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

European Archives of Psychiatry and Clinical Neuroscience, Год журнала: 2024, Номер unknown

Опубликована: Фев. 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

Язык: Английский

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The role of serotonin in depression—A historical roundup and future directions

Journal of Neurochemistry, Год журнала: 2024, Номер unknown

Опубликована: Март 13, 2024

Abstract Depression is one of the most common psychiatric disorders worldwide, affecting approximately 280 million people, with probably much higher unrecorded cases. associated symptoms such as anhedonia, feelings hopelessness, sleep disturbances, and even suicidal thoughts. Tragically, more than 700 000 people commit suicide each year. Although depression has been studied for many decades, exact mechanisms that lead to are still unknown, available treatments only help a fraction patients. In late 1960s, serotonin hypothesis was published, suggesting key player in depressive disorders. However, this being increasingly doubted there evidence influence other neurotransmitters, noradrenaline, glutamate, dopamine, well larger systemic causes altered activity limbic network or inflammatory processes. narrative review, we aim contribute ongoing debate on involvement depression. We will review evolution antidepressant treatments, research over years, future applications bridge gap between neurotransmitter dynamics using biosensors. These new tools combination applications, provide deeper understanding serotonergic

Язык: Английский

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1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents – A Review

ACS Pharmacology & Translational Science, Год журнала: 2024, Номер 7(6), С. 1722 - 1745

Опубликована: Май 8, 2024

1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI, or DOX where X = −I) was first synthesized in 1973 a structure–activity study to explore the effect of various aryl substituents on then newly identified, and subsequently controlled, hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM, −CH3). Over time, DOI found be serotonin (5-HT) receptor agonist using peripheral 5-HT tissue assays later, following identification multiple families central receptors, an at 5-HT2 receptors rat and, then, human brain. Today, classical hallucinogens, currently referred as serotonergic psychedelic agents, are receiving considerable attention for their potential therapeutic application neuropsychiatric disorders including treatment-resistant depression. Here, we review, historical current developments that led becoming unique, perhaps landmark, research.

Язык: Английский

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Psychedelic control of neuroimmune interactions governing fear

Nature, Год журнала: 2025, Номер unknown

Опубликована: Апрель 23, 2025

Язык: Английский

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Impact of psilocybin on cognitive function: A systematic review

Psychiatry and Clinical Neurosciences, Год журнала: 2024, Номер 78(12), С. 744 - 764

Опубликована: Окт. 1, 2024

Psilocybin is a classic psychedelic with demonstrated preliminary clinical efficacy in range of psychiatric disorders. Evaluating the impact psilocybin on cognitive function essential to unravel its potential benefits and risks. In this systematic review, we assessed psilocybin's effect through comprehensive search electronic databases from inception January 2024, identifying 20 articles involving 2,959 participants. While 85% studies were conducted healthy volunteers, most these (85%) used macrodoses, ranging 45 μg/kg 30 mg/70 kg. Various aspects evaluated yielded mixed results. Global function, processing speed remained mostly unchanged individuals; However, limited number reported improvements certain areas such as sustained attention, working memory, executive especially patients treatment‐resistant depression (TRD). Emotional was positively modified, particularly TRD patients. observed enhance emotional empathy without significantly altering social cognition. Cognitive flexibility creative cognition noted initially decline but could potentially improve over time. Additionally, respect learning memory skills, showed promise improving specific types semantic associations associative learning, while effects episodic verbal have been less pronounced compared other enhancers. The findings underscore complexity influence. Further research provide clearer understanding domains guide development safe effective interventions.

Язык: Английский

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Mucuna pruriens to treat Parkinson's disease in low-income countries: Recommendations and practical guidelines from the farmer to clinical trials. Paving the way for future use in clinical practice

Parkinsonism & Related Disorders, Год журнала: 2024, Номер 124, С. 106983 - 106983

Опубликована: Май 8, 2024

Язык: Английский

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Serotonergic neuromodulation of synaptic plasticity

Neuropharmacology, Год журнала: 2024, Номер 257, С. 110036 - 110036

Опубликована: Июнь 12, 2024

Язык: Английский

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Early psilocybin intervention alleviates behavioral despair and cognitive impairment in stressed Wistar rats

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Год журнала: 2025, Номер unknown, С. 111243 - 111243

Опубликована: Янв. 1, 2025

Chronic stress exerts profound effects on mental health, contributing to disorders such as depression, anxiety, and cognitive impairment. This study examines the potential of psilocybin alleviate behavioral despair deficits in a rodent model chronic stress, focusing interplay between Hypothalamic-Pituitary-Adrenal (HPA) axis Endocannabinoid System (ECS). Twenty-two male Wistar rats were divided into control groups. Animals within group exposed predator odor social instability induce either sham treated, or given psilocybin. Behavioral assessments conducted using Open Field Test, Sucrose Preference Novel Object Recognition, Elevated Plus Maze, Forced Swimming Test evaluate locomotion, anhedonia, memory, despair, respectively. Blood brain samples analyzed for biochemical markers. Results indicated that significantly reduced stress-induced impairments, likely through ECS-mediated downregulation HPA axis. These findings suggest early intervention with has sustained beneficial stress-related disturbances, underscoring its novel therapeutic approach health disorders.

Язык: Английский

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The Chronobiological and Neuroprotective Mechanisms of Resveratrol in Improving Sleep

Mediators of Inflammation, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

According to statistics, more than one‐third of the global population currently experiences sleep problems, and about 10% adults have been diagnosed with insomnia, a proportion that is increasing annually. Most used insomnia medications are not specifically developed but discovered by chance, often resulting in unavoidable side effects like addiction. Thus, there an urgent need find safer effective therapeutic options. Resveratrol, natural polyphenolic compound, shows significant potential improving insomnia. Research its may be achieved through multiple biological processes, including antiapoptosis, antioxidant activity, anti‐inflammation, circadian rhythm regulation, modulation neurotransmitters (gamma‐aminobutyric acid (GABA), DA, 5‐HT, cortisol), increased levels neurotrophic factor BDNF. Additionally, resveratrol’s treatment closely linked SIRT1, AMPK, NF‐ κ B, mTOR, PI3K/Akt, MAPK pathways. This review summarizes mechanisms resveratrol treating provide researchers deeper understanding action, which can aid development novel targeted drugs offer innovative ideas methods for clinical treatment.

Язык: Английский

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Toluene Toxicity in the Brain: From Cellular Targets to Molecular Mechanisms

The Annual Review of Pharmacology and Toxicology, Год журнала: 2025, Номер 65(1), С. 487 - 506

Опубликована: Янв. 23, 2025

Toluene intoxication constitutes a persistent public health problem worldwide. While most organs can be damaged, the brain is primary target whether exposure accidental, occupational, or recreational. Interventions to prevent/revert damage by toluene are curtailed scarce information on molecular targets and mechanisms mediating toluene's toxicity common other neurotoxins and/or coexistence of neurological/psychiatric disorders. We examine (a) physicochemical properties that allow this inhalant primarily lipid-rich brain; (b) cell types targeted (neurons, different glia), while considering cerebrovascular component; (c) putative which may modify receptor function analyzing structural features directly interact with membrane lipids specific proteins. This stepping stone design pharmacotherapies counteract intoxication.

Язык: Английский

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