http://orthomolecular.org/library/jom/1994/pdf/1994-v09n04-p205.pdf }}

The treatment of schizophrenia with such potent anti-oxidants is controversial. In 1973, the American Psychiatric Association reported methodological flaws in Hoffer's work on niacin as a schizophrenia treatment and referred to follow-up studies that did not confirm any benefits of the treatment.{{cite web | vauthors = Lipton MA, Ban TA, Kane FJ, Levine J, Mosher LR, Wittenborn R | title = Task Force Report on Megavitamin and Orthomolecular Therapy in Psychiatry | publisher = American Psychiatric Association | year = 1973 | url = https://www.old.quackwatch.org/01QuackeryRelatedTopics/apa_megavitamin.pdf | access-date = 7 September 2020 | archive-date = 23 February 2021 | archive-url = https://web.archive.org/web/20210223194022/https://www.old.quackwatch.org/01QuackeryRelatedTopics/apa_megavitamin.pdf | url-status = dead }} Multiple additional studies in the United States,{{cite journal | doi = 10.1001/archpsyc.1973.01750330010002 |vauthors=Wittenborn JR, Weber ES, Brown M | title = Niacin in the Long-Term Treatment of Schizophrenia | journal = Archives of General Psychiatry | year = 1973 | volume = 28 | issue = 3 | pages = 308–315 | pmid = 4569673 | url = http://archpsyc.ama-assn.org/cgi/content/abstract/28/3/308| url-access = subscription }} Canada,{{cite journal | vauthors = Ban TA, Lehmann HE | title = Nicotinic Acid in the Treatment of Schizophrenia: A Summary Report | journal = Schizophrenia Bulletin | year = 1970 | volume = 1 | issue = 3 | pages = 5–7 | doi = 10.1093/schbul/1.3.5 | doi-access = free }} and Australia{{cite journal |vauthors=Vaughan K, McConaghy N | s2cid = 38857700 | title = Megavitamin and dietary treatment in schizophrenia: a randomised, controlled trial | journal = Australian and New Zealand Journal of Psychiatry | year = 1999 | volume = 33 | issue = 1 | pages = 84–88 | pmid = 10197889 | doi =10.1046/j.1440-1614.1999.00527.x}} similarly failed to find benefits of megavitamin therapy to treat schizophrenia.

The adrenochrome theory of schizophrenia waned, despite some evidence that it may be psychotomimetic, as adrenochrome was not detectable in people with schizophrenia.{{citation needed|date=March 2021}}

In the early 2000s, interest was renewed by the discovery that adrenochrome may be produced normally as an intermediate in the formation of neuromelanin. This finding may be significant because adrenochrome is detoxified at least partially by glutathione-S-transferase. Some studies have found genetic defects in the gene for this enzyme.{{cite book | vauthors = Smythies J | veditors = Smythies J |title=Disorders of Synaptic Plasticity and Schizophrenia |date=2004 |publisher=Elsevier Academic Press |isbn=978-0-12-366860-8 |pages=xv |edition=1st}}

Adrenochrome is also believed to have cardiotoxic properties.{{cite journal |last1=Bindoli |first1=Alberto |last2=Rigobello |first2=Maria Pia |last3=Galzigna |first3=Lauro |title=Toxicity of aminochromes |journal=Toxicology Letters |date=July 1989 |volume=48 |issue=1 |pages=3–20 |doi=10.1016/0378-4274(89)90180-X|pmid=2665188 |hdl=11577/2475305 |hdl-access=free }}{{cite journal |last1=Behonick |first1=George S. |last2=Novak |first2=Mark J. |last3=Nealley |first3=Eric W. |last4=Baskin |first4=Steven I. |title=Toxicology update: the cardiotoxicity of the oxidative stress metabolites of catecholamines (aminochromes) |journal=Journal of Applied Toxicology |date=December 2001 |volume=21 |issue=S1 |pages=S15–S22 |doi=10.1002/jat.793|pmid=11920915 |s2cid=27865845 }}

