International Journal of Molecular Sciences

Multilevel Mechanisms and Clinical Efficacy of Psilocybin in Depression Treatment: A Systematic Review

International Journal of Molecular Sciences September 10, 2026 Xizhen Zhang, Xiaowen Zhang, Haiyu Zhang et al.

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...

DOI: 10.3390/ijms27188052

Neuronal Microtubules and Radiofrequency Waves: The Quantum Core of Human Consciousness, Memory, and Pathway to Memory Enhancement/Recovery.

International Journal of Molecular Sciences July 7, 2026 Gary W Arendash

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...

DOI: 10.3390/ijms27136090 Full text Alzheimer’s disease Environmentally-induced decoherence Biophotons Consciousness +5

Skin on Drugs: Psychotropic Compounds in Cutaneous Biology

International Journal of Molecular Sciences June 26, 2026 M. Fernández‐guarino, Nicolás Yagüe-septién, Laura Marín-ochoa et al.

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...

DOI: 10.3390/ijms27135808 Serotonergic Psilocybin Serotonin Fluoxetine +9

Psilocybin in Older Adults: Therapeutic Opportunities in Inflammation-Driven Disorders of Aging-From Depression to Neurodegeneration.

International Journal of Molecular Sciences May 9, 2026 Marta Jóźwiak-Bębenista, Anna Stasiak, Monika Sienkiewicz et al.

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...

DOI: 10.3390/ijms27104229 Full text Depression Psilocybin Serotonin 5-ht2a +5

The Use of Psychedelics in the Treatment of Adult ADHD: A Systematic and Mechanistic Review.

International Journal of Molecular Sciences April 12, 2026 James Chmiel, Agnieszka Malinowska, Donata Kurpas

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...

DOI: 10.3390/ijms27083453 Full text ADHD Neurodevelopmental disorders Pharmacotherapy Psychedelics

The Ethnopharmacological Use of Mescaline for Psychiatric Disorders: A Systematic Review

International Journal of Molecular Sciences March 28, 2026 Jonathan Shaw, Aidan Yong, Jacky Lee et al.

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...

DOI: 10.3390/ijms27073081 Mescaline Alternative medicine Depression economics Systematic review +4

Beyond the Genomic Storm: Evaluating Tabernanthalog as a Potential Scaffold for Silent Neuroplasticity and Broad-Spectrum Therapy

International Journal of Molecular Sciences March 20, 2026 Ivan Anchesi, Ivana Raffaele, M. Astorino et al.

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...

DOI: 10.3390/ijms27062811 Neuroplasticity Synaptic plasticity Cognition Schizophrenia object-oriented programming +7

Kappa-Opioid Receptor Antagonism Prolongs the Antidepressant Effects of Ketamine in Adult Mice with Depression-like Behavior Induced by Adolescent Chronic Unpredictable Stress

International Journal of Molecular Sciences March 20, 2026 Ana Zivanovic, Milos Mitic, Iva Lukic et al.

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...

DOI: 10.3390/ijms27062815

Predictors of the Effectiveness of Psychedelics in Treating Depression—A Scoping Review

International Journal of Molecular Sciences February 26, 2026 James Chmiel, Filip Rybakowski

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...

DOI: 10.3390/ijms27052202 Comorbidity Antidepressant Psycinfo Medline +5

State-Dependent Remodeling of Astrocytic Proteome and Phosphorylation Signaling Networks Across Wake, Sleep, and General Anesthesia.

International Journal of Molecular Sciences February 25, 2026 Mengchan Su, Qingran Li, Ping Liao et al.

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...

DOI: 10.3390/ijms27052159 Full text Astrocyte Consciousness General anesthesia Phosphoproteomics +1

Molecular Mechanisms of Emerging Antidepressant Strategies: From Ketamine to Neuromodulation

International Journal of Molecular Sciences December 28, 2025 Mateusz Kowalczyk, David Aebisher, Jakub Szpara et al. 3 citations

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,...

DOI: 10.3390/ijms27010344 Major depressive disorder Treatment-resistant depression Neuromodulation Monoaminergic +10

Altered Network Function in Hippocampus After Sub-Chronic Activation of Cannabinoid Receptors in Early Adolescence.

International Journal of Molecular Sciences December 18, 2025 Johanna Rehn, Lucas Admeus, Bernat Kocsis

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...

DOI: 10.3390/ijms262412182 Full text Cannabis 1 receptor Early adolescent vulnerability Hippocampal theta rhythm Oscillatory neural networks

3-CMC: Acute Effects in Male and Female Mice, Human Intoxication Case Series (Italy, 2014–2025), and Prediction of ADMET Properties

International Journal of Molecular Sciences November 29, 2025 Marta Bassi, Elisa Roda, Giorgia Corli et al.

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...

DOI: 10.3390/ijms262311600 Cardiotoxicity Prepulse inhibition Psychomotor learning Acute toxicity +4

Microdosing Psychedelics to Restore Synaptic Density in Schizophrenia.

International Journal of Molecular Sciences September 14, 2025 Jacopo Sapienza, Marco Spangaro, Stefano Comai et al. 2 citations

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...

