Characterizing Brain Targets of a Novel Antidepressant: Using Psychedelic Worms to Study Mood Disorder Drugs

Alyssa Garbarino, Leighton Ledesma, and Dr. Gareth Harris


Mood disorders, such as depression affect over 40 million people in the US, despite the use of an array of therapeutics for mood disorders. Current understanding of the mechanisms underlying these processes and specific targets of each therapeutic is rudimentary; resulting in variable success of the existing treatments aimed to relieve symptoms of mood disorders. More recently, there has been a deeper focus on the use of known recreationally used compounds as potential therapies for neurological disorders, including Magic Mushroom’s main hallucinogen Psilocybin. We use the worm, Caenorhabditis elegans, to investigate the behavioral effects of ‘Psilocybin and its known neurologically active metabolite, Psilocin. We aim to further identify the potential molecular mechanisms to further our understanding of the brain targets of Psilocybin/Psilocin, using worms to achieve these goals. Interestingly, we have found that Psilocybin/Psilocin exposure influences multiple worm behavior’s, including movement and egg laying. Many of the genes in the worm share significant conservation with humans, which provides an avenue to identify effects of human relevant compounds, like Psilocybin/Psilocin. We have begun to characterize the role of neuronal signals in Psilocin-dependent stimulation of egg laying and inhibition of movement. We have identified multiple neurotransmitter systems, synaptic transmission/neurosecretion genes, and G-protein signaling that are responsible for Psilocin-dependent effects. We hope to provide a platform for elucidating the molecular mechanisms and neural networks that are influenced through exposure to Psilocybin/Psilocin, especially in light of Psilocybin/Psilocin becoming increasingly appreciated as a potential therapy for treatment of depression, PTSD, and addiction.

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