Quality in Sport
January 31, 2026
Anna Maria Komarczewska, Filip Matusiak, Klaudia Brzoza et al.
Psilocybin-assisted interventions produce rapid reductions in depressive symptoms that can persist for months, including six-month outcomes in treatment-resistant depression protocols with psychological support. Convergent evidence from animal studies shows structural synaptic remodeling in frontal cortex and hippocampal plasticity changes in extinction learning paradigms. Human neuroimaging reveals altered large-scale brain dynamics after psilocybin. These findings support neuroplasticity as a biologically plausible mechanism linking transient serotonergic receptor activation to sustained clinical improvement.
Translational psychiatry
January 29, 2026
Rafael V Lima Da Cruz, Rêmullo B G de Miranda Costa, Gabriel M De Queiroz et al.
2 citations
A single dose of the psychedelic DMT reversed depression-like behavior and restored cognitive performance in male mice exposed to chronic stress, outperforming chronic fluoxetine across most measures. When given during the stress period, DMT reduced anhedonia but did not rescue cognitive deficits, indicating domain-specific long-lasting effects. All DMT regimens increased the integration of adult-born granule cells and reduced abnormally integrated cells in the brain, suggesting structural circuit repair. The role of the psychedelic experience remains uncertain because isoflurane anesthesia may have confounded results.
Zenodo (CERN European Organization for Nuclear Research)
January 26, 2026
Fernando Mora López, Johynny Solís Solís, Ekaterina Daniela Hernández Baker et al.
Psilocybin, acting as a 5-HT2A receptor agonist, alters brain connectivity in networks involved in self-referential processing and emotional regulation, accompanied by neuroplastic changes such as enhanced synaptogenesis and functional reorganization. Neuroimaging shows reduced amygdala activity and modifications in default mode and executive networks. Clinical evidence indicates substantial reductions in depressive symptoms, with meta-analyses reporting large effect sizes and durable benefits lasting from weeks to a year. Randomized controlled trials show rapid onset and higher remission rates than conventional treatments, even in treatment-resistant depression. Adverse events are mild, transient, and predictable, though methodological limitations like small samples and high heterogeneity call for larger Phase III trials.
Neuroscience
January 22, 2026
Guilherme Lodetti, Gislaine Zilli Réus, Eduardo Pacheco Rico
Fewer than half of patients with major depressive disorder achieve remission with standard pharmacotherapy, and many cannot tolerate it. This narrative review examines classic psychedelics as an alternative treatment. These substances primarily bind to 5-HT2A receptors, increasing connectivity between sensory and motor brain networks. They generate long-term behavioral responses comparable to traditional antidepressants. Clinical and experimental studies show that classic psychedelics alleviate depressive symptoms. The mood improvement is thought to stem from effects on neuroplasticity, including neurogenesis and related signaling pathways.
ACS chemical neuroscience
January 21, 2026
Miguel Salfiti, Marios Kyriazis, Georgios Mikellides
2 citations
Zalsupindole, a non-hallucinogenic psychoplastogen, promotes neuritogenesis and dendritic spine growth via 5-HT2-dependent mechanisms, potentially involving the mTOR pathway. In rats, it shows rapid brain penetration, no 5-HT2B agonism, no glutamate surge, and no head-twitch response. Single doses produce rapid and durable antidepressant-like effects in forced swim test and VMAT2-deficient mouse models. Phase 1 trials (2-360 mg) show good tolerability, no psychotomimetic effects, linear absorption, and dose-dependent EEG changes indicating synaptic potentiation. This biased 5-HT2A agonist may offer a new treatment for mood disorders without hallucinogenic side effects.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University
January 20, 2026
Ke Xia, Tianming Gao
Classic psychedelics, especially psilocybin, show promise for treating depression, with several randomized controlled trials indicating that one or a few sessions of psychedelic-assisted psychotherapy can produce rapid and lasting antidepressant effects in patients with treatment-resistant depression. Mechanistically, these substances quickly increase neurotrophic factors, enhance neuroplasticity, and reorganize brain networks, creating a window for psychotherapy. However, the specific molecular and circuit-level mechanisms remain unclear, with debate between the 5-HT2A receptor-dependent hypothesis and the TrkB neurotrophic pathway-dependent hypothesis. Key challenges include psychedelic-related risks, incomplete mechanistic understanding, lack of standardized protocols, and insufficient long-term safety data.
