0.5 mg "sic" vs 400 mg aspirin; compound unnamed; human stakes: potential psychedelic/antidepressant but unconfirmed
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0.5 mg "sic" vs 400 mg aspirin; compound unnamed; human stakes: potential psychedelic/antidepressant but unconfirmed
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A single line in a paper flagged with a Latin mark calls out an impossible dose: half a milligram - one-eightieth the weight of an aspirin - and that unexplained number has haunted six decades of research into a drug that made rodents act like they'd taken LSD. How did a molecule that produced clear psychedelic-like effects in animals, yet caused uncontrollable vomiting and produced no psychedelic reports in humans at 25 mg, remain a pharmacological ghost in the literature?
In this episode, we trace the molecule’s arc from its first synthesis in 1966 through animal studies, receptor mapping, and the sparse human data, and we ask what stalled its path to clinical clarity - is the answer buried in an embargoed doctoral thesis or in the messy biology of serotonin receptors?
Person: quipazine
Date: first reported 1966
Event: registered head-twitch response in rodents by 1977
Dose reported in human volunteers: 25 mg orally with nausea and no LSD-like effects
Embargoed record: doctoral thesis at Columbia University embargoed until 2030
- The paper lists a dose of 0.5 mg, annotated with a Latin mark indicating doubt.
- Quipazine was first synthesized and reported in 1966.
- By 1977, quipazine produced the head-twitch response in rodents, a marker of 5-HT2A activation.
- Human volunteers given 25 mg orally reported nausea, flatulence, gastrointestinal discomfort, and diarrhea with no psychedelic subjective effects.
- A 1994 theoretical proposal suggested an anti-nausea drug could enable human testing, but the proposed test appears only in an anonymous, unverified report and a Columbia thesis embargoed until 2030.
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