Nonhallucinogenic psychoplastogens, such as tabernanthalog (TBG), are being developed as potentially safer, more scalable alternatives to psychedelics for promoting neuronal growth and treating various brain conditions. Currently, it is unclear whether 5-hydroxytryptamine 2A (5-HT2A) receptors and immediate early gene (IEG) activation have a role in the neuroplasticity-promoting effects of...
The resurgence of interest in psychedelic compounds as potential treatments for psychiatric disorders represents a paradigm shift in mental health care. Psychedelics exert their effects through serotonergic modulation, particularly via 5-HT2A receptor activation, inducing profound alterations in consciousness and catalyzing neuroplasticity. While their neurobiological effects are...
Serotonergic psychedelics, including the recreationally used psilocybin and LSD, have become promising therapeutic agents for the treatment of treatment-resistant depression. While it is generally agreed that they exhibit their antidepressant effects by inducing rapid and sustained neuroplasticity, the molecular mechanisms responsible are widely debated. In particular, the role of the serotonin...
Abstract Background The full therapeutic potential of serotonergic psychedelics (SP) in treating neuropsychiatric disorders, such as depression and schizophrenia, is limited by possible adverse effects, including perceptual disturbances and psychosis, which require administration in controlled clinical environments. This study investigates the potential synergistic benefits of combining...
Major depressive disorder (MDD) remains a significant global health burden, and its current treatments are limited by the delayed onset of efficacy weeks after dosing. While esketamine and psychedelics were clinically successful as rapid-acting antidepressants in recent years, these molecules are heavily associated with psychotic side effects and the risks of substance abuse. In this study, we...
This research focuses on the promising use of esketamine in perinatal depression, a widespread disorder impacting postpartum women's mental health. Despite esketamine's known rapid antidepressant effects, its precise mechanisms are not fully understood. This study integrates clinical and preclinical approaches to explore esketamine's efficacy in treating perinatal depression and its actions...
bioRxiv Preprint ServerJuly 23, 2025Tomas Del Olmo, Mathilde Decourcelle, Martial Séveno et al.
preprint
The serotonin (5-HT)2A receptor is the primary target of numerous psychoactive drugs including serotonergic psychedelics, and mediates psychedelics-induced neuroplasticity, but the signaling mechanisms involved remain poorly characterized. Using quantitative phosphoproteomics, we show that the administration of the hallucinogenic 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) to...
Introduction: Psychedelics are emerging as potential treatments for neuropsychiatric conditions, with evidence suggesting a single administration can lead to enduring behavioural changes. While the underlying putative mechanism(s) remain unclear, there is evidence supporting altered learning as a key candidate. Aim: This systematic review examined studies assessing the effects of psychedelics...
Traumatic brain injury (TBI) is a significant global health challenge, with limited effective treatments for its acute and chronic consequences. TBI is characterized by neuroinflammation, oxidative stress, impaired neuroplasticity, imbalances in neurotransmission, and cell death - factors that contribute to the development of neurological and psychiatric disorders. Emerging evidence suggests...
Neuropsychiatric disorders reflect disruptions in brain network dynamics along an "order-complexity-chaos" continuum. Psychedelics may therapeutically increase neural entropy, disrupt maladaptive patterns, and promote network reorganization. This system-level framework emphasizes dynamic connectome remodeling over static molecular correction, offering a novel strategy for treating psychiatric...
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...
Arketamine, the (R)-enantiomer of (R,S)-ketamine, shows even greater rapid and sustained antidepressant-like effects in rodent models compared to esketamine, yet the underlying mechanisms remain unclear. In this study, we used the chronic social defeat stress (CSDS) model to investigate how arketamine exerts its antidepressant-like effects. We found that activating cAMP response element-binding...
Molecular PsychiatryJuly 7, 2025Dongsun Park, Gwangho Lee, Won-Gyu Lee et al.7 citations
Major depressive disorder is a debilitating condition, with many patients unresponsive to conventional monoaminergic antidepressants. Rapid-acting antidepressants such as ketamine and psilocybin offer promising alternatives, relieving symptoms within hours. Ketamine, an NMDA receptor antagonist, and psilocybin, a serotonergic psychedelic primarily targeting 5-HT2A receptors, both enhance...
The objective of the present study was to characterize the effects of long-term meditation (LTM) on directed connectivity patterns during resting-state and meditative brain states. Specifically, it was aimed to identify major cortical sources of information flow and target regions of information influx, and to reveal which frequency-specific oscillatory networks are critically involved in...
Psychedelic compounds such as ketamine and MDMA have shown therapeutic promise for mood and trauma-related disorders, yet their molecular mechanisms remain unclear. This study applied a Brain-Epigenome-Wide Association Study (BEWAS) to assess DNA methylation changes in brain-enriched genes following treatment. Pre- and post-treatment blood (ketamine, N = 20) and saliva (MDMA, N = 16) samples...
The resurgence of interest in classical psychedelics brings both promise and challenges to psychiatric care. Increasing evidence supports the therapeutic potential of psychedelics for a range of mental health conditions, and approval for clinical use appears inevitable. The psychedelic-associated acute subjective experience may mediate or enhance therapeutic outcomes, but also presents...
The subject of the study is phenomenological neuroplasticity, considered as a key biological mechanism that ensures the emergence and development of consciousness. The object of the research is the process of forming subjective phenomenal experience, realized through the dynamic restructuring of neural networks in the brain. Special attention is given to the evolutionary role of...
Mindfulness-based interventions (MBIs) have shown promise in reducing stress among family caregivers (FCs) of people with dementia (PWD). However, the long-term stress-relieving effects of traditional MBIs are often limited by challenges in maintaining regular practice, leading to issues with adherence and attrition. To address these limitations, this study protocol aims to test a novel...
Schizophrenia is a highly disabling psychopathology that is a significant burden on public health systems and is characterized by both positive and negative symptoms. One of these negative symptoms is social isolation, which responds poorly to available treatments. Ketamine (KET) has been shown to enhance social behavior in various preclinical models, accompanied by neurobiological changes. In...
Psilocybin, a serotonergic psychedelic, has demonstrated therapeutic potential in neuropsychiatric disorders. While its neuroplastic and immunomodulatory effects are recognized, the underlying mechanisms remain unclear. This study investigates how psilocybin and its active metabolite, psilocin, influence microglial inflammatory responses and neurotrophic factor expression through serotonergic...