Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin.
Natasha L MasonKim Paula Colette KuypersF MüllerJohannes T ReckwegD H Y TseStefan W ToennesN R P W HuttenJ F A JansenP StiersA FeildingJ G RamaekersPublished in: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (2020)
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.
Keyphrases
- clinical trial
- high resolution
- drug induced
- cerebral ischemia
- depressive symptoms
- liver failure
- placebo controlled
- emergency department
- working memory
- oxidative stress
- squamous cell carcinoma
- phase ii
- photodynamic therapy
- high glucose
- drinking water
- mass spectrometry
- study protocol
- bone marrow
- phase ii study
- brain injury
- open label
- rectal cancer
- electronic health record
- aortic dissection
- temporal lobe epilepsy