Psychological medicine
March 1, 2023
Isabel Wießner, Marcelo Falchi, Fernanda Palhano-Fontes et al.
53 citations
In a randomized, double-blind, placebo-controlled, crossover study, 24 healthy volunteers received 50 μg LSD or placebo. LSD produced psychedelic experiences, including altered consciousness, mystical experiences, ego-dissolution, and mildly challenging experiences, and increased aberrant salience and suggestibility, but not mindfulness. LSD-induced aberrant salience correlated strongly with complex imagery, mystical experiences, and ego-dissolution. Suggestibility changes from LSD did not correlate with other effects. The results suggest the LSD state resembles psychosis and may offer a therapeutic tool, with mystical experiences linking the psychosis model and therapeutic potential. Meaning attribution appears important for the LSD psychosis model, and psychedelic-assisted therapy might benefit from suggestions that foster mystical experiences.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
May 1, 2022
Isabel Wießner, Rodolfo Olivieri, Marcelo Falchi et al.
42 citations
A low dose of LSD (50 μg) produces both beneficial and detrimental cognitive effects 24 hours after administration. Compared to placebo, LSD sub-acutely improved visuospatial memory and phonological verbal fluency but impaired cognitive flexibility, as measured by fewer categories achieved and more perseveration on the Wisconsin Card Sorting Test. The findings suggest that LSD-assisted therapy might be explored for conditions involving memory and language decline, such as brain injury, stroke, or dementia, while also indicating a mixed 'afterglow and hangover' profile.
Experimental Neurology
June 1, 2022
I. Ornelas, F. A. Cini, Isabel Wießner et al.
37 citations
LSD treatment improved performance in a novel object recognition task in rats and a visuo-spatial memory task in humans. A proteomic analysis of human brain organoids showed that LSD affected metabolic pathways associated with neural plasticity, including mTOR. Simulations using a neural network model of a cortico-hippocampal circuit, with baseline plasticity strength as a proxy for age and increased plasticity related to LSD dose, fit the experimental data well. The results suggest that LSD has nootropic effects.
Psychopharmacology
June 1, 2022
Isabel Wießner, Marcelo Falchi, Fernanda Palhano-Fontes et al.
22 citations
LSD alters the stream of thought in multiple ways, increasing chaos, meaning, and abstractness at different times after ingestion. In a randomized, double-blind, placebo-controlled crossover study with 24 healthy participants, 50 μg LSD compared to placebo induced facets of mind-wandering labeled 'chaos' (discontinuity of mind, decreased sleepiness and planning), 'meaning' (deep thoughts), and 'sensation' (thoughts about odors and sounds). LSD also increased free association for abstract words, reflecting an 'abstract flow.' Chaos was strongest from 2 to 6 hours after dosing, meaning from 2 to 4 hours, sensation at 2 hours, and abstract flow at 4 hours. The findings suggest a late therapeutic window around 4 hours for psycholytic therapy.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
March 1, 2023
Isabel Wießner, Marcelo Falchi, Dimitri Daldegan-Bueno et al.
6 citations
Low to moderate doses of LSD alter language structure, semantics, and vocabulary over time. In a double-blind, placebo-controlled crossover study, 24 healthy volunteers (age 35±11, 33% women) received 50 μg LSD or placebo. LSD reduced verbosity, lexicon, and connectivity in speech networks from 1.5 to 4 hours, decreased semantic distances between words from 2 to 24 hours, and shifted vocabulary related to grammar, persons, time, space, and biological processes from 1.5 to 24 hours. Simpler, disconnected structure and increased semantic similarity may reflect cognitive impairments, while vocabulary changes may indicate subjective perceptual shifts. Automated language analysis could offer unconstrained insights into psychedelic cognition.