Usage of Psilocybin to Treat Huntington's Disease: A Research Protocol

Introduction: Huntington’s Disease (HD) is a progressive, neurodegenerative disease that causes significant amounts of neuron death in the brain. It is a genetic disorder, resulting from the over-repetition of the CAG sequence in the gene that codes for the huntingtin protein. Currently, there are no viable cures or treatments to slow or stop the progression of this disorder, making it a target candidate for treatment research. However, given the difficulty and complexity of in treating the genetic cause of HD in adults, a more viable approach may involve treating the resulting neurodegeneration with neuroprotective compounds, such as psilocybin. As such, our study proposes the usage of psilocybin to treat HD due to its neuroprotective, neurotrophic, and neuroplastic effects, resulting in a decreased rate of neuron loss and increased synaptic density. Methods: We propose an in-vivo experiment using several groups of zQ175 knock-in (KI) mice, which will mimic HD in the mice. Following 8 weeks, the mice’s brains will be extracted at different time intervals to analyze the progression of neuronal death using histology and immunohistochemistry, which should inform us about the progression of HD in the different groups of mice. Moreover, throughout this experiment, the motor control of the mice will be observed using the rotarod test, the raised beam test, and the footprint test. Data from these tests will act as behavioral markers for HD, providing an alternate source of information on the progression of HD in the mice. Expected Results: KI mice are expected to have lower rates of neuronal death, higher amounts of synaptic density, and higher scores on average across the three motor behavior tests, compared to the non-treated KI mice. Discussion: These results could provide insight into potential treatments for slowing the progression of HD. If successful, possible next steps could be to determine the efficacy of psilocybin in clinical trials for HD. Conclusion: This study is expected to provide information on the usage of psilocybin as a treatment for HD. If the expected results are obtained, psilocybin may help improve the quality of life for those afflicted with HD.