Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants

被引:47
作者
Becker, Anna M. [1 ,2 ,3 ,4 ]
Klaiber, Aaron [1 ,2 ,3 ]
Holze, Friederike [1 ,2 ,3 ,4 ]
Istampoulouoglou, Ioanna [1 ,2 ,3 ,4 ]
Duthaler, Urs [1 ,2 ,3 ,4 ]
Varghese, Nimmy [5 ,6 ]
Eckert, Anne [5 ,6 ]
Liechti, Matthias E. [1 ,2 ,3 ,4 ,7 ]
机构
[1] Univ Hosp Basel, Clin Pharmacol & Toxicol, Dept Biomed, Basel, Switzerland
[2] Univ Hosp Basel, Dept Clin Res, Basel, Switzerland
[3] Univ Basel, Basel, Switzerland
[4] Univ Basel, Dept Pharmaceut Sci, Basel, Switzerland
[5] Univ Basel, Psychiat Univ Hosp, Basel, Switzerland
[6] Univ Basel, Transfac Res Platform Mol & Cognit Neurosci, Basel, Switzerland
[7] Univ Hosp Basel, Clin Pharmacol, Schanzenstr 55, CH-4056 Basel, Switzerland
关键词
LSD; ketanserin; interaction; subjective effects; pharmacokinetics; LYSERGIC-ACID DIETHYLAMIDE; MYSTICAL-TYPE EXPERIENCES; LIFE-THREATENING CANCER; PSILOCYBIN TREATMENT; ANXIETY; PHARMACOKINETICS; DEPRESSION; DISCOVERY;
D O I
10.1093/ijnp/pyac075
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background Lysergic acid diethylamide (LSD) is currently being investigated in psychedelic-assisted therapy. LSD has a long duration of acute action of 8-11 hours. It produces its acute psychedelic effects via stimulation of the serotonin 5-hydroxytryptamine-2A (HT2A) receptor. Administration of the 5-HT2A antagonist ketanserin before LSD almost fully blocks the acute subjective response to LSD. However, unclear is whether ketanserin can also reverse the effects of LSD when administered after LSD. Methods We used a double-blind, randomized, placebo-controlled, crossover design in 24 healthy participants who underwent two 14-hour sessions and received ketanserin (40 mg p.o.) or placebo 1 hour after LSD (100 mu g p.o.). Outcome measures included subjective effects, autonomic effects, acute adverse effects, plasma brain-derived neurotrophic factor levels, and pharmacokinetics up to 12 hours. Results Ketanserin reversed the acute response to LSD, thereby significantly reducing the duration of subjective effects from 8.5 hours with placebo to 3.5 hours. Ketanserin also reversed LSD-induced alterations of mind, including visual and acoustic alterations and ego dissolution. Ketanserin reduced adverse cardiovascular effects and mydriasis that were associated with LSD but had no effects on elevations of brain-derived neurotrophic factor levels. Ketanserin did not alter the pharmacokinetics of LSD. Conclusions These findings are consistent with an interaction between ketanserin and LSD and the view that LSD produces its psychedelic effects only when occupying 5-HT2A receptors. Ketanserin can effectively be used as a planned or rescue option to shorten and attenuate the LSD experience in humans in research and LSD-assisted therapy. Trial registry ClinicalTrials.gov (NCT04558294)
引用
收藏
页码:97 / 106
页数:10
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