PloS one
January 1, 2024
Kristian Elersič, Anamarija Banjac, Marko Živin et al.
6 citations
Ketamine's antidepressant potential is limited by side effects such as motor impairment. In rats, repeated low doses of ketamine enantiomers produced distinct behavioral changes. S-ketamine at 15 mg/kg caused initial locomotor stimulation and ataxia, while repeated administration led to locomotor sensitization and tolerance to ataxia. R-ketamine at 15 mg/kg also stimulated locomotion and caused sensitization but did not induce ataxia or reduce natural behaviors like grooming and rearing. Higher doses of racemic ketamine (30 mg/kg) produced both stimulation and ataxia. Overall, S-ketamine had stronger behavioral effects than R-ketamine, suggesting R-ketamine may have a more favorable side-effect profile.
Journal of psychiatric research
April 1, 2025
Kristian Elersič, Anamarija Banjac, Marko Živin et al.
3 citations
Ketamine, a fast-acting antidepressant, is a racemic mixture of R- and S-ketamine. In a preclinical study using Wistar-Kyoto rats (a depression model) and Wistar rats (controls), researchers compared behavioral effects of R- and S-ketamine at 10 mg/kg in a clinically relevant treatment protocol. S-ketamine produced stronger acute psychomotor effects (locomotor stimulation, ataxia, stereotypy) than R-ketamine, and Wistar-Kyoto rats were more sensitive to these effects. After repeated treatment, sensitization to locomotor stimulation and tolerance to ataxic effects of S-ketamine developed. No persistent changes in working memory, anxiety, or behavioral despair were found. Results suggest depressed individuals may be more prone to negative side effects, but tolerance may develop with repeated treatment.
March 20, 2024
Aleš Oblak, Liam Korošec Hudnik, Anja Levačić et al.
1 citation
preprint
Psilocybin microdosing loosens mental structures, making thoughts less intense and thinking more flexible but less stable, while increasing the salience of external stimuli—sometimes making mundane activities more interesting, sometimes causing sensory overload. The experience is appraised more positively in highly structured environments. Momentary ecological assessments and retrospective interviews gave completely opposite accounts of the experience, highlighting profound methodological challenges in microdosing research. The findings relate to stable versus flexible cognition and the concept of salience, underscoring the need for systematic mixed-methods studies to better characterize the lived experience of psilocybin microdosing.