Characterization of Psilocin and Psilocybin Pharmacodynamics in Mouse Models for the Development of Novel Anti-Depressants

There is growing interest in Canada and around the world with respect to the potential benefits of psychedelic compounds for the treatment of psychiatric conditions. This interest has led to a surge in biomedical research into the effects of psychedelic compounds, their pharmacology, potential clinical uses, as well as their harms. Consequently, our current understanding of psychedelic compounds – the most prominent being lysergic acid diethylamide (LSD), psilocybin, and psilocin – is presently drawn from foundational studies from before 1990 and the more recent body of literature that is part of this surge. The purpose of this research was to further our understanding of the pharmacological activity of such drugs as demand for therapeutics, that may provide better benefits and less detrimental side effects than those already on the market (e.g., serotonin selective reuptake inhibitors [SSRIs]), increases. Through in vivo experiments measuring head twitch response (HTR), catalepsy, internal body temperature, analgesia using the tail flick response assay, and locomotion in the open field we assessed the pharmacological activity of LSD (positive control), psilocybin, and psilocin. Anxiety and depression- like behaviors were measured in the elevated plus maze (EPM) and forced swim test (FST), respectively. We observed a biphasic response in the HTR for all 3 drugs, with psilocin and psilocybin displaying their peak activity at 1 mg/kg and 3mg/kg, respectively. Psilocin - and to a lesser extent psilocybin – produced a dose-dependent hypothermia in mice. We also observed dose-dependent hypolocomotion when measuring both distance traveled and velocity, as well as a dose-dependent decrease in time spent in the centre quadrant of the open field (OFT). A biphasic anti-nociceptive effect was observed for psilocin, with peak anti-nociceptive effects seen at 1 mg/kg, which was greater in magnitude than psilocybin. Treatment with psilocin or psilocybin did not produce catalepsy. Oral gavage of mice with 3 mg/kg psilocin did not change behavior in the FST or EPM. Overall, psilocin and psilocybin produced in vivo responses consistent with acute serotonergic activity but did not produce the anxiolytic or anti-depressant effects anticipated. Future research needs to explore the utility of these substances as therapeutics in more detail in pre-clinical studies before their inclusion as acceptable medicines.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.