iScience
May 19, 2023
Andres Ort, John W Smallridge, Simone Sarasso et al.
47 citations
Classical psychedelic drugs like psilocybin induce profound changes in consciousness, including heightened sensory-emotional awareness and arousal, accompanied by increased spontaneous EEG signal diversity. By combining Transcranial Magnetic Stimulation (TMS) with EEG, this work shows that psilocybin creates a state of increased chaotic brain activity, which is not due to altered complexity in causal interactions between brain regions. The study also maps regional effects of psilocybin on TMS-evoked activity, identifying changes in frontal brain structures that may relate to the phenomenology of psychedelic experiences.
iScience
April 9, 2024
Ram Harari, Ipsita Chatterjee, Dmitriy Getselter et al.
20 citations
Psilocybin and its metabolite psilocin produce psychedelic effects by activating the 5-HT2A receptor. While proposed as a treatment for depression and anxiety, psilocybin can also induce acute anxiety. In mice, psilocybin increased anxiety in behavioral tests. Blocking the 5-HT2A receptor reduced the head twitch response (a proxy for psychedelic effects) but did not prevent the anxiety-related behavior. Phosphopeptide analysis of the amygdala revealed signal transduction pathways both dependent and independent of the 5-HT2A receptor. Presynaptic proteins were specifically involved in psilocybin-induced acute anxiety. These findings suggest that anxiety and psychedelic effects involve separable mechanisms, informing clinical use.
iScience
May 17, 2024
Lluis Miquel-Rio, Unai Sarriés-Serrano, María Sancho-Alonso et al.
16 citations
Depression involves disruptions in the endoplasmic reticulum (ER) of serotonin neurons. In mice, artificially inducing ER stress in these neurons reduced Egr1-dependent serotonin activity and neurotransmission, leading to impaired neuroplasticity in forebrain regions and depressive-like behaviors. Ketamine reversed these effects by activating eIF2α signaling, which rapidly restored neuroplasticity. The findings identify ER stress in serotonin neurons as a cellular mechanism in depression and highlight eIF2α as a key target for ketamine's fast antidepressant action.
iScience
July 21, 2023
Haojie Li, Zhihao Du, Shunze Shen et al.
14 citations
Tai Chi, yoga, Yi Jin Jing, Five Animal Play, and Qigong Meditation each reduced depressive symptoms in college students, with Qigong Meditation showing the largest effect. Tai Chi, yoga, and Yi Jin Jing also lessened anxiety symptoms, with Yi Jin Jing producing the greatest improvement. All six mind-body exercise therapies were effective for improving anxiety and depression in this population.
iScience
January 17, 2025
Paolo Cardone, Arthur Bonhomme, Vincent Bonhomme et al.
9 citations
In a small double-blind, placebo-controlled, cross-over trial with three adults who had prolonged disorders of consciousness after a coma, an intravenous sub-anesthetic dose of the atypical psychedelic ketamine increased brain complexity as measured by Lempel-Ziv complexity, but did not change the explainable consciousness indicator. Patients showed reduced spastic paresis and spent more time with their eyes open, yet their diagnosis of consciousness did not improve. No adverse effects occurred. The findings suggest a potential therapeutic role for ketamine in disorders of consciousness and support a link between brain complexity and conscious states.
iScience
January 19, 2024
Hsin-Ping Wu, Estelle Nakul, Sophie Betka et al.
9 citations
Out-of-body experiences (OBEs) involve feeling located outside one's own body, often looking down from above. These experiences have been linked to disrupted integration of bodily signals, particularly visual and vestibular information. In two experiments using mixed reality and a motion platform, congruent visual-vestibular stimulation in a self-centered reference frame induced an OBE-like illusion in healthy participants, characterized by elevated self-location and feelings of disembodiment and lightness. The strength of this illusion varied with individuals' visual field dependency, measured by the Rod and Frame Test. The findings suggest that OBEs arise from a mismatch between visual and vestibular cues related to gravity and self-motion.
iScience
November 15, 2024
Lei Xie, Zelin Zhuang, Baowen Guo et al.
5 citations
Ketamine addiction in rats disrupts the microbiota-gut-brain axis (MGBA), leading to altered gut bacteria, damage to the intestinal lining, and changes in brain function. In a conditioned place preference model, ketamine-exposed rats showed reduced brain activity in the hippocampus, damaged hippocampal neurons, shortened ileum villi, and thinner colonic mucosa compared to controls. The abundance of specific gut bacteria correlated with addiction behavior, hippocampal activity, and intestinal damage. These findings suggest that MGBA abnormalities are part of ketamine addiction's mechanism, pointing to potential new treatment targets.
iScience
March 28, 2024
4 citations
Psychedelics are re-emerging as fast-acting treatments for mood and substance use disorders, but their cellular and molecular mechanisms remain unclear. Current research using murine neurons and immortalized cell lines has identified the serotonin 2A receptor as the primary driver of neuroplastic changes, yet these models fail to capture human- and disease-specific features. Incorporating human pluripotent stem cells (PSCs) can address this gap by differentiating into diverse brain cell types that mirror natural gene expression and disease phenotypes. Brain organoids derived from PSCs replicate cell diversity and regional patterning, enabling study of circuit-level changes. PSC-based models offer a promising approach to uncover the cellular and molecular basis of psychedelic-induced recovery in neuropsychiatric conditions.
iScience
January 16, 2026
Amir Valizadeh, John D Roache, Xinyu Zhang et al.
