Biomedicines
February 25, 2026
Alice Melani, Giorgia Papini, Marco Bonaso et al.
Psychedelics are gaining renewed scientific interest as breakthrough therapies for mental disorders, with ayahuasca and its active component DMT showing particular promise. DMT acts primarily as a serotonin 5-HT2A receptor partial agonist, while 5-MeO-DMT has higher affinity for 5-HT1A receptors; both foster neuroplasticity and reorganize brain networks involved in perception, cognition, and mood. Current evidence offers an optimistic outlook for treatment-resistant depression and major depressive disorder, with four phase II studies of 5-MeO-DMT and one of DMT for TRD, plus two phase II studies of DMT fumarate for MDD. Evidence for other mental disorders remains preliminary.
Translational Psychiatry
February 19, 2026
Luís Carlos Pereira, Wigínio Gabriel Lira-Bandeira, Andréa Silva Medeiros-Bandeira et al.
Chronic stress from social isolation in juvenile male marmosets reduces neuronal volume in the somatosensory cortex, a brain region implicated in depression. Ayahuasca, a psychedelic brew, given before and during isolation prevented this reduction, with treated animals showing neuronal volumes similar to non-stressed controls. Trends also suggested preserved cortical structure, though differences in neuronal density and overall cortical volume were not statistically significant. These results indicate ayahuasca may protect against stress-induced cortical atrophy and support further research into its therapeutic potential for stress-related psychiatric disorders, especially in adolescents.
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.
Translation The University of Toledo Journal of Medical Sciences
February 17, 2026
Amy Hooper, Evelyn K. Lambe
MDMA-assisted psychotherapy shows promise for PTSD, especially when standard treatments like SSRIs and trauma-focused cognitive behavioral therapy have failed. A review of evidence from human and rodent studies examines two main explanations for its effects: a neurobiological model, where MDMA reduces amygdala reactivity, boosts hippocampal connectivity, and alters serotonin and oxytocin signaling to aid fear extinction, memory reconsolidation, and neuroplasticity; and a relational model, where MDMA's prosocial and empathogenic qualities strengthen the therapeutic alliance and patient suggestibility. Rather than being mutually exclusive, these processes likely work together, with MDMA creating a "window of emotional safety" that enables both neurobiological and interpersonal healing. Understanding this dual action is key to refining treatment protocols and therapist training.
Pharmaceuticals
February 14, 2026
Petra Dolenec, Goran Pelčić, Kristina Pilipović et al.
Glaucoma is an ischemic neurodegenerative disease driven not only by high eye pressure but also by vascular, metabolic, and inflammatory damage that progressively disconnects retinal neurons from the brain. Current treatments lower eye pressure but do not address this neurodegeneration or restore lost connections. Ischemia triggers excitotoxicity, oxidative stress, and chronic inflammation involving microglia and astrocytes, which suppress the brain's natural ability to repair itself. Psychoplastogens—compounds like ketamine, psilocybin, and DMT—rapidly enhance structural and functional neuroplasticity through BDNF-TrkB-mTOR signaling and also exert anti-inflammatory effects. This review integrates insights from cerebral ischemia to propose psychoplastogens as potential neurorestorative and anti-inflammatory agents for glaucoma, while outlining translational challenges.
Acta Neuropsychiatrica
February 13, 2026
Tanya Calvey, D. Govender, Gavin Owen et al.
Ibogaine, a psychedelic alkaloid with no approved medical use, has been linked in observational studies to symptom relief for substance use disorder, multiple sclerosis, and traumatic brain injury after a single dose. This review examines the neurobiological mechanisms behind these effects, focusing on remyelination and metabolic restoration. Evidence indicates ibogaine increases markers of myelination after opioid administration, and that these disorders involve white matter pathology and disrupted metabolic homeostasis, ischemia, and hypoxia. The authors conclude that ibogaine's multi-receptor actions—particularly on NMDA, kappa opioid, and sigma receptors—reduce excitotoxicity, regulate metabolism, promote lasting neuroplasticity, and modulate immunity, facilitating neuronal repair and remyelination, supporting further research as a therapeutic agent for these central nervous system disorders.
