Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants
The International Journal of Neuropsychopharmacology November 4, 2022 Aaron Klaiber, Friederike Holze, Ioanna Istampoulouoglou et al. 100 citations
Lysergic acid diethylamide (LSD) produces its acute psychedelic effects by stimulating the serotonin 5-HT2A receptor. In a double-blind, randomized, placebo-controlled, crossover study with 24 healthy participants, the 5-HT2A antagonist ketanserin (40 mg orally) was given one hour after LSD (100 µg orally). Ketanserin reversed the acute response to LSD, reducing the duration of subjective effects from 8.5 hours with placebo to 3.5 hours. It also reversed LSD-induced alterations of mind, including visual and acoustic alterations and ego dissolution, and reduced adverse cardiovascular effects and mydriasis. Ketanserin did not alter LSD's pharmacokinetics or its elevation of brain-derived neurotrophic factor levels. The findings indicate that LSD produces its psychedelic effects only when occupying 5-HT2A receptors, and ketanserin can shorten and attenuate the LSD experience for research and therapy.