Editing John Cade (section)

==Discovery of the effect of lithium on mania==
After the war, Cade recuperated very briefly in Heidelberg Hospital, then took up a position at Bundoora Repatriation Mental Hospital in Melbourne.<ref>On Bundoora hospital, see the summaries by [https://www.findingrecords.dhhs.vic.gov.au/CollectionResultsPage/MontParkHospital the Victorian Department of Health and Human Services] and by [https://researchdata.edu.au/bundoora-repatriation-hospital-1933-1993/933242 Research Data Australia].</ref> It was at an unused pantry in Bundoora that he conducted crude experiments which led to the discovery of lithium as a treatment of bipolar disorder. Since he had no sophisticated analytical equipment these experiments mostly consisted of injecting urine from mentally ill patients into the abdomen of [[guinea pig]]s. His early experiments suggested to him that the urine from manic patients was more toxic. There are 2 toxic substances in urine: urea and uric acid. He found urea was the same in both ill and healthy people. He started to work on uric acid. In order to do that, he made artificial solutions of uric acid. To make up different strengths of uric acid he needed to convert it into a substance that he could more easily manipulate. On its own uric acid would not dissolve in water. Then, in an effort to increase the water solubility of uric acid, lithium was added to make a solution of lithium urate.  Cade found that in the guinea pigs injected with lithium carbonate solution, as a control solution, the guinea pigs were more restful.<ref name="mja">{{cite journal|last=Cade|first=John FJ|author-link=John Cade|date=3 September 1949|title=Lithium salts in the treatment of psychotic excitement|journal=Medical Journal of Australia|volume=2|issue=36|pages=349–352|doi=10.1080/j.1440-1614.1999.06241.x|pmid=10885180|pmc=2560740}}</ref> His use of careful controls in his experiments revealed that the lithium-ion had a calming effect by itself, but even this finding may have been caused by the toxic effects of an excessive dose of lithium.  After ingesting lithium himself to ensure its safety in humans,<ref name=jack/> Cade began a small-scale trial of lithium citrate and/or lithium carbonate on some of his patients diagnosed with [[mania]], [[schizophrenia|dementia præcox]] or [[melancholia]], with outstanding results.  The calming effect was so robust that Cade speculated that mania was caused by a deficiency in lithium.<ref name=mja/> He published these findings in the [[Medical Journal of Australia]] in a paper entitled 'Lithium salts in the treatment of psychotic excitement', published in 1949.<ref>{{Cite journal|last=Cade|first=J. F.|date=2000|title=Lithium salts in the treatment of psychotic excitement. 1949.|journal=Bulletin of the World Health Organization|volume=78|issue=4|pages=518–520|issn=0042-9686|pmc=2560740|pmid=10885180}}</ref>

While Cade's results appeared highly promising, side effects of lithium in some cases led to non-compliance.  The [[lithium toxicity|toxicity of lithium]] led to several deaths of patients undergoing lithium treatment. The problem of toxicity was greatly reduced when suitable tests were developed to measure the lithium level in the blood.  Moreover, as a naturally occurring chemical, lithium salt could not be [[patent]]ed, meaning that its manufacturing and sales were not considered commercially viable. These factors prevented its widespread adoption in psychiatry for some years, particularly in the United States, where its use was banned until 1970.<ref>{{cite journal | doi=10.1111/j.1399-5618.2009.00706.x | title=The history of lithium therapy | date=2009 | last1=Shorter | first1=Edward | journal=Bipolar Disorders | volume=11 | issue=Suppl 2 | pages=4–9 | pmid=19538681 | pmc=3712976 }}</ref>