Growing interest has been seen in using lysergic acid diethylamide (LSD) in psychiatric research and therapy. However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well-defined doses of LSD. Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic with a broad history of early psychiatric research and recreational use [1, 2]. LSD induces a range of complex alterations of the mind that have been shown to depend on serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor stimulation. LSD showed dose-proportional pharmacokinetics and first-order elimination and dose-dependently induced subjective responses starting at the 25 µg dose. The LSD dose–response curve showed a ceiling effect for subjective good effects, and ego dissolution and anxiety increased further at a dose above 100 µg. These results may assist with dose finding for future LSD research. The full psychedelic effects of LSD are primarily mediated by serotonin 5-HT2A receptor activation.
We characterized the effects of LSD at different doses to support the dosing of LSD for research and LSD-assisted therapy. LSD exhibited dose-proportional PKs and first-order elimination. It produced significant dose-dependent subjective responses starting at the 25 µg dose. A ceiling effect was observed for good drug effects at the 100 µg dose. Hence we conclude that Ketanserin almost completely prevented the response to the high (200 µg) dose of LSD, thus confirming the critical role of 5-HT2A receptors in mediating psychedelic effects of LSD.
Ref: https://www.nature.com/articles/s41386-020-00883-6
