Daily Administration of Psilocin Mucate (L-130) Produces a Favorable Safety Profile and Anxiolytic Effects in Rodents Exposed to Chronic Unpredictable Mild Stress.

Abstract

Anxiety disorders are chronic health conditions affecting the quality of life of millions of people. Psilocin, the active moiety of psilocybin, provides an anxiolytic effect; however, when orally administered as psilocybin, it only offers a moderate level of bioavailability and less predictable pharmacokinetics, potentially making effects after absorption variable and increasing the risk of adverse hallucinations, depending on the dose. As such, we investigated a recently developed stable salt of psilocin, psilocin mucate (L-130), which delivers increased bioavailability and, thus, more precise control of therapeutic levels. We examined factors related to L-130's safety, as well as its effectiveness in addressing anxiety at a commonly used macro dose level, along with dosing schedules similar to those noted in the literature. Clinical assessments and blood analyses suggest psilocin mucate is safe and has no toxicological effects. Compared to vehicle controls, daily dosing of L-130 led to significant reductions in cortisol levels and improved performances on several anxiety-related behavioral tasks: the Elevated Plus Maze, the Open Field Test, and the Novel Object Recognition Task. However, weekly dosing did not generally produce significant results. Overall, daily dosing of L-130 was able to produce anxiolytic behaviors, but larger studies are needed to determine optimal doses and dosing schedules.

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