Brain Communications
January 1, 2024
Ashley Ghaw, Alisha Chunduri, Arnold Chang et al.
13 citations
Lysergic acid diethylamide (LSD) produced a dose-dependent increase in negative blood oxygen level-dependent (BOLD) signal, indicating decreased brain activity, in awake rats. The most affected regions were the primary olfactory system, prefrontal cortex, thalamus, and hippocampus. Contrary to the hypothesis that LSD would increase activity in the prefrontal cortex and thalamus while decreasing hippocampal activity, the results showed an acute decrease in activity across these areas. However, functional connectivity increased between the thalamus and somatosensory cortex, and between the cerebellar nuclei and surrounding brainstem areas. The enhanced thalamus-sensorimotor connectivity aligns with human studies, while the unexpected increase in cerebellar nuclei connectivity raises questions about its role in hallucinogenic effects.
Scientific Reports
August 11, 2024
Lila Harris-Blum, Zachary Smith, Richard J. Ortiz et al.
9 citations
Exposure to LSD during periadolescence in mice altered gray matter microarchitecture across much of the brain, particularly in the thalamus, sensory and motor cortices, and basal ganglia, while the forebrain olfactory system, prefrontal cortex, and hindbrain were unaffected. Multiple doses reduced functional connectivity between forebrain white matter tracts and sensorimotor cortices and hippocampus. However, no differences in brain volume, cognitive performance, or motor behavior were observed when the animals were tested as young adults. The pronounced changes in diffusion-weighted imaging values across 74 brain areas suggest altered neuroplasticity, but the behavioral consequences of the connectivity changes remain unknown.
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.
Neuroscience Bulletin
May 21, 2026
Noah Cavallaro, Priya Rai, David Akins et al.
Mescaline, a psychedelic used ceremonially for thousands of years, produces distinct brain effects that differ from LSD and psilocybin. In awake rats, mescaline suppressed BOLD signal in the cerebellum, suggesting it disconnects this region from forebrain areas. However, resting-state scans showed the cerebellum became hyperconnected to the hippocampus, thalamus, somatosensory cortex, and midbrain. Mescaline also eliminated normal brain responses to rewarding smells, indicating disrupted sensory processing. Acoustic startle tests revealed frequency-dependent effects: enhancement at 4 kHz (+27.6%) and 20 kHz (+27.3%), but impairment at 12 kHz (-16.4%). The cerebellum may act as a dysregulated sensory filter, flooding forebrain circuits with unprocessed information, potentially explaining psychedelic-induced perceptual changes.
Frontiers in Pharmacology
January 1, 2024
Jack M Ognibene, Rajeev I Desai, Praveen P Kulkarni et al.
Mice exposed daily to vaporized cannabis (10.3% Δ9-THC) for ten days showed a blunted brain response to Adderall, with decreased positive and increased negative BOLD signals in regions including the prefrontal cortex, accumbens, ventral pallidum, caudate/putamen, and thalamus. After a two-week washout without cannabis, the difference in Adderall response between cannabis-exposed and placebo groups disappeared. The findings suggest that short-term daily cannabis inhalation, comparable to recreational use, reduces sensitivity to the psychostimulant Adderall, particularly in dopaminergic circuitry, raising concerns about potential escalation of psychostimulant use.