Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics?

European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 27, 2024

The growing interest in the rapid and sustained antidepressant effects of dissociative anesthetic ketamine classic psychedelics, such as psilocybin, is remarkable. However, both psychedelics are known to induce acute mystical experiences; can cause symptoms out-of-body experience, while typically bring about hallucinogenic experiences, like a profound sense unity with universe or nature. role these experiences enhancing outcomes for patients depression currently an area ongoing investigation debate. Clinical studies have shown that following administration (S)-ketamine (esketamine) not directly linked their properties. In contrast, potential (R)-ketamine (arketamine), thought lack side effects, has yet be conclusively proven large-scale clinical trials. Moreover, although activation serotonin 5-HT

Language: Английский

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Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6521 - 6521

Published: June 13, 2024

Glutamate is the main excitatory neurotransmitter in brain wherein it controls cognitive functional domains and mood. Indeed, areas involved memory formation consolidation as well fear emotional processing, such hippocampus, prefrontal cortex, amygdala, are predominantly glutamatergic. To ensure physiological activity of brain, glutamatergic transmission finely tuned at synaptic sites. Disruption mechanisms responsible for glutamate homeostasis may result accumulation excessive levels, which turn leads to increased calcium mitochondrial abnormalities, oxidative stress, eventually cell atrophy death. This condition known glutamate-induced excitotoxicity considered a pathogenic mechanism several diseases central nervous system, including neurodevelopmental, substance abuse, psychiatric disorders. On other hand, these disorders share neuroplasticity impairments areas, accompanied by structural remodeling neurons. In current narrative review, we will summarize role both pathophysiology therapeutic interventions neurodevelopmental adult mental with focus on autism spectrum disorders, drugs under preclinical clinical development treatment different that dysfunctions. Although evidence still limited more studies required, regulation attracting attention potential crucial target control diseases.

Language: Английский

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The neurobiology of stress: Vulnerability, resilience, and major depression

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(49)

Published: Nov. 27, 2023

The global agri-food system is simultaneously a major contributor to, and severely affected by, climate change. Agroecological farming systems can contribute to creating resilient systems. Based on multiyear qualitative case study, ...Supporting transitions sustainable, important ensure stable food supply in the face of growing extremes. Agroecology, or diversified based ecological principles, such ...

Language: Английский

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Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(6), P. 558 - 558

Published: May 30, 2024

Mood disorders and substance use disorder (SUD) are of immense medical social concern. Although significant progress on neuronal involvement in mood reward circuitries has been achieved, it is only relatively recently that the role glia these attracted attention. Detailed understanding glial functions devastating diseases could offer novel interventions. Here, following a brief review involved regulation perception, specific contributions neurotrophic factors, neuroinflammation, gut microbiota to highlighted. In this context, cells (e.g., microglia, astroglia, oligodendrocytes, synantocytes) phenotypic manifestation or SUD emphasized. addition, knowledge potential development therapeutics touched upon.

Language: Английский

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Gamma oscillations and excitation/inhibition imbalance: parallel effects of N-methyl D-aspartate receptor antagonism and psychosis

Biological Psychiatry Cognitive Neuroscience and Neuroimaging, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Auditory steady-state response (ASSR) abnormalities in the 40-Hz (gamma band) frequency have been observed schizophrenia and rodent studies of N-methyl D-aspartate glutamate receptor (NMDAR) hypofunction. However, extent to which ASSR resemble deficits induced by acute administration ketamine, an NMDAR antagonist, is not yet known. To address this knowledge gap, we conducted parallel EEG studies: a crossover, placebo-controlled ketamine drug challenge study healthy subjects (Study 1) comparison patients with controls 2). Time-frequency analysis was used calculate baseline, broadband gamma power, evoked total phase-locking factor, angle. Relative controls, exhibited increases pre-stimulus power reductions replicating prior studies. failed replicate previous findings phase delay schizophrenia. placebo, ketamine: increased reduced advanced ASSR. Normalized their respective control groups/conditions, direct these measures between data only revealed significant differences phase, supporting role hypofunction mediating oscillation

Language: Английский

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Esketamine at a Clinical Dose Attenuates Cerebral Ischemia/Reperfusion Injury by Inhibiting AKT Signaling Pathway to Facilitate Microglia M2 Polarization and Autophagy

