Lithium is as puzzling as it is potent. It was the first drug used to treat mental illness, and more than 50 years later, it is still one of the most widely used psychiatric medications. But the doctors who prescribe lithium to their patients still do not know how it works or even why it works. “It is the most mysterious drug in psychiatry,” says De-Maw Chuang, a biologist at the National Institute of Mental Health. “It’s so small, but it is so powerful.”
Unlike other psychoactive chemicals—large, complex molecules like Prozac (fluoxetine) or Abilify (aripiprazole)—lithium is extremely simple. It is an element, the lightest of the metals, and its chemical properties are similar to those of the sodium in table salt. Nonetheless, researchers have recently found that lithium could be something close to a psychiatric wonder drug. It has two remarkable powers in the brains of mentally ill patients: protecting neurons from damage and death and alleviating existing damage by spurring new nerve cell growth. Far beyond its current application as a mood stabilizer, lithium could be helpful in treating or preventing Alzheimer’s disease, schizophrenia, stroke, glaucoma, Lou Gehrig’s disease (amyotrophic lateral sclerosis), and Huntington’s disease—an impressive tally that earned it the nickname “the aspirin of the brain” in the journal Nature.
The mood-stabilizing powers of lithium were discovered by accident in the 1940s by John F. J. Cade, a lone psychiatrist working in Melbourne, Australia. Cade had noticed that some substance in the urine of patients with mania was particularly toxic and was investigating uric acid as the potential culprit. He added lithium to the uric acid so it would dissolve more easily in water and injected it into mice. The lithium appeared to have a protective effect against the uric acid. Cade also noticed that the injections made the animals extremely lethargic and unresponsive. That response made him wonder: Might lithium also neutralize his patients’ mania?