Zenodo (CERN European Organization for Nuclear Research)
January 19, 2026
Ngo Cheung
1 citation
Antidepressants that target different brain pathways—glutamatergic (ketamine-like), monoaminergic (SSRI-like), and GABAergic (neurosteroid-like)—vary in how quickly they work, how long effects last, and the risk of triggering mania, especially in people with bipolar disorder. A computer model simulating depression showed that while all three restored normal performance initially, the ketamine-like approach rebuilt neural connections, leading to better resilience under extreme stress and no manic relapse after stopping treatment. The neurosteroid-like approach worked rapidly but caused relapse in 88.3% of cases when discontinued. The SSRI-like method was slowest, showed the highest risk of mania, and led to 95.0% relapse after cessation. These results suggest that selecting antidepressants based on their mechanism could improve safety and long-term outcomes.
Journal of Psychopharmacology
January 6, 2026
Connor J. Maltby, Adam K. Klein, Enya Paschen et al.
3 citations
Psilocybin produces rapid and sustained antidepressant effects in major depressive disorder, but the underlying neurobiological mechanisms are unclear. In mice, psilocybin caused dose-dependent occupancy of the 5-HT₂A receptor in the prefrontal cortex, with an inverted-U dose-response for head twitch behavior peaking between 44% and 62% receptor occupancy. A 1.5 mg/kg dose increased time spent in open areas of the elevated zero maze, indicating reduced anxiety, while 3 mg/kg reduced immobility in the forced swim test, suggesting antidepressant-like effects. Both doses shifted α-tubulin post-translational modifications toward more dynamic microtubules and selectively increased synaptic protein expression in the prefrontal cortex, but not the amygdala. These findings indicate that psilocybin's therapeutic effects may involve dose- and region-specific enhancement of neuronal plasticity, with distinct signatures for anxiolytic-like and antidepressant-like properties.
OPUS FAU - Online publication system of Friedrich-Alexander-Universität Erlangen-Nürnberg
January 1, 2026
Aneta Petrušková
Serotonergic psychedelics LSD, psilocin, and DMT inhibit neurotransmission by reducing the proportion of synaptic vesicles that fuse in response to electrical stimulation after 3–30 minutes of treatment, an effect that disappears after 24 hours. DMT and psilocin increase evoked responses at glutamatergic synapses following single stimulation, while psilocin decreases paired-pulse facilitation. LSD and psilocin reduce evoked presynaptic calcium transients. At the network level, LSD and DMT strongly inhibit spontaneous neuronal firing without altering evoked responses. These findings expand understanding of the acute synaptic effects of psychedelics, though the link to therapeutic outcomes requires further research.
Frontiers in neuroscience
January 1, 2026
Marcos Lago, Mariana Cerveira, Joe Xavier Simonet
1 citation
A single case report describes an 80-year-old woman with a 10-year history of Alzheimer's disease and severe functional decline who showed temporary improvements in multiple domains after taking 5 grams of psilocybin-containing mushrooms. Before the intervention, she had urinary incontinence, difficulty walking, minimal speech, and required help with daily activities. About 19 hours after administration, she began speaking spontaneously about her life. Over the following days and weeks, she regained bladder control, walked better, dressed herself, showed more emotion, engaged in conversations, and recalled recent social interactions. The authors suggest that some functional capacity may persist even in late-stage Alzheimer's and can become temporarily accessible under certain conditions, but the findings do not indicate disease reversal.
Frontiers in pharmacology
January 1, 2026
Patricio Sáez-briones, Amanda Silva-Rodríguez, Michelle Morales-Vidal et al.
MDMA (Ecstasy) suppressed helping behavior in adult male rats at doses of 5 mg/kg and 10 mg/kg, fully eliminating the behavior, while lower doses (1 mg/kg and 0.5 mg/kg) caused partial inhibition only after the rats switched roles. The lowest dose (0.25 mg/kg) had no effect. Electrophysiological recordings showed that MDMA reinforced long-term depression in the nucleus accumbens core and increased long-term potentiation in the anterior cingulate cortex, with the latter depending on serotonin and oxytocin. These neuroplastic effects align with mechanisms thought to promote prosocial behavior, yet the drug disrupted helping behavior, suggesting MDMA may impair neural processes essential for executing helping actions without reducing the willingness to help.