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.