A single psychedelic dose of ketamine (1 mg/kg, intravenous) alters brain chemistry and connectivity in healthy people for at least one to eight days. After the dose, glutamate levels in the anterior cingulate cortex rose significantly. Functional connectivity decreased within high-order networks such as the default mode network, while integration between low- and high-order networks increased. Increases in a PET marker of synaptic plasticity correlated with reduced intrinsic activity in default mode network regions and a diminished influence of the posterior cingulate cortex on global network dynamics. The posterior cingulate cortex appears to be a central hub through which ketamine may reshape brain hierarchies over the long term.
A single intravenous dose of ketamine (1 mg/kg) in eleven healthy men altered brain chemistry and connectivity days later. Glutamate levels rose in the anterior cingulate cortex (ACC). Functional coupling between the ACC and the dorsolateral prefrontal cortex decreased, while coupling between the ACC and the amygdala increased. Participants whose PET scans indicated increased synaptic plasticity showed reduced intrinsic activity in default mode network (DMN) regions. The findings suggest the DMN is a central hub where ketamine may reshape brain hierarchies, offering clues to its therapeutic mechanisms.
Only 1.8% of people with substance use disorders receive effective treatment, revealing a gap between neuroscience research and clinical care. This paper argues that addiction neuroscience should shift from a diagnostic focus to a theragnostic framework that uses biomarkers to guide treatment decisions. Integrating fMRI, EEG, and PET biomarkers within psychedelic addiction research offers an opportunity for this change. Psychedelics like psilocybin engage neuroplasticity and reward networks central to addiction. The authors review neuroimaging paradigms for indexing drug effects and propose a roadmap for embedding biomarkers in clinical trials. They outline ongoing work at Imperial College London co-developing biomarkers for gambling and opioid use disorders to identify biotype-specific responses, aiming for regulatory-grade tools similar to those in oncology.