• In his 1954 book The Doors of Perception, Aldous Huxley mentioned the discovery and the alleged effects of adrenochrome, which he likened to the symptoms of mescaline intoxication, although he had never consumed it.
• Anthony Burgess mentions adrenochrome as "drencrom" at the beginning of his 1962 novel A Clockwork Orange. The protagonist and his friends are drinking drug-laced milk: "They had no license for selling liquor, but there was no law yet against prodding some of the new veshches which they used to put into the old moloko, so you could peet it with vellocet or synthemesc or drencrom or one or two other veshches [...]"
• Hunter S. Thompson mentioned adrenochrome in his 1971 book Fear and Loathing in Las Vegas.{{cite magazine | last=Friedberg | first=Brian | title=The Dark Virality of a Hollywood Blood-Harvesting Conspiracy | magazine=Wired | url=https://www.wired.com/story/opinion-the-dark-virality-of-a-hollywood-blood-harvesting-conspiracy/ | access-date=21 February 2021}} This is the likely origin of current myths surrounding this compound, because a character states that "There's only one source for this stuff{{nbsp}}... the adrenaline glands from a living human body. It's no good if you get it out of a corpse." The adrenochrome scene also appears in the novel's film adaptation.{{cite news |last1=Adams |first1=Josie |title=The truth about adrenochrome |url=https://thespinoff.co.nz/society/07-04-2020/explainer-adrenochrome-the-drug-that-doesnt-exist/ |access-date=28 June 2020 |work=The Spinoff |date=7 April 2020}} In the DVD commentary, director Terry Gilliam admits that his and Thompson's portrayal is a fictional exaggeration. Gilliam insists that the drug is entirely fictional and seems unaware of the existence of a substance with the same name. Hunter S. Thompson also mentions adrenochrome in his book Fear and Loathing on the Campaign Trail '72. In the footnotes in chapter April, page 140, he says: "It was sometime after midnight in a ratty hotel room and my memory of the conversation is hazy, due to massive ingestion of booze, fatback, and forty cc's of adrenochrome."
• In the first episode of the ITV series Lewis, "Whom the Gods Would Destroy", the motive for the crimes was that a prostitute had been killed years previously to harvest her adrenal glands.
• Adrenochrome is mentioned in the 2014 Warhammer 40,000 novel The Talon of Horus by Aaron Dembski-Bowden. It is described as a clear liquid beverage that is, "harvested from the adrenal glands of living slaves [...]"
• Adrenochrome is the subject of several conspiracy theories, including QAnon and Pizzagate,{{cite web|title=Fear and adrenochrome|url=https://spectator.us/fear-adrenochrome-conspiracy-theory-drug/|date=4 May 2020|website=Spectator USA|language=en-US|access-date=23 May 2020|archive-date=20 September 2020|archive-url=https://web.archive.org/web/20200920020254/https://spectator.us/fear-adrenochrome-conspiracy-theory-drug/|url-status=dead}}{{cite web|title=How Facebook connects 'pizzagate' conspiracy theorists|url=https://www.nbcnews.com/tech/social-media/fire-pizzagate-shop-reignites-conspiracy-theorists-who-find-home-facebook-n965956|website=NBC News|date=February 2019 |language=en|access-date=23 May 2020}}{{Skeptoid | id=4750 | number=750 | title=How to Extract Adrenochrome from Children | date=20 October 2020 | access-date=20 October 2020}} in which the chemical plays a similar role to earlier blood libel and Satanic ritual abuse stories.{{cite magazine |last1=Kantrowitz |first1=Lia |title=QAnon, Blood Libel, and the Satanic Panic |url=https://newrepublic.com/article/159529/qanon-blood-libel-satanic-panic |magazine=The New Republic |access-date=8 May 2021 |date=29 September 2020}} The theories commonly state that a cabal of Satanists rape and murder children, and harvest adrenochrome from their victims' blood as a drug{{cite magazine|last1=Friedberg |first1=Brian |title=The Dark Virality of a Hollywood Blood-Harvesting Conspiracy |url=https://www.wired.com/story/opinion-the-dark-virality-of-a-hollywood-blood-harvesting-conspiracy/ |access-date=February 16, 2022|magazine=Wired|date=July 31, 2020}}{{cite news |last1=Hitt|first1=Tarpley|title=How QAnon Became Obsessed With 'Adrenochrome,' an Imaginary Drug Hollywood Is 'Harvesting' from Kids |url=https://www.thedailybeast.com/how-qanon-became-obsessed-with-adrenochrome-an-imaginary-drug-hollywood-is-harvesting-from-kids |newspaper=The Daily Beast |access-date=27 January 2021 |date=August 14, 2020}} or as an elixir of youth.{{cite news |date= January 21, 2021|title=QAnon: A Glossary |work=Anti-Defamation League|url=https://www.adl.org/blog/qanon-a-glossary|access-date=February 15, 2022}} In reality, adrenochrome has been produced by organic synthesis since at least 1952,{{cite web|url=https://patents.google.com/patent/US3445478A/en|title=Method of synthesizing adrenochrome monoaminoguanidine|publisher=Google Patents|language=en-US|url-status=live|date=1965|access-date=October 25, 2022|archivedate=October 16, 2021|archiveurl=https://web.archive.org/web/20211016150832/https://patents.google.com/patent/US3445478A/en}} is synthesized by biotechnology companies for research purposes, and has no medical or recreational uses.{{cite web|url=https://science.howstuffworks.com/adrenochrome.htm|title=Untangling the Medical Misinformation Around Adrenochrome|author=Walker-Journey, Jennifer|publisher=HowStuffWorks|language=en-US|url-status=live|date=April 14, 2021|access-date=October 25, 2022|archivedate=April 14, 2021|archiveurl=https://web.archive.org/web/20210414211128/https://science.howstuffworks.com/adrenochrome.htm}}

• Adrenolutin

{{reflist}}

• [http://www.erowid.org/chemicals/adrenochrome/adrenochrome_info1.shtml Adrenochrome Commentary] at erowid.org
• [https://web.archive.org/web/20090111090507/http://webeye.ophth.uiowa.edu/eyeforum/atlassearch1.htm?ComparisonType1_1=LIKE&Value1_1=adrenochrome&FieldName1=Diagnosis&NumCriteriaDetails1=1&PageID=2&GlobalOperator=AND&NumCriteria=1 Adrenochrome deposits] resulting from the use of epinephrine-containing eye drops used to treat glaucoma from the [https://web.archive.org/web/20050303205443/http://webeye.ophth.uiowa.edu/eyeforum/atlassearch1.htm Iowa Eye Atlas] (searched for diagnosis = adrenochrome)
• [https://www.mcgill.ca/oss/article/pseudoscience/qanons-adrenochrome-quackery QAnon’s Adrenochrome Quackery], Joe Schwarcz, 10 Feb 2022, Office for Science and Society, McGill University

{{Hallucinogens}}

{{Phenethylamines}}

Category:Biology controversies

Category:Hallucinogens

Category:Indolequinones

Category:Phenethylamines

Category:Psychiatry controversies

Category:QAnon

Category:Secondary alcohols