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.
Journal of psychopharmacology (Oxford, England)
May 28, 2025
Yana Vella, Kateřina Syrová, Aneta Petrušková et al.
1 citation
Psilocin, the active compound in magic mushrooms, promotes the formation of new synapses in rat brain cells, an effect comparable to ketamine and lithium. In laboratory experiments on rat cortical cultures, psilocin increased the number of synaptic puncta and boosted expression of the immediate early gene Arc after acute treatment. Lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT) did not produce significant synaptogenic effects. Fluoxetine, a common antidepressant, had no effect on synapse formation but upregulated other immediate early genes. These findings add evidence that psilocin may be a promising therapeutic agent for psychiatric conditions.
bioRxiv Preprint Server
August 7, 2024
Yana Vella, Kateřina Syrová, Aneta Petrušková et al.
1 citation
preprint
Psychedelics can produce rapid and lasting antidepressant effects, likely through neuroplasticity, though the precise molecular mechanisms are not yet understood.
Addiction Biology
March 1, 2026
Isis Koutrouli, Vojtěch Brejtr, Marek Schwendt et al.
Psilocybin and ibogaine, given in a dose-escalation protocol, facilitated extinction learning in male rats that had self-administered cocaine. Psilocybin reduced active lever pressing one day after the second dose, with a nonsignificant reduction after the first dose; ibogaine significantly reduced pressing even after the first administration. Neither drug significantly altered cue-induced reinstatement of drug-seeking, though psilocybin showed a trend toward attenuation. The treatments had no side effects on general locomotor activity or anxiety-like behavior in the open field test. These results suggest psilocybin and ibogaine may support extinction learning and possibly protect against relapse, warranting further research into their antiaddictive potential.