Annals of the New York Academy of Sciences
August 1, 2006
Jerrold S. Meyer, Matthew E. Brevard, Brian J. Piper et al.
40 citations
A recreational dose of MDMA (1 mg/kg) activates multiple brain regions in marmoset monkeys, including the midbrain raphe nuclei, hippocampus, hypothalamus, amygdala, and the corticostriatal circuit (dorsal thalamus, sensory motor cortex, and basal ganglia). MDMA also activates the primary visual cortex and enhances the visual cortical response to light. The onset of brain activation matches the rise in plasma MDMA levels. A second study found that both low (4 × 1 mg/kg oral) and high (4 × 10 mg/kg intramuscular) MDMA doses reduce the NAA/creatine ratio in the hypothalamus, indicating vulnerability to damage. High doses also cause prolonged hyperthermia and reductions in serotonin and serotonin transporters in several brain areas, suggesting even recreational doses may have adverse consequences.
Frontiers in Neuroscience
May 1, 2025
Evan Fuini, Arnold Chang, Josh Edwards et al.
6 citations
Psilocybin, a hallucinogen, produces dose-dependent increases in brain activity in awake rats, particularly in the somatosensory cortex, basal ganglia, and thalamus. Female rats showed greater activation than males at the 0.3 mg/kg dose in thalamic and basal ganglia regions. The drug also caused a global increase in functional connectivity, especially hyperconnectivity to the cerebellum. Higher doses activated circuits involved in sensory filtering and motor organization, such as the cortico-striato-thalamo-cortical circuit and claustrum. However, the direction of BOLD signal changes and neural network activity patterns differed from those reported in human studies.
Neuropsychopharmacology
February 18, 2026
Itishree Sahoo, Sairam Masadi, Ashwath Maheswari et al.
3 citations
Adolescent mice given psilocybin every other day from postnatal days 40-50 showed long-term changes in brain structure and function when tested in adulthood. Brain imaging revealed reduced volume and altered water diffusivity in several regions, with males more affected than females. Functional connectivity increased globally and regionally, notably between the prefrontal cortex and hypothalamus, thalamus, and midbrain. Mice showed reduced brain sensitivity to rewarding and aversive odors, and males had lower levels of epigenetic and neuroplasticity protein markers in the prefrontal cortex. Behaviorally, female mice showed reduced mobility in the open field test, while no differences appeared in the light/dark box test. These findings indicate that adolescent psilocybin exposure produces lasting developmental consequences, especially in males.
bioRxiv (Cold Spring Harbor Laboratory)
February 6, 2025
Bryce Axe, Ashwath Maheswari, Reagan Walhof et al.
3 citations
preprint
Repetitive mild head injuries from sports, accidents, or military service cause lasting cognitive, motor, and behavioral problems and raise the risk of dementia, Parkinson's disease, and chronic traumatic encephalopathy, yet no approved treatment exists. Testing the psychedelic psilocybin in adult female rats with mild repetitive head injury, the authors report that psilocybin reduces vasogenic edema, restores normal vascular reactivity and functional connectivity, reduces buildup of phosphorylated tau, increases levels of brain-derived neurotrophic factor and its receptor TrkB, and modulates lipid signaling molecules. These findings suggest psilocybin may have healing effects on head injury-related brain damage.
Neuropharmacology
March 6, 2026
Noah Cavallaro, Priya Rai, David Akins et al.
1 citation
In a first-ever fMRI study of 5-MeO-DMT, a fast-acting psychedelic, brain activity changes were observed that match its quick onset and short peak effects. A previously unknown sex difference in how the brain responds to the drug was also identified. The findings align with the drug's unique pharmacology and clinical reports, offering new insights into its neural effects.
Frontiers in Psychiatry
April 13, 2026
Craig F. Ferris
Psychiatric drug development has stagnated for decades, with treatments for depression, schizophrenia, and PTSD offering only partial relief—remission rates of 30-40% for treatment-resistant depression and 60-70% of schizophrenia patients experiencing persistent symptoms. A paradigm shift proposes that mental illness stems from breakdowns in the brain's sensory filtering mechanisms, which gate irrelevant stimuli. The cerebellum is identified as a critical hub for bottom-up sensory gating, housing over half the brain's neurons and showing disrupted connectivity during PTSD symptom provocation. Psychedelic drugs may recalibrate these filters by disrupting entrenched filtering architectures and reopening plasticity windows. This framework extends predictive processing theory with a specific neural substrate and suggests novel therapeutic targets.