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.
Comprehensive psychoneuroendocrinology
February 1, 2023
Daniel Rødbro Burmester, Martin Korsbak Madsen, Attila Szabo et al.
24 citations
A single dose of psilocybin did not significantly change peripheral biomarkers of inflammation—high-sensitivity C-reactive protein (hsCRP), tumor-necrosis-factor (TNF), and soluble urokinase plasminogen activator receptor (suPAR)—in 16 healthy individuals one day after administration. All effect sizes were small (Cohen's d ≤ 0.31) and p-values were ≥ 0.23. These findings do not support that a single dose of psilocybin reduces inflammation in healthy people, though future studies should examine additional markers and clinical populations where effects may be more detectable.
ACS Pharmacology & Translational Science
May 29, 2025
Meghan Hibicke, Erik Kaadt, Emil Märcher-Rørsted et al.
3 citations
A new compound, LPH-5, acts as a potent partial agonist at the 5-HT2A receptor with high selectivity over related 5-HT2B and 5-HT2C receptors. In rats, LPH-5 induced head-twitch responses and produced both acute and persistent antidepressant-like effects. These findings suggest that selective activation of the 5-HT2A receptor alone can produce antidepressant effects, indicating that this receptor is a key component in the therapeutic action of classical psychedelics like psilocybin and LSD.
bioRxiv Preprint Server
April 19, 2024
Anders A. Jensen, Claudia R. Cecchi, Meghan Hibicke et al.
preprint
A new compound called LPH-5 selectively activates the 5-HT2A receptor, unlike classical psychedelics which also affect related receptors. In rats, LPH-5 produced head-twitch responses (a behavioral marker of 5-HT2A activation) at doses of 0.5-1.0 mg/kg and showed antidepressant-like effects in three different rat models: Flinders Sensitive Line rats, adrenocorticotropic hormone-treated Sprague Dawley rats, and a Wistar Kyoto rat model designed to capture long-term antidepressant effects. The findings suggest that selective 5-HT2A receptor activation is sufficient for antidepressant potential, and that LPH-5 or similar selective compounds could represent a new generation of antidepressant drugs derived from psychedelics.
Research Square
January 12, 2024
Erik Kaadt, Rolf Søkilde, Hanne D. Hansen et al.
A single dose of psilocybin alters the expression of specific microRNAs (miRNAs) in the prefrontal cortex and hippocampus of pigs, brain regions central to depression. One day after administration, 12 miRNAs were dysregulated in the prefrontal cortex and 2 in the hippocampus; after one week, only 4 dysregulated miRNAs remained in the hippocampus. Nine of the 18 identified miRNAs have been previously linked to depression. Two miRNAs, miR-212-3p and miR-107, showed robust acute regulation in the prefrontal cortex and are known to exert anti-inflammatory effects, mirroring previously reported effects of psilocybin. These results suggest psilocybin may exert its molecular effects through miRNA regulation.