Neuropsychopharmacology
February 13, 2026
Fabrizio Ascone, Valeria Buzzelli, Francesca Mottarlini et al.
2 citations
In a rat model of Fragile X Syndrome (FXS), psilocybin microdosing rescued deficits in novel object recognition memory. This benefit persisted even when serotonin receptors (5HT2AR or 5HT1AR) were blocked, but was abolished by blocking the TrkB receptor, indicating that the effect depends on BDNF/TrkB signaling rather than classical serotonergic pathways. At the molecular level, psilocybin normalized mature BDNF, increased TrkB, and restored downstream AKT signaling in the prefrontal cortex—pathways linked to synaptic plasticity and cognition. These results suggest psilocybin microdosing could be a promising therapeutic strategy for neurodevelopmental disorders like FXS and autism spectrum disorder, potentially dissociating therapeutic benefits from hallucinogenic effects.
Preprints.org
February 9, 2026
Philippe Henry
preprint
A novel treatment approach for treatment-resistant depression and chronic anxiety combines the rapid neuroplastic effects of the psychedelic 5-MeO-DMT with the anxiolytic properties of the cannabinoid THCV, delivered via a precision vaporization device. The THCV acts as a 'cushion' to prevent the panic and acute activity increase often triggered by high-potency psychedelics, while allowing the tryptamine to promote synaptic growth and reset the Default Mode Network. This synergistic combination aims to provide more effective and tolerable relief than existing antidepressants, which require weeks to work and do not address synaptic atrophy.
Zenodo (CERN European Organization for Nuclear Research)
February 6, 2026
Zen Revista
Psilocybin, a psychedelic compound, triggers activity-dependent rewiring of large-scale cortical networks. Using monosynaptic rabies viral tracing in mice, researchers mapped brain-wide inputs to pyramidal neurons in the dorsal medial frontal cortex. Psilocybin strengthened pathways routing sensory and retrosplenial inputs to subcortical targets while weakening cortico-cortical recurrent loops. This reorganization depends on neural activity during drug administration, shown through chemogenetic silencing. These findings offer insights into psychedelic mechanisms and suggest combining targeted neuromodulation with psychedelic treatment to enhance therapeutic outcomes for mental health disorders.
Molecular Psychiatry
February 3, 2026
Pablo Mallaroni, S. Parker Singleton, Natasha L. Mason et al.
The psychedelic phenethylamine 2C-B produces less dysphoria and subjective impairment than the tryptamine psilocybin. In 22 healthy volunteers, 7 Tesla resting-state functional MRI mapped acute effects of matched doses of 20 mg 2C-B, 15 mg psilocybin, and placebo. Both compounds selectively reduced intranetwork static functional connectivity while broadly increasing between-network and subcortical-cortical connectivity. Compared to psilocybin, 2C-B showed less pronounced reductions in between-network dynamic connectivity variability but elevated transmodal static connectivity. Both increased brain complexity similarly. PET density modeling linked neural effects to differences in monoaminergic transporter and serotonergic receptor binding beyond 5-HT2A. Behavioral markers of psychedelic effects reflected decoupling of the transmodal axis of functional brain organization.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
February 1, 2026
Isabel Werle, Francisco S Guimarães, Rafael G Dos Santos et al.
Ayahuasca, a brew containing the psychedelic DMT, helps rodents overcome persistent and generalized fear memories by boosting brain-derived neurotrophic factor (BDNF) signaling in the infralimbic (IL) region of the medial prefrontal cortex. In rats exposed to stress or high-intensity fear conditioning, repeated ayahuasca (0.3 mg/kg DMT) enhanced extinction learning and its retention, and reduced fear generalization. These effects were blocked by infusing an anti-BDNF antibody or a TrkB receptor antagonist into the IL cortex. The reduction in fear generalization depended on BDNF in females but not males. The findings suggest psychedelics may aid in treating difficult-to-extinguish trauma memories, such as those in PTSD.