Psilocin, the active metabolite of the psychedelic compound psilocybin, is being studied for treating anxiety, depression, and PTSD. Evaluating its pharmacokinetics is essential for drug development. During reversed-phase liquid chromatography analysis of mouse plasma, a previously unreported interference was encountered. The interference was identified as tryptophan using exact mass measurement and MS/MS analysis. A fast and reliable hydrophilic interaction liquid chromatography–tandem mass spectrometry (HILIC-MS/MS) method was developed and validated that separates psilocin from tryptophan, achieving a lower limit of quantification of 0.5 ng/ml. The method was successfully applied to a pharmacokinetic study in C57BL/6 mice, determining psilocin concentrations in all analyzed plasma samples.
LSD, psilocybin, and psilocin are being evaluated as potential treatments for depression, anxiety, substance use disorder, and other psychiatric conditions. Pre-clinical research in rodents is key to their drug development. This review summarizes evidence on these compounds in rodent models of the psychedelic experience, behavior, substance use, alcohol consumption, drug discrimination, anxiety, depression-like behavior, stress response, and pharmacokinetics. The authors identify three knowledge gaps for future research: sex differences, oral dosing instead of injection, and chronic dosing regimens. A thorough understanding of the in vivo pharmacology of these compounds may aid their clinical use and serve as controls for developing novel psychedelic therapeutics.
Prenatal exposure to Δ9-tetrahydrocannabinol (THC), the main intoxicating compound in cannabis, alters brain chemistry in offspring. Using X-ray fluorescence imaging and Fourier transform infrared spectromicroscopy on rat brains, the study found that THC-exposed offspring had decreased copper concentrations in the corpus callosum and changes in lipid structure, including increased methylene, lipid esters, phosphate, protein, and unsaturation levels, particularly in the hippocampus. Biochemical changes were modest, with increased structural lipid changes in the corpus callosum and increased protein in the lateral ventricle. These findings demonstrate that gestational THC induces subtle but measurable biomolecular alterations in the developing brain.