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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Gut microbiota and intestinal immunity—A crosstalk in irritable bowel syndrome

Immunology, Journal Year: 2024, Volume and Issue: 172(1), P. 1 - 20

Published: Jan. 4, 2024

Irritable bowel syndrome (IBS), one of the most prevalent functional gastrointestinal disorders, is characterized by recurrent abdominal pain and abnormal defecation habits, resulting in a severe healthcare burden worldwide. The pathophysiological mechanisms IBS are multi-factorially involved, including food antigens, visceral hypersensitivity reactions, brain–gut axis. Numerous studies have found that gut microbiota intestinal mucosal immunity play an important role development crosstalk with multiple mechanisms. Therefore, based on existing evidence, this paper elaborates damage activation disturbance closely related to progression IBS. Combined application prospect, it also provides references for further in-depth exploration clinical practice.

Language: Английский

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Neuroinflammation through the vagus nerve-dependent gut–microbiota–brain axis in treatment-resistant depression

Progress in brain research, Journal Year: 2023, Volume and Issue: unknown, P. 61 - 77

Published: Jan. 1, 2023

Language: Английский

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Neuromodulatory control of complex adaptive dynamics in the brain

Interface Focus, Journal Year: 2023, Volume and Issue: 13(3)

Published: April 14, 2023

How is the massive dimensionality and complexity of microscopic constituents nervous system brought under sufficiently tight control so as to coordinate adaptive behaviour? A powerful means for striking this balance poise neurons close critical point a phase transition, at which small change in neuronal excitability can manifest nonlinear augmentation activity. brain could mediate transition key open question neuroscience. Here, I propose that different arms ascending arousal provide with diverse set heterogeneous parameters be used modulate receptivity target neurons-in other words, act mediating order. Through series worked examples, demonstrate how neuromodulatory interact inherent topological subsystems complex behaviour.

Language: Английский

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Aquatic Microbiomes Under Stress: The Role of Gut Microbiota in Detoxification and Adaptation to Environmental Exposures

Journal of Hazardous Materials Advances, Journal Year: 2025, Volume and Issue: unknown, P. 100612 - 100612

Published: Jan. 1, 2025

Language: Английский

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Role of the gut–brain axis via the subdiaphragmatic vagus nerve in stress resilience of 3,4-methylenedioxymethamphetamine in mice exposed to chronic restrain stress

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 189, P. 106348 - 106348

Published: Nov. 11, 2023

3,4-Methylenedioxymethamphetamine (MDMA) is the most widely used illicit substance worldwide. Nevertheless, recent observational studies demonstrated that lifetime MDMA use among U.S. adults was associated with a lower risk of depression and suicide thoughts. We recently reported gut-brain axis may contribute to MDMA-induced stress resilience in mice. To further explore this, we investigated effects subdiaphragmatic vagotomy (SDV) modulating mice subjected chronic restrain (CRS). Pretreatment (10 mg/kg/day for 14 days) blocked anhedonia-like behavior reduced expression synaptic proteins brain-derived neurotrophic factor prefrontal cortex (PFC) CRS-exposed Interestingly, SDV beneficial on these alterations Analysis gut microbiome revealed four measures α-diversity between sham + CRS group group. Moreover, specific microbes differed vehicle group, differences microbial composition were observed all groups. Untargeted metabolomics analysis showed prevented increase plasma levels three compounds [lactic acid, 1-(2-hydroxyethyl)-2,2,6-tetramethyl-4-piperidinol, 8-acetyl-7-hydroxyvumaline] positive correlations found two abundance several across In conclusion, our data suggest via vagus nerve might MDMA.

Language: Английский

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Therapeutic modulation of the kynurenine pathway in severe mental illness and comorbidities: A potential role for serotonergic psychedelics

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2024, Volume and Issue: 134, P. 111058 - 111058

Published: June 15, 2024

Mounting evidence points towards a crucial role of the kynurenine pathway (KP) in altered gut-brain axis (GBA) balance severe mental illness (SMI, namely depression, bipolar disorder, and schizophrenia) cardiometabolic comorbidities. Preliminary shows that serotonergic psychedelics their analogues may hold therapeutic potential addressing KP dysregulated GBA SMI In fact, aside from effects on mood, elicit improvement preclinical models obesity, metabolic syndrome, vascular inflammation, which are highly comorbid with SMI. Here, we review literature modulation comorbidities, application to address brain systemic dysfunction underlying Psychedelics might therapeutically modulate comorbidities either directly, via altering by influencing rate-limiting enzymes affecting levels available tryptophan, or indirectly, gut microbiome, metabolome, metabolism, immune system. Despite promising preliminary evidence, mechanisms outcomes remain largely unknown require further investigation. Several concerns discussed surrounding side this approach specific cohorts individuals

