Nature communications
October 3, 2022
S Parker Singleton, Andrea I Luppi, Robin L Carhart-Harris et al.
156 citations
Psychedelics like LSD and psilocybin temporarily alter subjective experience by acting on serotonin 2a (5-HT2a) receptors, increasing the diversity (entropy) of brain activity. This increase may arise from a flattening of the brain's control energy landscape. Using fMRI data, the authors show that these compounds reduce the control energy needed for transitions between brain states compared to placebo. Across individuals, lower control energy correlates with more frequent state transitions and higher entropy. Incorporating PET data on 5-HT2a receptor distribution under non-drug conditions, the analysis links these receptors to reduced control energy. The findings demonstrate that receptor-informed network control theory can model how neuropharmacological manipulation affects brain dynamics.
Nature communications
April 11, 2019
Ingvar R Möller, Marika Slivacka, Anne Kathrine Nielsen et al.
92 citations
The serotonin transporter (SERT) clears serotonin from the synapse, making it a key target for antidepressants and other drugs. Using hydrogen-deuterium exchange mass spectrometry, the authors mapped changes in SERT's shape and flexibility when it binds sodium and potassium ions, the neurotransmitter serotonin, and the drugs S-citalopram, cocaine, and ibogaine. Binding altered dynamics in specific structural regions: TM1, EL3, EL4, and TM12 for ions, and TM1, EL3, and EL4 for the other ligands. These results offer a direct view of how SERT responds to both natural substrates and pharmaceutical compounds, deepening understanding of its structure and function.
Nature communications
March 11, 2024
Andrea I Luppi, Lynn Uhrig, Jordy Tasserie et al.
43 citations
Loss of consciousness under anesthesia increasingly constrains brain activity to follow the brain's physical structure, collapsing hierarchical cortical organization across scales. This effect was observed with three different anesthetics—propofol, sevoflurane, and ketamine—and was reversed by electrically stimulating the central thalamus, which also restored behavioral signs of arousal. Stimulating the ventral lateral thalamus did not produce these effects, showing specificity. The findings identify distributed brain signatures of consciousness that are orchestrated by particular thalamic nuclei.
Nature communications
August 23, 2024
David H Sarrazin, Wilf Gardner, Carole Marchese et al.
41 citations
Depression involves disrupted circadian rhythms, but the role of internal clocks in mood-regulating brain areas was unclear. In a mouse model of depression, the medial prefrontal cortex (mPFC) showed increased expression of circadian negative-loop genes and decreased positive-clock regulators, and the rapid antidepressant ketamine counteracted these changes. Removing the clock gene Bmal1 from excitatory neurons prevented both depression-like behavior and ketamine's effects. Silencing the clock gene Per2 in mPFC produced antidepressant-like effects, while activating REV-ERB worsened depression and blocked ketamine. Boosting the clock activator ROR had antidepressant-like effects, increasing plasticity-related proteins and synaptic receptors in mPFC. The mPFC molecular clock critically regulates depression-like behavior, and targeting it therapeutically may influence glutamatergic plasticity.
Nature communications
May 9, 2024
Jacinthe Cataldi, Aurélie M Stephan, José Haba-Rubio et al.
32 citations
Incomplete awakenings from non-rapid eye movement sleep can produce sleepwalking and related behaviors, which sometimes involve conscious experience and later recall. Using high-density EEG and immediate interviews, the authors found that conscious experiences during these episodes (56% of cases) were preceded by high-amplitude slow waves in anterior brain regions and activation in posterior regions, patterns similar to those seen in dreaming. Recall of the experience (56% of cases) was linked to higher EEG activation in the right medial temporal area before movement. No conscious experience occurred in 19% of episodes, and no recall in 25%. These findings suggest that the brain activity underlying parasomnia experiences resembles that of dreams, pointing to core processes for sleep consciousness.
Nature communications
May 5, 2026
T Lyons, M Spriggs, L Kerkelä et al.
19 citations
A single high dose of psilocybin (25 mg) in 28 healthy, psychedelic-naive participants produced anatomical and functional brain changes lasting from one hour to one month. At one month, participants showed increased cognitive flexibility, psychological insight, and well-being. Diffusion tensor imaging revealed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity. Decreased modularity negatively correlated with increased well-being, consistent with depression findings. Increased cortical signal entropy one to two hours after dosing predicted improved well-being at one month, mediated by next-day psychological insight. No effects occurred with a 1 mg placebo dose.
Nature communications
September 20, 2024
Václav Havel, Andrew C Kruegel, Benjamin Bechand et al.
18 citations
A new class of iboga alkaloids, called oxa-iboga, was created by modifying the iboga molecular structure to replace a key component with a benzofuran ring. These compounds lack the heart rhythm risks (proarrhythmic effects) of ibogaine and noribogaine when tested on human heart cells. In male rats, oxa-iboga compounds were more effective than ibogaine at reducing opioid use. They act as potent kappa opioid receptor agonists but produce different behavioral effects than typical kappa agonists. A single dose or short treatment with oxa-noribogaine led to long-lasting reductions in morphine, heroin, and fentanyl intake, reversed persistent opioid-induced pain sensitivity, and suppressed drug-seeking behavior in relapse models. These compounds offer a mechanistically distinct approach to treating opioid use disorder.
Nature communications
June 22, 2024
Devin P Effinger, Jessica L Hoffman, Sarah E Mott et al.
