Editing Niacin (section)

==In schizophrenia==
In 1954, researchers [[Abram Hoffer]] and [[Humphry Osmond]] claimed that [[adrenochrome]], a chemical compound produced by the oxidation of adrenaline (epinephrine), 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="hallucinogens">{{cite book | last1 =  Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | date = 1968-01-01 | title = The Hallucinogens | url = https://archive.org/details/hallucinogens0000hoff/ | url-access = registration | language = en | edition = First | publisher = [[Academic Press]] | isbn = 978-0123518507 | lccn = 66030086 | oclc = 332437 | ol = OL35255701M | access-date = 2024-03-15 | via = [[Internet Archive]] | quote= | quote-page= | quote-pages= | df = dmy-all}}</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>  He tested this in small numbers of patients and claimed that it was frequently impressively successful.

The treatment of schizophrenia with such potent anti-oxidants is highly contested. 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]].  Hoffer, in a lengthy review article, replied that the follow-up studies were poorly designed, using incorrect doses and illogical measures of whether the patients had recovered or not, and voiced suspicions that they had been deliberately set up to make the niacin protocol look bad by doctors who had spoken publicly in support of the use of tranquillizers and wanted to make it look as if they were right.

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>{{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>  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>