JAMA Psychiatry
December 7, 2022
Joshua S. Siegel, James E. Daily, Demetrius A. Perry et al.
168 citations
Between 2019 and 2022, 25 U.S. states considered 74 bills related to psychedelic drugs, with 10 enacted and 32 still active. The number of bills introduced each year rose from 5 in 2019 to 36 in 2022. Most bills (90%) specified psilocybin, and 58% proposed decriminalization, though few included medical oversight or licensure requirements. Early legislative efforts occurred in liberal states, but the partisan gap has narrowed, suggesting reform is becoming bipartisan. An analytic model based on marijuana legalization projects that a majority of states will legalize psychedelics by 2034 to 2037.
Psychopharmacology
January 22, 2021
J. Siegel, B. Palanca, B. Ances et al.
53 citations
A single 96-hour infusion of ketamine, co-administered with clonidine, is well tolerated and produces a rapid and sustained antidepressant response in over 50% of adults with treatment-resistant depression. In an open-label study of 23 adults, depressive symptoms dropped markedly from an average MADRS score of 29 at baseline to 9 one day after infusion, and remained reduced at 2 weeks (13) and 8 weeks (15). Brain imaging showed that the infusion normalized overconnectivity in the limbic system and between the subgenual anterior cingulate cortex and the default mode network, with response-dependent and treatment-dependent connectivity changes.
medRxiv
August 24, 2023
Subha Subramanian, Demetrius Perry, Caterina Gratton et al.
14 citations
preprint
Psilocybin disrupts connectivity across cortical networks and subcortical structures, producing more than three-fold greater acute changes in functional networks than methylphenidate. These changes are driven by desynchronization of brain activity across spatial scales, strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self. Performing a perceptual task reduces psilocybin-induced network changes, suggesting a neurobiological basis for grounding during psychedelic therapy. Psilocybin induces a persistent decrease in functional connectivity between the anterior hippocampus and cortex (and DMN in particular), lasting for weeks but normalizing after six months. This persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for psilocybin's pro-plasticity and anti-depressant effects.
Nature Neuroscience
October 13, 2025
Jonah A. Padawer-Curry, Oliver J. Krentzman, Chao‐cheng Kuo et al.
9 citations
Psychedelics like psilocybin and DOI alter the brain's hemodynamic response, potentially disrupting the normal coupling between neuronal activity and blood flow. In human fMRI scans, psilocybin induced changes in hemodynamic response functions. In awake mice, DOI differentially affected the relationship between cortical excitatory neuronal activity and hemodynamic signals, both during whisker stimulation and at rest, leading to discordant changes in functional connectivity measures depending on whether they were based on neuronal or hemodynamic data. A selective serotonin-2A receptor antagonist reversed many of these effects. The findings indicate that the vasoactive effects of psychedelics must be considered when interpreting blood-based measures of brain function.
bioRxiv (Cold Spring Harbor Laboratory)
September 24, 2023
Xiaodan Wang, Jonah A. Padawer-Curry, Oliver J. Krentzman et al.
9 citations
preprint
Psychedelics show promise for treating mood disorders, but their effects on brain blood vessels have been overlooked. Psilocybin altered hemodynamic response functions in humans, suggesting changes in neurovascular coupling (NVC). Using wide-field optical imaging in awake mice, the psychedelic DOI (a serotonin-2A receptor agonist) partially altered task-based NVC but caused more pronounced NVC changes during rest, especially in association brain regions. Calcium and hemodynamic signals gave different accounts of resting-state functional connectivity under DOI. Co-administration with a 5-HT2A antagonist reversed many effects. The dissociation between neuronal and hemodynamic signals highlights the need to consider neurovascular effects when interpreting fMRI measures in psychedelic studies.
Scientific Data
June 5, 2025
Subha Subramanian, Travis Rick Renau, Demetrius Perry et al.
4 citations
A psychedelic drug, psilocybin, and a comparison drug, methylphenidate, produce distinct acute and persistent changes in brain networks measurable with precision functional mapping, a technique that improves signal detection by repeatedly scanning individuals. Seven healthy adults underwent extensive baseline brain imaging, imaging shortly after drug intake, and follow-up scans for up to two weeks. Four participants repeated the psilocybin protocol months later. The dataset includes resting-state and task-based functional MRI, structural scans, and subjective experience reports. The authors release this resource to help researchers study how psilocybin and methylphenidate alter brain network organization over time.
Biological Psychiatry
April 29, 2024
Joshua S. Siegel, Subha Subramanian, Nico U.f. Dosenbach et al.
3 citations
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