European journal of pharmacology
July 15, 2025
Isis Koutrouli, Kristýna Mazochová, Rachel R Horsley
4 citations
A selective review of preclinical rodent studies suggests that (2R,6R)-hydroxynorketamine ((2R,6R)-HNK), a metabolite of ketamine, reduces behavioral despair, anhedonia, anxiety, and social avoidance in both stressed and non-stressed animals. Antidepressant effects appear rapidly (within 30 minutes) and last up to 21 days at doses between 5 and 125 mg/kg. However, some studies failed to find significant effects at doses below 40 mg/kg, particularly in models with pre-induced depression. No major adverse effects were reported, though side-effect data were limited. The authors conclude that (2R,6R)-HNK shows promise as a next-generation antidepressant but requires further research on long-term safety and mechanisms.
The international journal of neuropsychopharmacology
August 1, 2025
Klára Šíchová, Barbara Mallarino, Lucie Janečková et al.
1 citation
Hexahydrocannabinol (HHC), a new psychoactive substance used as a legal alternative to ∆9-tetrahydrocannabinol, crosses the blood-brain barrier, exhibits mild toxicity, and induces behavioral effects similar to tetrahydrocannabinol in male Wistar rats. A 1:1 mixture of (9R)-HHC and (9S)-HHC was given at doses of 1, 5, and 10 mg/kg. Two hours after the highest dose, peak concentrations appeared in blood and brain tissue. The OECD 423 test classified HHC as Category 4, with an estimated lethal dose of 1000 mg/kg. Compared to controls, 10 mg/kg HHC reduced movement, increased anxiety, and impaired sensory processing, highlighting dose-dependent anxiogenic properties and impact on information processing.
Progress in neuro-psychopharmacology & biological psychiatry
July 5, 2025
Hynek Danda, Kristýna Mazochová, Klára Šíchová et al.
1 citation
Baeocystin, a compound found in psychoactive mushrooms, has minimal to no behavioral effects in rats, likely because it poorly crosses the blood-brain barrier. After subcutaneous doses of 1.25 or 5 mg/kg, baeocystin and its metabolite norpsilocin showed very limited brain penetration. Consistent with this, the compound had no significant effects on locomotor activity, exploratory behavior, anxiety-like responses, or sensorimotor gating in Wistar rats. The findings suggest baeocystin's negligible neurobiological and psychedelic activity is due to its poor permeability across the blood-brain barrier.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
June 1, 2025
Natalie Paškanová, Magdaléna Vágnerová, Bronislav Jurásek et al.
1 citation
Methoxphenidine (MXP), a dissociative anaesthetic derivative, is increasingly abused, but forensic and clinical data on its metabolism and enantiomers are limited. Researchers developed and validated achiral LC-MS/MS and chiral SFC-MS methods to quantify MXP and its primary metabolite, O-desmethyl-methoxphenidine (dmMXP), in rat serum and brain after a single subcutaneous dose of racemic MXP. Serum MXP peaked at 1600 ng/mL at 0.5 hours and decreased to 5.87 ng/mL at 24 hours; brain MXP peaked at 13200 ng/g at 0.5 hours and fell to 36.1 ng/g at 24 hours. (S)-MXP concentrations in brain appeared higher than (R)-enantiomer concentrations. The methods enable pharmacokinetic studies and provide tools for forensic and clinical toxicology.
Pharmacology, biochemistry, and behavior
June 30, 2026
Lucie Ladislavová, Viera Kútná, Kristýna Mazochová et al.
Chronic microdosing of psilocin (0.05 or 0.075 mg/kg) in adult male Wistar rats over five weeks did not alter locomotor activity, depressive-like behavior, sociability, or novelty seeking, and did not increase cell proliferation in the dentate gyrus of the hippocampus. A small anxiogenic effect was detected in the Elevated Plus Maze. The findings suggest that, under this dosing schedule, psilocin microdosing produces limited behavioral effects and does not enhance hippocampal progenitor proliferation.