DOI: 10.3390/ijms26188949 Full text Neuroplasticity Psilocybin Microdosing Sv2a +9

Substance Abuse and Cognitive Decline: The Critical Role of Tau Protein as a Potential Biomarker

International Journal of Molecular Sciences August 7, 2025 Liliana Rebolledo-Pérez, Jorge Hernández‐bello, Alicia Martínez-ramos et al. 5 citations

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...

DOI: 10.3390/ijms26157638 Biomarker Cognition Cognitive decline

Tabernanthalog, a Non-Hallucinogenic Psychedelic, Alleviates Cancer-Induced Cognitive Deficits via Serotonergic Pathways

International Journal of Molecular Sciences August 4, 2025 Masahide Arinaga, Jun Yamada, Shoichiro Maeda et al. 2 citations

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...

DOI: 10.3390/ijms26157519 Serotonergic Serotonin Neuroinflammation Hippocampal formation +2

The Effect of Ketamine on the Immune System in Patients with Treatment-Resistant Depression

International Journal of Molecular Sciences August 1, 2025 Łukasz P. Szałach, Klaudia Ciesielska-Figlon, A. Daca et al. 7 citations

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...

DOI: 10.3390/ijms26157500

Molecular Pathways Potentially Involved in Hallucinatory Experiences During Sleep Paralysis: The Emerging Role of β-Arrestin-2

International Journal of Molecular Sciences July 26, 2025 Lena M. Rudy, Michał M. Godlewski 2 citations

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...

DOI: 10.3390/ijms26157233 Serotonergic Serotonin Sleep paralysis Sensory system +3

The Effects of Psychotherapy on Single and Repeated Ketamine Infusion(s) Therapy for Treatment-Resistant Depression: The Convergence of Molecular and Psychological Treatment.

International Journal of Molecular Sciences July 11, 2025 Sofia Sakopoulos, Mcwelling Todman 6 citations

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...

DOI: 10.3390/ijms26146673 Full text Ketamine infusion therapy Ketamine-assisted psychotherapy kap Rapid-acting antidepressant Treatment-resistant depression trd +2

The Astroglia Syncytial Theory of Consciousness.

International Journal of Molecular Sciences June 17, 2025 James M Robertson 3 citations

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...

DOI: 10.3390/ijms26125785 Full text Astrocytes and consciousness Glia-neuronal interactions Theory of consciousness Unified brain function +5

Mitochondrial Calcium Uniporter (MCU)-Mediated Calcium Overload in Psychoactive Drug Neurotoxicity: From Pathogenesis to Therapeutic Targets.

International Journal of Molecular Sciences May 15, 2025 Xinyan Yang, Yinyu Chen, Gaolin Zheng et al. 3 citations

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...

DOI: 10.3390/ijms26104732 Full text Calcium overload Neurotoxicity Psychoactive substances Calcium signaling +3

The Behavioral and Neuroinflammatory Impact of Ketamine in a Murine Model of Depression and Liver Damage.

International Journal of Molecular Sciences April 10, 2025 Mădălina Iuliana Mușat, Ana-Maria Ifrim-Predoi, Smaranda Ioana Mitran et al. 5 citations

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...

DOI: 10.3390/ijms26083558 Full text Cums Mcd diet Nafld Depression-treatment +4

Epigenetic Echoes: Bridging Nature, Nurture, and Healing Across Generations.

International Journal of Molecular Sciences March 27, 2025 Blerida Banushi, Jemma Collova, Helen Milroy 19 citations

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...

DOI: 10.3390/ijms26073075 Full text Neuroplasticity Dna methylation Epigenetics Histones +7

Acute Effects of the Psychedelic Phenethylamine 25I-NBOMe in C57BL/6J Male Mice.

International Journal of Molecular Sciences March 20, 2025 Sabrine Bilel, Cristina Miliano, Giorgia Corli et al. 3 citations

25I-NBOMe (4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl) phenethylamine) is a synthetic psychedelic compound abused for its ambiguous legal state as a counterfeit lysergic acid diethylamide (LSD). 25I-NBOMe acts as a selective agonist of 5HT2A receptors leading to hallucinations, intoxications, and fatalities. Here, we assessed the rewarding properties of 25I-NBOMe and its behavioral and neurotoxic...

DOI: 10.3390/ijms26062815 Full text Synaptic plasticity 25i-nbome 5ht2a agonist Ltd +8

Beyond NMDA Receptors: A Narrative Review of Ketamine's Rapid and Multifaceted Mechanisms in Depression Treatment.

International Journal of Molecular Sciences December 20, 2024 Zuzanna Antos, Xawery Żukow, Laura Bursztynowicz et al. 14 citations

The rising prevalence of depression, with its associated suicide risk, demands effective fast-acting treatments. Ketamine has emerged as promising, demonstrating rapid antidepressant effects. While early studies show swift mood improvements, its precise mechanisms remain unclear. This article aims to compile and synthesize the literature on ketamine's molecular actions. Ketamine primarily works...

DOI: 10.3390/ijms252413658 Full text Ketamine Neuroplasticity Bdnf Nmda antagonist +7

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