Essentials: The Science & Treatment of Bipolar Disorder

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Lithium Discovery, Dr. John Cade, Uric Acid

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The discovery of lithium is one of psychiatry's most gripping origin stories, and Huberman tells it with relish. Dr. John Cade, an Australian psychiatrist, survived Japanese captivity from the fall of Singapore in 1942 until 1945. During that time, he observed fellow prisoners cycling through wild mood vacillations and formed a bold hypothesis: something in their brains was building up and being urinated out. After his release, Cade began injecting guinea pigs with urine from manic and non-manic patients, finding that manic-patient urine was more toxic. He narrowed the culprit to uric acid — and then, trying to dilute it for injection, discovered that lithium was the only compound that worked as a solvent. What he had inadvertently created was lithium urate, which had a pronounced calming effect on the animals. The real breakthrough came when he ran proper controls: lithium alone, injected into guinea pigs, calmed them down. From there — in the more permissive medical culture of the 1940s — Cade moved directly to human patients, finding profound anti-manic effects. His paper, 'Lithium Salts in the Treatment of Psychotic Excitement,' was published September 3, 1949 in the Medical Journal of Australia.