Editing Adrenochrome (section)

== History ==
[[File:Adrenochrome.jpg|thumb|left|An adrenochrome ampoule]]

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]].<ref name=Smythies>{{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 }}</ref>

In 1954, researchers [[Abram Hoffer]] and [[Humphry Osmond]] claimed that adrenochrome is a [[neurotoxin|neurotoxic]], [[psychotomimetic]] substance and may play a role in [[schizophrenia]] and other mental illnesses.<ref name="pmid13152519">{{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 = [[British Journal of Psychiatry|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 }}</ref> In what Hoffer called the "adrenochrome hypothesis",<ref name="Hoffer2">{{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}}</ref> he and Osmond in 1967 speculated that [[Megavitamin therapy|megadoses]] of [[vitamin C]] and [[niacin (nutrient)|niacin]] could cure schizophrenia by reducing brain adrenochrome.<ref name="HofferOsmond1967">{{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}}</ref><ref name=hoffer94>{{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 }}</ref>

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.<ref name="APA">{{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 }}</ref> Multiple additional studies in the United States,<ref name="ArchGenPsy">{{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}}</ref> Canada,<ref name="SZ Bull">{{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 }}</ref> and Australia<ref name="ANZJP">{{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}}</ref> similarly failed to find benefits of megavitamin therapy to treat [[History of schizophrenia|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]].<ref name=Smythies /> 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.<ref>{{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}}</ref>

Adrenochrome is also believed to have [[Cardiotoxicity|cardiotoxic]] properties.<ref>{{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 }}</ref><ref>{{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 }}</ref>