Neurobiology of psilocybin: a comprehensive overview and comparative analysis of experimental models

Psilocybin, from Psilocybe mushrooms, shows promise for treating neurodegenerative and psychiatric disorders like major depressive disorder by promoting neuroprotection, neurogenesis, and neuroplasticity. It may help combat mild neurodegeneration by increasing synaptic density and supporting neuronal growth, with low addiction risk and few adverse effects. Animal models, including Drosophila and fish, have provided insights into its mechanisms, aiding high-throughput screening of neural development, behavior, and genetic pathways. While mammalian models are needed for pharmacokinetics and complex nervous system interactions, small non-mammalian models help identify early targets. This complementary approach suggests psilocybin could potentially halt or reverse neurodegenerative processes.

Study at a glance

Abstract

Psilocybin, a compound found in Psilocybe mushrooms, is emerging as a promising treatment for neurodegenerative and psychiatric disorders, including major depressive disorder. Its potential therapeutic effects stem from promoting neuroprotection, neurogenesis, and neuroplasticity, key factors in brain health. Psilocybin could help combat mild neurodegeneration by increasing synaptic density and supporting neuronal growth. With low risk for addiction and adverse effects, it presents a safe option for long-term use, setting it apart from traditional treatments. Despite their relatively simpler neuronal networks, studies using animal models, such as Drosophila and fish, have provided essential insights on the efficacy and mechanism of action of psilocybin. These models provide foundational information that guides more focused investigations, facilitating high-throughput screening, enabling researchers to quickly explore the compound’s effects on neural development, behavior, and underlying genetic pathways. While mammalian models are indispensable for comprehensive studies on psilocybin’s pharmacokinetics and its nuanced interactions within the complex nervous systems, small non-mammalian models remain valuable for identifying promising targets and mechanisms at early research stages. Together, these animal systems offer a complementary approach to drive rapid hypothesis generation to refine our understanding of psilocybin as a candidate for not only halting but potentially reversing neurodegenerative processes. This integrative strategy highlights the transformative potential of psilocybin in addressing neurodegenerative disorders, leveraging both small and mammalian models to achieve translational research success.