MDMA's history spans military experimentation, recreational use, and clinical trials for PTSD treatment, reflecting both promise and controversy. While studies in heavy users suggested possible neurotoxicity, evidence remains inconclusive. Clinical trials show that one to three sessions of MDMA-assisted psychotherapy can alleviate PTSD symptoms, yet regulators have criticized inadequate...
The discovery that a single subanesthetic dose of (R,S)-ketamine induces rapid and long-lasting antidepressant effects by a completely different mechanism represents one of the most substantial break-throughs in depression pharmacotherapy. The recent study in Nature by Yue and colleagues represents a signi fi cant conceptual and technical advance by identifying NMDA-independent transient...
Molecular PsychiatryApril 1, 2026Zijian Lv, Qifeng Xie, Kecan Li et al.3 citations
Chronic stress induces neurobiological adaptations that manifest as altered behavioral patterns in both humans and animal models. To enhance the translational value of preclinical research, we systematically evaluated chronic restraint stress (CRS) protocols in mice through longitudinal tracking of behavioral outcomes across multiple validated assays. By comparing various CRS parameters, we...
Intimate partner violence (IPV) poses a significant medical concern, predominantly affecting females. IPV-related brain injuries (IPV-BI), such as mild traumatic brain injury (mTBI) and non-fatal strangulation (NFS), sustained during physical attacks are common and often repetitive. Chronic neurobehavioral sequalae from IPV-BI are associated with neuroinflammation and impaired neuroplasticity,...
Psychotic disorders, such as schizophrenia and bipolar disorder, pose significant diagnostic challenges with major implications on mental health. The measures of resting-state fMRI spatiotemporal complexity offer a powerful tool for identifying irregularities in brain activity. To capture global brain connectivity, we employed information-theoretic metrics, overcoming the limitations of...
Approximately 30% of patients with depression suffer from treatment-resistant depression (TRD). Ketamine has shown antidepressant efficacy for TRD. While glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) has been demonstrated to play crucial roles in the process of pharmacological action of ketamine in experimental animals, it remains elusive how ketamine exhibits...
Classical psychedelic drugs show promise as a treatment for major depressive disorder and related psychiatric disorders. This therapeutic efficacy stems from long-lasting psychedelic-induced neuroplasticity onto prefrontal cortical neurons and is thought to require the postsynaptic expression of serotonin 2A receptors (5-HT_2AR). However, other cortical regions such as the granular...
Disruptions in sleep, circadian rhythms, and neural plasticity are closely linked to the pathophysiology and treatment of depression. Acute sleep deprivation (SD) produces rapid but transient antidepressant effects, yet the underlying mechanisms remain poorly understood. Using a mouse model of stress-induced depression, we found altered sleep architecture, impaired sleep homeostasis, and...
Molecular PsychiatryFebruary 18, 2026Marie Huc, Sara Siddiqi, Mysa Myers et al.1 citation
Esketamine has emerged as a fast-acting antidepressant option for individuals with treatment-resistant depression (TRD). Yet, little is known about how sex-assigned-at-birth shapes symptom-specific responses to these interventions, a critical gap in the move toward precision psychiatry. To address this gap, we conducted a pooled analysis of five randomized, double-blind, placebo-controlled...
should have read "Overall, our research implicates the 5-HT1BR, a nonhallucinogenic serotonin receptor, as a potential mediator of the behavioral and neural effects of psilocybin in mice."The final sentence of the Introduction should have read "Our findings suggest that the 5-HT1BR influences brain-wide neural changes following psilocybin administration and may contribute to its enduring...
As psychedelic-assisted psychotherapy gains momentum, clinical investigation of next-generation psychedelics may lead to novel compounds tailored for specific populations. 2,5-dimethoxy-4-bromophenethylamine (2C-B) is a psychedelic phenethylamine reported to produce less dysphoria and subjective impairment than the psychedelic tryptamine psilocybin. Despite its popularity among recreational...
Psychedelics, particularly psilocybin, have garnered significant attention as potential therapeutic tools for treating substance use disorders (SUDs), such as those related to alcohol, nicotine, heroin (an opioid), or cocaine. Traditional treatments often fall short, leading to high relapse rates and an urgent need for innovative approaches. This article explores the emerging role of...
Ketamine was shown to promote synaptogenesis, which is thought to account for its antidepressant effects through the restoration of lost synaptic connections observed in depression. PET imaging using 11C-UCB-J, a radiotracer targeting the synaptic vesicle protein 2 A (SV2A), was investigated as a translational method to monitor ketamine-induced changes in synaptic density in the corticosterone...
Molecular PsychiatryNovember 18, 2025A. Arena, M. R. Rubinstein, A. M. Genaro et al.
Ketamine has emerged as a rapid and sustained treatment for Major Depressive Disorder (MDD) and an alternative for patients who have not responded to traditional therapies. Its effects have been partly attributed to the noncompetitive antagonism of the N-methyl-D-aspartate receptor (NMDAR) in the central nervous system, which enhances neuroplasticity. However, the etiopathology of MDD is...
Psychedelics have garnered significant interest for their therapeutic potential in mental health conditions such as depression, anxiety, and post-traumatic stress disorder. While research has primarily focused on well-studied psychedelics, phenethylamine derivatives have also gathered interest for their potential therapeutic applications. Thus, this study aims to investigate the pharmacological...
Abstract Various ring-substituted α-methylphenethylamines (i.e., amphetamines) produce psychedelic-like effects that are primarily mediated by activity at 5-hydroxytryptamine 2A (5-HT 2A ) receptors. Small lipophilic substituents at the 4-position of the 2,5-dimethoxyamphetamine core structure can greatly enhance the clinical potency of such derivatives. Here, we studied the effects of various...
Current first-line antidepressants, such as selective serotonin reuptake inhibitors (SSRI), often present a delayed onset of action and fail to effectively treat a large proportion of patients, leaving a gap in the treatment of mood disorders. Psychedelics have recently emerged as promising alternatives due to their ability to produce fast-acting antidepressant effects through neuroplastic...
Psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), ketamine, and N,N-dimethyltryptamine (DMT), have captured the attention of scientists, artists, and seekers alike for their profound ability to alter consciousness and inspire creativity. The concept of "creation" encompasses multiple interpretations-ranging from generating novel ideas to fostering personal transformation. This...
Studies of serotonergic or 'classic' psychedelics in nonhuman primates (NHPs) have provided valuable information about the drugs' effects on the brain and behavior in closely related species to humans. Psychedelics induce characteristic changes to both spontaneous and operant behaviors in NHPs, though variability exists in the different effects reported by different studies; this variability...
Abstract We quantify cellular- and circuit-resolution neural network dynamics following therapeutically relevant doses of the psychedelic psilocybin. Using chronically implanted Neuropixels probes, we recorded local field potentials (LFP) alongside action potentials from hundreds of neurons spanning infralimbic, prelimbic and cingulate subregions of the medial prefrontal cortex of...
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...
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 following part of the abstract had a minor error: ‘Following PT, there was greater activation in the ventromedial prefrontal cortex and sensory regions, and reduced activation in the angular gyrus.’ This is now corrected to ‘Following PT, there was decreased activation in the ventromedial prefrontal cortex and angular gyrus, and greater activation in sensory regions.’ The original article...
Empathy plays a crucial role in interpersonal relationships and mental health. It is decreased in a variety of psychiatric disorders including major depression. Psilocybin, a promising candidate for treating depression, has been shown to acutely increase emotional empathy in healthy volunteers. However, no study has investigated this effect and its relevance for symptom improvement in a...