Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology – November 01, 2020
Source: PubMed
Summary
Psilocybin, a psychedelic substance, significantly alters brain glutamate levels, influencing how individuals experience their sense of self. In a study involving 30 participants, those with higher medial prefrontal cortical glutamate experienced negative ego dissolution, while lower levels in the hippocampus correlated with positive experiences. These findings highlight the complex neurobiological mechanisms at play and suggest that understanding glutamate's role could enhance therapeutic applications for depression and related disorders. This research sheds light on potential pathways for effective treatments in ongoing clinical trials.
Abstract
There is growing interest in the therapeutic utility of psychedelic substances, like psilocybin, for disorders characterized by distortions of the self-experience, like depression. Accumulating preclinical evidence emphasizes the role of the glutamate system in the acute action of the drug on brain and behavior; however this has never been tested in humans. Following a double-blind, placebo-controlled, parallel group design, we utilized an ultra-high field multimodal brain imaging approach and demonstrated that psilocybin (0.17 mg/kg) induced region-dependent alterations in glutamate, which predicted distortions in the subjective experience of one's self (ego dissolution). Whereas higher levels of medial prefrontal cortical glutamate were associated with negatively experienced ego dissolution, lower levels in hippocampal glutamate were associated with positively experienced ego dissolution. Such findings provide further insights into the underlying neurobiological mechanisms of the psychedelic, as well as the baseline, state. Importantly, they may also provide a neurochemical basis for therapeutic effects as witnessed in ongoing clinical trials.