Lithium came out of a guinea-pig experiment
John Cade published lithium for mania in 1949, after an animal experiment aimed at something else entirely. How lithium works is still not settled.
We have not finished checking this source. No judgement either way. how we score evidence
Caveat on this rating: The serendipity is real and it is commonly overstated, so this row states both. Cade had a hypothesis - a toxin in manic urine - and used lithium urate because uric acid dissolves poorly; he then tested lithium carbonate alone, which is how the lithium rather than the urate was identified as active. Lopez-Munoz et al. 2018 (Int J Mol Sci 19:2143, doi 10.3390/ijms19072143) gives the balanced reading: chance played an important role, within a deliberately designed series. The modern claim that Cade's guinea pigs were simply lithium-toxic is NOT asserted here: no source for it was located, and an unsourced debunk is the same error in the other direction. A free reprint of the 1949 paper is at PMC2560740 (Bull World Health Organ 2000;78:518-520).
Lithium reached psychiatry in 1949 through an animal experiment aimed at something else. How it works is still an open question.
Significant findings
John Cade, an Australian psychiatrist, suspected a toxin in the urine of manic patients. He injected guinea pigs to look for it, and used a lithium salt mainly because it dissolved well.
The animals became placid. Cade then tested lithium on its own, which is how he showed the lithium was doing the work.
1949. The first modern psychiatric drug.
Calling this pure luck is unfair to him. The hypothesis was his and the follow-up was deliberate; the answer simply came from a direction he had not planned.
What has never arrived is the explanation. Today, how lithium works remains unsettled.
Worth asking
Lithium is the clean reminder that "we do not know why it works" and "it works" are different sentences.
If you take it, ask what blood levels and monitoring your prescriber wants. Never change a lithium dose on your own.
Source
Lithium Salts in the Treatment of Psychotic Excitement — Cade JFJ (1949)
Read the source: https://doi.org/10.5694/j.1326-5377.1949.tb36912.x
DOI: 10.5694/j.1326-5377.1949.tb36912.x
How this was scored
- Study design
- not recorded
- Funding
- not recorded
- Published in
- not recorded
- Sample size
- not recorded
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
We have not finished checking this source, so there is no scoring to show yet. “We have not checked this yet” and “this is disputed” are different statements, so no scored band is shown rather than a low one.
Read the full scoring rubric, including what it can't tell you.
Published August 31, 2026.
Questions
How strong is the evidence behind this?
Resolv rates this source "not yet assessed". We have not finished checking this source. No judgement either way. One caveat travels with that badge: The serendipity is real and it is commonly overstated, so this row states both. Cade had a hypothesis - a toxin in manic urine - and used lithium urate because uric acid dissolves poorly; he then tested lithium carbonate alone, which is how the lithium rather than the urate was identified as active. Lopez-Munoz et al. 2018 (Int J Mol Sci 19:2143, doi 10.3390/ijms19072143) gives the balanced reading: chance played an important role, within a deliberately designed series. The modern claim that Cade's guinea pigs were simply lithium-toxic is NOT asserted here: no source for it was located, and an unsourced debunk is the same error in the other direction. A free reprint of the 1949 paper is at PMC2560740 (Bull World Health Organ 2000;78:518-520). The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Lithium Salts in the Treatment of Psychotic Excitement — Cade JFJ (1949). DOI: 10.5694/j.1326-5377.1949.tb36912.x. The full source is linked on this page so you can read it yourself.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.