How was lithium discovered?

Lithium was discovered as a treatment for bipolar disorder by Australian physician John Cade in the mid-20th century. Dr. Cade hypothesized that a chemical buildup in the brain caused manic episodes, which could be alleviated by urinating out this chemical. During his time as a prisoner of war, he observed fluctuations in mood and energy among his fellow inmates, leading him to later experiment with urine from patients exhibiting signs of mania.

After the war, Cade began conducting experiments, injecting guinea pigs with urine from manic patients and noting that uric acid seemed to be the compound responsible for these episodes. To create a soluble form of uric acid for his injections, he used lithium to dilute the uric acid, eventually leading to the discovery that lithium alone had a calming effect on the guinea pigs. Cade then began to administer lithium to human patients, observing profound improvements in their symptoms of mania.

This discovery was groundbreaking and led to the widespread use of lithium in the treatment of mood disorders, particularly bipolar disorder, despite the initial lack of understanding of its underlying biological mechanisms. Cade's work is documented in his seminal paper, "Lithium Salts in the Treatment of Psychotic Excitement" published in 1949, which marks a pivotal moment in psychiatric treatment 1.