In Canada, over 1 million people have been diagnosed with bipolar disorder (BD) in their lifetime. BD is characterized by recurrent episodes of depression and (hypo)mania. Many people do not improve when they receive a recommended treatment, leading to treatment resistance. Psilocybin has been identified as a potential option to alleviate the symptoms of depression through psilocybin-assisted therapy (PAT). One way that this drug might act in the brain is through what is known as neuroplasticity – where your brain creates new connections or strengthens existing ones. Synapses are connections between neurons, which are cells in the brain. Psilocybin may improve depression symptoms by increasing the density of synapses.
In this study, we will recruit people who are participating in a randomized controlled trial examining PAT in treatment resistant depression associated with bipolar II disorder. Participants will complete a positron emission tomography/magnetic resonance imaging (PET/MRI) scan – a type of brain scan which can measure the density of synapses and neurons in the brain. This scan uses a radioactive tracer called [18F]SYNVEST-1 to measure density of synapses. Scans will happen before and 4 weeks after receiving a single dose of psilocybin at either 25mg or 1mg. We will compare changes in the brain before and after the psilocybin dose, as well as compare groups once we know which dose they received, at the end of the main trial. The primary aim of this study is to see if it is feasible to do this imaging study with a PAT trial. Secondary aims are to see whether there are changes in synaptic density in specific brain areas that are involved in BD and if changes in synaptic density are associated with cognitive or mood changes. Results from this study will provide insights on how psilocybin acts as an antidepressant.
