Neuroscience & Biobehavioral Reviews
April 4, 2025
Claudio Agnorelli, Kate Godfrey, Gabriela Sawicka et al.
32 citations
Classic psychedelics (LSD, psilocybin, N,N-DMT) and non-classic psychedelics (ketamine, MDMA) enhance neuroplasticity—the nervous system's ability to adapt—through molecular, structural, and functional changes. Animal studies indicate these drugs induce meta-plasticity (heightened sensitivity to environmental stimuli) and hyper-plasticity (re-opening developmental windows for long-term structural changes), with implications for mood and behavior. Translating these findings to humans faces challenges due to limitations in current imaging techniques, but promising new directions include novel PET radioligands, non-invasive brain stimulation, and multimodal approaches. This review informs the development of targeted interventions for neuropsychiatric disorders.
arXiv (Cornell University)
November 29, 2024
Claudio Agnorelli, Meg J. Spriggs, Kate Godfrey et al.
2 citations
Classic psychedelics (LSD, psilocybin, N,N-DMT) and non-classic psychedelics (ketamine, MDMA) enhance neuroplasticity, the nervous system's ability to adapt. Animal studies indicate these drugs induce meta-plasticity, heightening sensitivity to environmental stimuli, and hyper-plasticity, reopening developmental windows for long-term structural changes that affect mood and behavior. Translating these findings to humans is challenged by limitations in current imaging techniques, but emerging approaches like novel PET radioligands, non-invasive brain stimulation, and multimodal methods offer promising directions. This review informs development of targeted interventions for neuropsychiatric disorders and advances understanding of psychedelics' therapeutic potential.
Br J Psychiatry
July 8, 2026
Hannah M. Douglass, Meg J. Spriggs, Kate Godfrey et al.
In a small pilot study, 21 women with anorexia nervosa received three doses of psilocybin (COMP360) over six weeks, combined with talk therapy and usual care. The treatment was well tolerated; common side effects were headache, nausea, and dizziness. Two serious adverse events (suicide attempts) occurred in one participant during the 6–12 month period. Eating disorder symptoms significantly improved at six months, and motivation to change improved at twelve months, though individual responses varied widely. The findings provide preliminary support for the feasibility and safety of psilocybin therapy in this population, but larger, more rigorous studies are needed.
bioRxiv Preprint Server
May 1, 2025
Claudio Agnorelli, Joseph Peill, Gabriela Sawicka et al.
preprint
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.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
March 21, 2026
Claudio Agnorelli, Joseph Peill, Gabriela Sawicka et al.
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.
arXiv Preprint Archive
November 29, 2024
Claudio Agnorelli, Meg Spriggs, Kate Godfrey et al.
Psychedelics like LSD and psilocybin can rewire brain connections after just one dose, unlike traditional psychiatric medications. These compounds boost the brain's natural plasticity, helping neurons form new pathways and adapt to change. Studies show they create a window of enhanced learning and adaptation, leading to lasting improvements in mood and behavior.