Journal of Psychopharmacology
November 4, 2020
Oskar Hougaard Jefsen, Betina Elfving, Gregers Wegener et al.
123 citations
Psilocybin, the psychoactive compound in magic mushrooms, rapidly alters the activity of genes linked to neuroplasticity, with stronger effects in the prefrontal cortex than in the hippocampus. In rats given a single dose of 0.5–20 mg/kg, psilocybin increased expression of ten genes in the prefrontal cortex (including c-Fos, Fosb, and Nr4a1) and decreased one. In the hippocampus, it increased four genes (e.g., Sgk1, Dusp1) and decreased four others (e.g., Arc, Egr2). Protein levels for three key genes only partly matched the gene activity changes, indicating that measuring gene expression alone may not fully capture the drug's effects. These findings support psilocybin's potential to rapidly promote brain plasticity.
Acta Neuropsychiatrica
May 20, 2019
Oskar Hougaard Jefsen, Kristoffer Højgaard, Sofie Laage Christiansen et al.
66 citations
Psilocybin, a serotonin receptor agonist being studied for treatment-resistant depression, showed no antidepressant-like effect in a rat model of depression. In Flinders Sensitive Line rats, which model depression, neither psilocybin nor its active form psilocin reduced immobility time in the forced swim test, a standard measure of antidepressant activity. The drugs also did not alter locomotor activity in an open field test, ruling out stimulant effects. The rats bred to be depression-prone did show more immobility than their control counterparts, confirming the model's validity. The findings suggest that different animal models and behavioral tests may better translate the positive effects of psilocybin observed in humans.
Pharmacological research
January 1, 2025
Nicole R Silva, Shokouh Arjmand, Luana B Domingos et al.
6 citations
In a rat model of depression (Flinders Sensitive Line), depressive behavior was negatively correlated with levels of the endocannabinoid 2-AG. A single dose of S-ketamine restored 2-AG levels and increased endocannabinoid signaling in the prefrontal cortex. Although S-ketamine decreased gene expression of the CB1 receptor and the enzyme FAAH, protein levels did not change significantly. S-ketamine increased CB1 receptor binding, and computer modeling suggested it may bind to CB1, CB2, GPR55, and FAAH. However, blocking CB1 receptors with rimonabant did not prevent S-ketamine's behavioral effects, indicating a complex interaction with the endocannabinoid system that requires further study.
European psychiatry : the journal of the Association of European Psychiatrists
February 5, 2025
Shokouh Arjmand, Mats B Lindström, Carl M Sellgren et al.
1 citation
The dissociative effects of ketamine and psychedelics may be linked to their rapid antidepressant properties, but it is unclear whether these effects are necessary for therapeutic action. Because patients can often tell whether they received an active drug or placebo based on the dissociative experience, clinical trial results may be biased. The authors propose a novel approach: administering these drugs to patients during sleep to separate the subjective dissociative experience from the drug's biological effects, potentially allowing for better-controlled studies.
Synapse (New York, N.Y.)
July 1, 2024
Simone Larsen Bærentzen, Jakob Borup Thomsen, Majken Borup Thomsen et al.
1 citation
Acute administration of S-ketamine, a fast-acting antidepressant, did not alter dopamine transporter (DAT) availability in the striatum of healthy female rats, as measured by [18F]FE-PE2I PET imaging and [3H]GBR-12935 autoradiography. This negative result suggests that changes in DAT binding are not involved in S-ketamine's rapid antidepressant mechanism, though further research is needed.