The Molecule That Nearly Became LSD - Silenced by Nausea
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The Molecule That Nearly Became LSD - Silenced by Nausea
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In this episode, we tell the story of quipazine from its 1966 discovery through human trials and animal experiments, tracing why it was classified as antidepressant-like and then abandoned - and asking whether the nausea problem closed a door science has not yet reopened.
Person: anonymous human volunteers
Date: 1966 (first description)
Compound: quipazine (one-2-quinolinyl-piperazine; “two-QP”)
Dose: 25 mg oral caused significant gastrointestinal distress
Receptor profile: potent 5-HT3 agonist; agonist at 5-HT2A/2B/2C; inhibits serotonin reuptake
- Quipazine was first described in 1966 and later labeled antidepressant-like by 1971.
- Oral doses of 25 mg in humans produced significant nausea, vomiting, cramping, flatulence and diarrhea.
- Quipazine is a 1-(2-quinolinyl)-piperazine (also called two-QP) synthesized from 2-chloroquinoline and piperazine.
- In rodents and monkeys quipazine produced the head-twitch response characteristic of classical psychedelics.
- In drug discrimination studies, rats fully substituted quipazine for LSD, indicating indistinguishable drug-state effects in that model.
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