Language: Английский

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A role for the serotonin 2A receptor in the expansion and functioning of human transmodal cortex

Brain, Journal Year: 2023, Volume and Issue: 147(1), P. 56 - 80

Published: Sept. 11, 2023

Integrating independent but converging lines of research on brain function and neurodevelopment across scales, this article proposes that serotonin 2A receptor (5-HT2AR) signalling is an evolutionary developmental driver potent modulator the macroscale functional organization human cerebral cortex. A wealth evidence indicates anatomical cortex follows a unimodal-to-transmodal gradient. Situated at apex processing hierarchy-where it plays central role in integrative processes underpinning complex, human-defining cognition-the transmodal has disproportionately expanded development evolution. Notably, adult especially rich 5-HT2AR expression recent suggests that, during early development, neural progenitor cells stimulates their proliferation-a critical process for evolutionarily-relevant cortical expansion. Drawing multimodal neuroimaging cross-species investigations, we argue by contributing to expansion being prevalent its hierarchy brain, major both functioning. Owing unique excitatory downstream cellular effects, neuronal agonism promotes neuroplasticity, learning cognitive psychological flexibility context-(hyper)sensitive manner with therapeutic potential. Overall, delineate dual 5-HT2ARs enabling modulation

Language: Английский

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Modulating arousal to overcome gait impairments in Parkinson’s disease: how the noradrenergic system may act as a double-edged sword

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: March 26, 2023

Abstract In stressful or anxiety-provoking situations, most people with Parkinson’s disease (PD) experience a general worsening of motor symptoms, including their gait impairments. However, proportion patients actually report benefits from experiencing—or even purposely inducing—stressful high-arousal situations. Using data large-scale international survey study among 4324 PD and impairments within the online Fox Insight (USA) ParkinsonNEXT (NL) cohorts, we demonstrate that individuals deploy an array mental state alteration strategies to cope impairment. Crucially, these differ along axis arousal—some act heighten, whereas others diminish, overall sympathetic tone. Together, our observations suggest arousal may as double-edged sword for control in PD. We propose theoretical, neurobiological framework explain why heightened can have detrimental effects on occurrence severity some individuals, while alleviating them others. Specifically, postulate this seemingly contradictory phenomenon is explained by inherent features ascending system: namely, related task performance inverted u-shaped curve (the so-called Yerkes Dodson relationship). noradrenergic locus coeruleus plays important role modulating symptom expression, regulating mediating network-level functional integration across brain. The ability facilitate dynamic ‘cross-talk’ between distinct, otherwise largely segregated brain regions necessary cerebral compensation presence suboptimal arousal, compensatory networks be too allow adequate compensation. Conversely, supraoptimal increased cross-talk competing inputs complementary emerge become dysfunctional. Because degenerates progression, finetuning delicate balance becomes increasingly difficult, heightening need self-modulate shifting sub- improve performance. Recognition underlying mechanism emphasises importance PD-specific rehabilitation alleviate disability.

Language: Английский

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Repeated use of 3,4-methylenedioxymethamphetamine is associated with the resilience in mice after chronic social defeat stress: A role of gut–microbiota–brain axis

Psychiatry Research, Journal Year: 2022, Volume and Issue: 320, P. 115020 - 115020

Published: Dec. 21, 2022

3,4-Methylenedioxymethamphetamine (MDMA), the most widely used illicit compound worldwide, is attractive therapeutic drug for post-traumatic stress disorder (PTSD). Recent observational studies of US adults demonstrated that lifetime MDMA use was associated with lower risk depression. Here, we examined whether repeated administration can affect resilience versus susceptibility in mice exposed to chronic social defeat (CSDS). CSDS produced splenomegaly, anhedonia-like phenotype, and higher plasma levels interleukin-6 (IL-6) saline-treated mice. In contrast, did not cause these changes MDMA-treated Analysis gut microbiome found several microbes altered between saline + group group. Untargeted metabolomics analysis showed N-epsilon-methyl-L-lysine were significantly than those control groups. Interestingly, there positive correlations IL-6 abundance (or N-epsilon-methyl-L-lysine) three Furthermore, also conclusion, data suggest might contribute subjected through gut–microbiota–brain axis.

Language: Английский

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