15 citations
Psilocin, the psychoactive metabolite of psilocybin, increases activity in the paraventricular nucleus of the hypothalamus (PVN) in rats, a brain region central to stress response, autonomic function, and social behavior. In male rats, psilocin heightened PVN reactivity to an aversive air-puff stimulus, driven by active threat responders, while females showed no such increase. This effect was temporary, with reactivity returning to baseline 2 and 7 days after injection. Prior psilocin did not alter PVN reactivity during acute restraint stress. The findings identify the PVN as a key site of psychedelic action with implications for threat-related behavior.
Nature communications
August 13, 2025
William Wong, Rubén Herzog, Kátia Cristine Andrade et al.
10 citations
A new open database, the DREAM database, combines standardized sleep magneto/electroencephalography (M/EEG) recordings with dream reports from 505 participants across 20 datasets, totaling 2,643 awakenings. Each awakening includes at least 20 seconds of high-resolution sleep EEG (≥100 Hz, ≥2 electrodes) and a classification of the sleeper's reported experience. Analyses showed that reports of conscious experiences during sleep can be predicted from objective EEG features in both REM and NREM sleep. The database aims to overcome limitations of small sample sizes and methodological variability in dream research, enabling larger-scale investigations of the neurocognitive basis of dreaming.
Nature communications
November 20, 2025
Alaina M Jaster, Thomas M Hadlock, Belle Buzzi et al.
9 citations
A single dose of the psychedelic psilocybin reduces conditioned behavior and withdrawal caused by the opioid oxycodone in male mice but not in females. This sex-specific effect is mediated by the 5-HT2A receptor in frontal cortex pyramidal neurons that project to the nucleus accumbens. Psilocybin also alters epigenomic regulation after repeated oxycodone exposure and induces sex-specific structural plasticity in the nucleus accumbens independently of the 5-HT2A receptor. Female frontal cortex and nucleus accumbens show fewer changes at gene enhancer regions in response to psilocybin, repeated oxycodone, or their combination compared to males, with the frontal cortex displaying more pronounced sex differences at the epigenomic level.
Nature communications
August 15, 2024
Davor Curic, Donovan M Ashby, Alexander McGirr et al.
9 citations
Brain activity during quiet wakefulness exhibits scale-free patterns of coordinated neuronal firing, thought to reflect a universal operating mechanism. This study examined how three common anesthetics—isoflurane, pentobarbital, and ketamine—at multiple doses alter these patterns in the mouse cortex using calcium imaging. Low doses largely preserved scale-free statistics, but surgical-plane anesthesia disrupted critical avalanche dynamics, producing multiple abnormal modes. The findings reveal distinct pathways away from the default critical state, depending on the anesthetic and individual responses, suggesting a complex relationship between criticality and consciousness.
Nature communications
June 10, 2024
Andiara E Freitas, Bo Feng, Timothy Woo et al.
9 citations
A single low dose of ketamine produces both immediate and lasting antidepressant effects, linked to the repair of glutamatergic synapses in the medial prefrontal cortex. In a mouse model of chronic stress, ketamine altered multiple molecular pathways. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling decreased after chronic corticosterone treatment but increased after ketamine in most excitatory neurons. Similar PCP signaling reductions were predicted in the dorsolateral prefrontal cortex of people with major depressive disorder. Neurons connecting the infralimbic prefrontal cortex to the basolateral amygdala regulated immobility and food intake. Knocking out specific PCP proteins in these neurons blocked ketamine's synapse restoration and behavioral improvements, indicating that PCP proteins in this circuit mediate ketamine's effects.
Nature communications
March 22, 2025
Chunyan Meng, Wenting Guo, Chuan Xiao et al.
4 citations
Psilocybin, a compound from psychedelic mushrooms, shows promise for treating psychiatric conditions when used in therapy. A biosynthetic method could produce psilocybin quickly and efficiently, and understanding the enzymes involved can improve this process. Researchers determined the crystal structures of three key enzymes—PsiD, PsiK, and PsiM—in various forms, revealing how they work together to convert L-tryptophan into psilocybin. The structures show self-cleavage and self-inhibition mechanisms in PsiD and the stepwise catalytic sequence. Tests on female mice with depression-like behaviors demonstrated antidepressant effects from biosynthetic intermediates, particularly norbaeocystin, highlighting its clinical potential.
Nature communications
April 10, 2026
D P Effinger, J L Hoffman, S G Quadir et al.
1 citation
Psilocin, the active metabolite of psilocybin, alters brain activity in rats in a sex-specific manner. It increases activity in the paraventricular nucleus of the thalamus (PVT) and selectively engages PVT projections to the central amygdala (CeA) in females but not males. Psilocin enhances PVT reactivity to an aversive stimulus, driven by passive responders, and prevents time-dependent reductions in stimulus-evoked activity in PVT→CeA neurons in females but not males, driven by active responders. These findings identify sex-specific modulation of thalamic-limbic circuitry by psilocin, advancing understanding of how psychedelics modulate emotional brain circuits.
Nature communications
November 21, 2025
Marco Aqil, Gilles De Hollander, Nina Vreugdenhil et al.
Psilocybin changes how the brain processes visual context, altering perception of the Ebbinghaus illusion and modifying cortical responses to visual stimuli. A computational model links these changes, suggesting that psychedelics generally act by disrupting contextual computations in the brain.