In contrast to previous studies, we used pharmaceutically well-defined doses of LSD. Therefore, the present study evaluated acute subjective and autonomic effects of LSD across a range of relevant doses in healthy subjects. No recent data are available on the acute effects of different well-defined psychoactive doses of LSD in humans and within the same study.
However, all recent placebo-controlled high-dose studies of LSD used only single doses. Renewed interest has been seen in using LSD in psychiatric research and to assist psychotherapy. LSD induces a range of complex alterations of the mind that have been shown to depend on serotonin 5-hydroxytryptamine-2A (5-HT 2A) receptor stimulation. Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic with a broad history of early psychiatric research and recreational use. The full psychedelic effects of LSD are primarily mediated by serotonin 5-HT 2A receptor activation. These results may assist with dose finding for future LSD research. 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. Ketanserin effectively prevented the response to 200 µg LSD. LSD moderately increased blood pressure and heart rate. The average duration of subjective effects increased from 6.7 to 11 h with increasing doses of 25–200 µg.
The 200 µg dose of LSD induced greater ego dissolution than the 100 µg dose and induced significant anxiety.
A ceiling effect was observed for good drug effects at 100 µg. LSD showed dose-proportional pharmacokinetics and first-order elimination and dose-dependently induced subjective responses starting at the 25 µg dose. The pharmacokinetic-subjective response relationship was evaluated. Outcome measures included self-rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain-derived neurotrophic factor levels, and pharmacokinetics up to 24 h. Test days were separated by at least 10 days. We used a double-blind, randomized, placebo-controlled, crossover design in 16 healthy subjects (eight women, eight men) who underwent six 25 h sessions and received placebo, LSD (25, 50, 100, and 200 µg), and 200 µg LSD 1 h after administration of the serotonin 5-hydroxytryptamine-2A (5-HT 2A) receptor antagonist ketanserin (40 mg). However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well-defined doses of LSD. Growing interest has been seen in using lysergic acid diethylamide (LSD) in psychiatric research and therapy.
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