Depression, characterized by persistent low mood and anhedonia, represents a prevalent affective disorder imposing substantial medical and economic burdens. Current first-line antidepressants are limited by delayed onset and treatment resistance. Psilocybin (PSI) has re-emerged as a promising therapeutic agent with rapid, sustained antidepressant effects. This systematic review was conducted...
A unifying theory of both human consciousness and memory is presented that is based on neuronal microtubules (MTs) being central to both, and different populations of pyramidal cells in neocortex and hippocampus being responsible for consciousness or memory. First, two quantum theories of consciousness are presented-the Orchestrated Objective Reduction (Orch OR) theory of Penrose/Hameroff and...
Recent evidence reveals that several psychotropic compounds exert significant biological effects on the skin through neurochemical and immunomodulatory pathways. Cannabinoids such as tetrahydrocannabinol (THC) show potent anti-inflammatory, antipruritic, and anti-aging properties when applied topically, and may hold therapeutic potential. Antidepressants, particularly fluoxetine (Prozac), have...
Aging is associated with chronic, low-grade inflammation ("inflammaging"), which contributes to neuropsychiatric and neurodegenerative disorders such as depression, Alzheimer's disease, and Parkinson's disease. Conventional pharmacotherapies often provide limited benefit in older adults and are further complicated by polypharmacy and drug-drug interactions. Psilocybin, a serotonergic...
Interest in classical psychedelics as potential treatments for ADHD has grown alongside broader psychiatric psychedelic research, but ADHD-specific evidence remains limited. This systematic review examined prospective and experimental studies on whether classical psychedelics, including microdosing-like use and retreat-based exposure, are associated with changes in adult ADHD symptoms and...
Mescaline, the primary bioactive alkaloid found in Peyote and San Pedro cactus, has been used in traditional medicine for centuries and is now attracting renewed interest for clinical applications. The purpose of this systematic review was to search the literature for studies reporting the use of mescaline to address the gap in our understanding of mescaline use and its impact. References were...
The clinical renaissance of psychedelic medicine has highlighted the therapeutic potential of rapid-acting neuroplastogens, or "psychoplastogens," for psychiatric disorders. However, the widespread application of classical psychedelics-such as psilocybin and LSD-and the atypical dissociative ibogaine is severely limited by their hallucinogenic properties and, particularly in the case of...
Major depressive disorder (MDD) is a highly prevalent psychiatric illness for which rapid-acting antidepressants such as ketamine provide only transient benefit. Because κ-opioid receptor (KOR) signaling contributes to stress-related dysphoria and impaired neuroplasticity, we examined whether KOR antagonism could prolong ketamine’s antidepressant-like effects in a mouse model of adolescent...
Psychedelic-assisted therapies (PATs) can produce rapid and sustained antidepressant effects, yet variability in response remains substantial. Identifying predictors and moderators is essential for optimising patient selection, preparation, and delivery. To map and synthesise the evidence on the predictors of antidepressant response to classic/serotonergic psychedelics administered with...
Astrocytes critically regulate states of consciousness, yet their molecular profiles across wake, sleep, and general anesthesia remain unclear. This study conducted proteomic and phosphoproteomic analyses of rat cortical astrocytes across these states using sevoflurane. Data quality was validated using principal component analysis (PCA) and Pearson correlation coefficient (PCC). Proteomics...
Depression is a common, debilitating, and potentially life-threatening mental disorder affecting individuals across all age groups and populations. It represents one of the major challenges of contemporary medicine. It is estimated that more than 300 million people worldwide are affected, and patients with major depressive disorder (MDD) exhibit a significantly increased risk of suicide,...
The cannabinoid 1-receptor (CB1R) is found in particularly high levels in the hippocampus (HPC). Increased CB1R density and binding are observed in patients with schizophrenia, and epidemiological studies suggest that regular cannabis use during adolescence is a risk factor for the disease. CB1R was shown to interfere with neuronal network oscillations and to impair sensory gating and memory...
3-chloromethcathinone (3-CMC) is a synthetic cathinone that gained relevance, having been involved in a large number of seizures and poisoning reports. Despite this, literature currently lacks information on its pharmaco-toxicological effects. This study aims to investigate the acute sensorimotor and physiological effects of 3-CMC (0.1-30 mg/kg; i.p.) in male and female CD-1 mice and its...
Schizophrenia is a highly polygenic disease, and several genetic variants associated with the disease converge on altered synaptic homeostasis. In particular, the gene encoding complement component 4 (C4) showed the strongest association with schizophrenia, and this protein is involved in complement-dependent and microglia-mediated synaptic pruning. As a matter of fact, microglia are overactive...
Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). Emerging evidence suggests...
Cancer-related cognitive impairment (CRCI)-encompassing anxiety, depression, and memory deficits-significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a novel intervention for CRCI using a...
Treatment-resistant depression (TRD) is associated with immune dysregulation. Ketamine, a rapid-acting antidepressant, may exert effects via immunomodulation. The aim was to examine ketamine’s impact on immune markers in TRD, including T-cell subsets, cytokines, and in vitro T-cell responses. Eighteen TRD inpatients received 0.5 mg/kg iv ketamine. Blood was sampled at baseline, 4 h, and 24 h to...
Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impressions include personification of an...
Ketamine infusion therapy has gained recognition as an innovative treatment for treatment-resistant depression (TRD), demonstrating rapid and robust antidepressant effects. Its therapeutic promise is increasingly understood to involve molecular and neurobiological processes that promote neural plasticity and cognitive flexibility. These changes may create a unique window for psychotherapeutic...
The neurological basis of consciousness remains unknown despite innumerable theories proposed for over a century. The major obstacle is that empirical studies demonstrate that all sensory information is subdivided and parcellated as it is processed within the brain. A central region where such diverse information combines to form conscious expression has not been identified. A novel hypothesis...
Salvia divinorum is a psychoactive plant presenting a complex pharmacological profile, attracting significant scientific interest due to its potential therapeutic applications and associated health risks. This review provides a comprehensive analysis of the toxic and therapeutic effects of S. divinorum, evaluating its potential medical applications while highlighting the risks associated with...
With rapid societal changes and increasing stress levels, the abuse of psychoactive substances has emerged as a global health crisis. Studies indicate that the mitochondrial calcium uniporter (MCU) plays a pivotal role in neurotoxic damage induced by psychoactive substances. As the primary channel for mitochondrial Ca2+ uptake, MCU dysfunction can lead to Ca2+ overload, oxidative stress, and...
Non-alcoholic fatty liver disease (NAFLD) has been associated with depression and inadequate response to antidepressants. While ketamine has demonstrated efficacy in treating depression, its impact on pre-existing liver injury and depression remains unclear. This study aimed to evaluate the effects of ketamine treatment in a murine model of depression and liver damage, considering age-related...
Trauma can impact individuals within a generation (intragenerational) and future generations (transgenerational) through a complex interplay of biological and environmental factors. This review explores the epigenetic mechanisms that have been correlated with the effects of trauma across generations, including DNA methylation, histone modifications, and non-coding RNAs. These mechanisms can...