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 369 - 387

Published: Jan. 1, 2025

This study aimed to assess the protective effect of a clinical dose esketamine on cerebral ischemia/reperfusion (I/R) injury and reveal potential mechanisms associated with microglial polarization autophagy. Experimental ischemia was induced by middle artery occlusion (MCAO) in adult rats simulated oxygen-glucose deprivation (OGD) BV-2 cells. Neurological sensorimotor function, infarct volume, histopathological changes, mitochondrial morphological apoptosis ischemic brain tissues were assessed presence or absence autophagy inducer rapamycin. The expression biomarkers related M1 M2 phenotypes determined immunofluorescence staining RT-qPCR, proteins AKT signaling pathway assayed Western blotting. Esketamine alone combined rapamycin alleviated neurological impairment, improved decreased mitigated tissue MCAO rats. Importantly, promoted phenotypic transition from both OGD-treated microglia, autophagy, inactivated signaling. Furthermore, effects enhanced addition at attenuates I/R inhibiting facilitate can provide an protection against injury. Thus, this provides new insights into neuroprotective therapeutic strategies

Language: Английский

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Rapid hippocampal synaptic potentiation induced by ketamine metabolite (2R,6R)-hydroxynorketamine persistently primes synaptic plasticity

Neuropsychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

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Repurposing General Anesthetic Drugs to Treat Depression: A New Frontier for Anesthesiologists in Neuropsychiatric Care

Anesthesiology, Journal Year: 2024, Volume and Issue: 141(2), P. 222 - 237

Published: June 10, 2024

During the last 100 years, role of anesthesiologists in psychiatry has focused primarily on facilitating electroconvulsive therapy and mitigating postoperative delirium other perioperative neurocognitive disorders. The discovery rapid sustained antidepressant properties ketamine, early results suggesting that general anesthetic drugs (including nitrous oxide, propofol, isoflurane) have properties, positioned at a new frontier treatment neuropsychiatric Moreover, shared interest understanding biologic underpinnings as psychotropic agents is eroding traditional academic boundaries between anesthesiology psychiatry. This article presents brief overview novel antidepressants identifies promising future candidates for depression. authors issue call to action outline strategies foster collaborations psychiatrists they work toward common goals repurposing addressing mood disorders surgical patients.

Language: Английский

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Low-Dose Sublingual Ketamine for the Treatment of Raynaud's Phenomenon

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Raynaud's phenomenon is a vascular disorder characterized by episodic vasospasm of small arteries, primarily affecting the hands and feet. Standard treatment strategies typically include lifestyle modifications to avoid cold exposure stress, alongside pharmacological interventions aimed at increasing blood flow reducing constriction. Ketamine, an FDA-approved anesthetic since 1970, exhibits analgesic vasodilatory properties that may enhance perfusion. This case report describes woman with primary whose symptoms improved significantly during low-dose sublingual ketamine prescribed for treatment-resistant depression. Further research into use this safe inexpensive medicine as recommended.

Language: Английский

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Decoding Neural Circuit Dysregulation in Bipolar Disorder: Toward an Advanced Paradigm for Multidimensional Cognitive, Emotional, and Psychomotor Treatment

Neuroscience & Biobehavioral Reviews, Journal Year: 2025, Volume and Issue: 169, P. 106030 - 106030

Published: Feb. 1, 2025

Bipolar disorder (BD) is characterized by a complex constellation of emotional, cognitive, and psychomotor disturbances, each deeply intertwined with underlying dysfunctions in large-scale brain networks neurotransmitter systems. This manuscript integrates recent advances neuroimaging, neuromodulation, pharmacological research to provide comprehensive view BD's pathophysiology, emphasizing the role network-specific their clinical manifestations. We explore how dysregulation within fronto-limbic network, particularly involving prefrontal cortex (PFC) amygdala, underpins emotional instability that defines both manic depressive episodes. Additionally, impairments central executive network (CEN) default mode (DMN) are linked cognitive deficits, hyperactivity DMN driving rumination inflexibility, while CEN underactivity contributes attentional lapses impaired function. Psychomotor symptoms, which oscillate between mania retardation depression, closely associated imbalances systems, dopamine serotonin, basal ganglia-thalamo-cortical motor pathway. Recent studies indicate these disturbances further exacerbated disruptions connectivity, leading control regulation. Emerging therapeutic strategies discussed, focus on neuromodulation techniques such as transcranial magnetic stimulation (TMS) deep (DBS), show promise restoring balance critical networks. Furthermore, interventions modulate synaptic functioning neuronal plasticity offer potential for addressing symptoms BD. underscores need an integrative treatment approach simultaneously targets neural circuits systems address full spectrum Drawing advancements neurobiological models frameworks, this proposal outlines pathway development precision-tailored interventions. These approaches designed optimize outcomes, ultimately striving elevate quality life individuals living bipolar (BD), remaining firmly grounded latest empirical evidence theoretical insights.

Language: Английский

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