SPEAKERS

There is growing interest in the therapeutic utility of psilocybin for increasingly common and difficult to treat disorders. Thus an important question is how psilocybin acts in the brain. Accumulating evidence suggests that psilocybin stimulates 5-HT2A receptors located on neocortical pyramidal cells, which is the suggested primary mechanisms of action for the hallucinogenic effect. However, it has also been recognized that psilocybin elevates levels of cortical glutamate, which has been implicated in the acute actions of the substance on brain function and behavior. To our knowledge, no study has yet investigated the acute effect of a psychedelic on brain glutamate levels in humans. Therefore, the aim of the present study was to assess the acute influence of psilocybin on glutamate levels in the medial prefrontal cortex (mPFC) and hippocampus, as well as the relationship between glutamate levels, and brain and behavioral outcomes previously found to be affected by psychedelics, including disrupted within-network functional connectivity (FC) and well-known subjective effects (5D-ASC). Sixty healthy participants were allocated to a treatment condition (.17 mg/kg psilocybin or placebo) and underwent 1H-MRS and resting state fMRI 60 minutes posttreatment. Psilocybin increased glutamate levels in the mPFC, and decreased glutamate levels in the hippocampus. FC alterations were consistent with previous psychedelic imaging results. Alterations in metabolite levels were correlated with changes in subjective state. Metabolite and FC correlation analysis is ongoing and further results will be presented. Preliminary results suggest that glutamate may play an important role in the effects of psilocybin on brain and behavior.