2 citations
Post-traumatic stress disorder varies greatly in its clinical and biological features, making treatment difficult. The largest randomized trial of ketamine for PTSD found no overall benefit over placebo, highlighting the need to identify which patients might respond. Using pre-treatment blood DNA methylation profiles and clinical data from that trial, machine learning models predicted treatment response. A model based on 1,208 methylation sites outperformed models using only clinical variables, and combining both data types improved accuracy further. The methylation-derived score identified responders with 92.9% accuracy. Predictive methylation sites were near genes involved in glutamatergic signaling, immune regulation, and known PTSD risk loci, suggesting peripheral DNA methylation patterns can guide precision pharmacotherapy for PTSD.
iScience
June 20, 2025
Michelle K Piazza, Abigael R Weit, Ege T Kavalali et al.
2 citations
Ketamine's antidepressant effects depend on increasing brain-derived neurotrophic factor (BDNF) and activating its receptor TrkB in the hippocampus. Rett syndrome, caused by MECP2 mutations, involves reduced BDNF. In Mecp2 knockout mice, ketamine and a TrkB agonist, LM22A-4, enhance both excitatory and inhibitory synaptic plasticity through separate BDNF-TrkB pathways. MeCP2 normally stabilizes inhibitory neurotransmission; without it, ketamine causes sustained disinhibition. These findings reveal how MeCP2 shapes acute ketamine action and suggest mechanisms for ketamine-based Rett syndrome treatments.
iScience
May 16, 2025
Shouyi Chen, Liurong Lin, Qian Zhou et al.
2 citations
Choking cough during emergence from anesthesia is common (15%-94%) and can cause severe discomfort, especially after neck surgery. Combining esketamine with remifentanil reduces the median effective concentration (EC50) of remifentanil needed to suppress cough during extubation in male patients undergoing anterior cervical spine surgery. The EC50 was 1.88 ng/mL with esketamine versus 2.55 ng/mL with remifentanil alone. No significant differences occurred in intraoperative hemodynamics or extubation time. Lower postoperative pain scores were observed at 2 and 24 hours. The combination effectively lowers the required remifentanil dose and reduces early pain, offering a reference for perioperative care.
iScience
May 19, 2024
Andres Ort, John W Smallridge, Erich Seifritz et al.
1 citation
Psilocybin, a serotonergic psychedelic being studied for psychiatric treatment, preserved reinforcement learning in a probabilistic cue-reward task using emotional faces presented consciously or subconsciously. Across dosages, psilocybin was statistically noninferior to placebo and suggested higher exploratory behavior. The 20 mg group showed significantly better learning rates than placebo. Psilocybin led to inferior learning with subconscious cues compared to placebo, but better results with conscious neutral cues in some conditions. The findings indicate that modulating serotonin signaling with psilocybin sufficiently preserves reinforcement learning.
iScience
April 15, 2026
Scheila Cristina Biazatti, Deborah Bambil, Rômulo Môra et al.
Machine learning analysis of morphological traits within a single plant species shows only partial agreement with traditional ethnobotanical classifications. Confusion matrix and similarity network analyses revealed that automated methods can validate folk taxonomies by detecting subtle variation, though they do not fully replicate previous classification systems. Integrating indigenous knowledge with computational approaches enables systematic assessment of how local communities categorize biological diversity.
iScience
February 21, 2026
Andrew D. Geoly, John P. Coetzee, Derrick Matthew Buchanan et al.
In a small study of 22 military veterans with traumatic brain injury, a single treatment with magnesium-ibogaine was associated with changes in brain structure one month later. Brain scans showed an average reduction in predicted brain age of 1.3 years, increased thickness in 11 cortical regions, and volume expansion in 8 subcortical regions. While the authors note that the imaging technique can also reflect nonstructural changes, the overall pattern of results is consistent with neuroplastic change.
iScience
November 21, 2025
Caleb Liang, Wen-Hsiang Lin, Wei-Kai Liou et al.
Healthy participants in virtual reality can experience owning and being located in two bodies simultaneously, a phenomenon called the Double Body Effect. In the experiments, participants wobbled involuntarily while watching two identical avatars performing the same movements. This effect occurred whether the avatars were seen from a first-person or third-person perspective. The findings indicate that body ownership and body location are more flexible than previously thought, and that self-location and body-location are distinct experiences. The results also suggest that the relationship between self and body is more complex than traditional dualism or contemporary reductionism, and may provide a preliminary model for understanding the puzzling experience of heautoscopy.