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However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well-defined doses of LSD. We used a double-blind, randomized, placebo-controlled, crossover design in 16 healthy subjects (eight women, eight men) who underwent six 25\u2009h sessions and received placebo, LSD (25, 50, 100, and 200\u2009\u00b5g), and 200\u2009\u00b5g LSD 1\u2009h after administration of the serotonin 5-hydroxytryptamine-2A (5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    ) receptor antagonist ketanserin (40\u2009mg). Test days were separated by at least 10 days. 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\u2009h. The pharmacokinetic-subjective response relationship was evaluated. LSD showed dose-proportional pharmacokinetics and first-order elimination and dose-dependently induced subjective responses starting at the 25\u2009\u00b5g dose. A ceiling effect was observed for good drug effects at 100\u2009\u00b5g. The 200\u2009\u00b5g dose of LSD induced greater ego dissolution than the 100\u2009\u00b5g dose and induced significant anxiety. The average duration of subjective effects increased from 6.7 to 11\u2009h with increasing doses of 25\u2013200\u2009\u00b5g. LSD moderately increased blood pressure and heart rate. Ketanserin effectively prevented the response to 200\u2009\u00b5g LSD. The LSD dose\u2013response curve showed a ceiling effect for subjective good effects, and ego dissolution and anxiety increased further at a dose above 100\u2009\u00b5g. These results may assist with dose finding for future LSD research. The full psychedelic effects of LSD are primarily mediated by serotonin 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    receptor activation.\n                  <\/jats:p>","DOI":"10.1038\/s41386-020-00883-6","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T16:02:44Z","timestamp":1602777764000},"page":"537-544","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":226,"title":["Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects"],"prefix":"10.1038","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3143-1519","authenticated-orcid":false,"given":"Friederike","family":"Holze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5954-4446","authenticated-orcid":false,"given":"Patrick","family":"Vizeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Dolder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Stocker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs","family":"Duthaler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimmy","family":"Varghese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-3669","authenticated-orcid":false,"given":"Anne","family":"Eckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Borgwardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1765-9659","authenticated-orcid":false,"given":"Matthias E.","family":"Liechti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"883_CR1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1755-5949.2008.00059.x","volume":"14","author":"T Passie","year":"2008","unstructured":"Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A. 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