Molecular Psychiatry
August 4, 2026
Kim P. C. Kuypers, Natasha L. Mason, Aurelie Carlier et al.
Women experience a disproportionate burden of affective and stress-related disorders, with symptom variability shaped by endocrine transitions across the menstrual cycle, pregnancy, postpartum, and menopause. Although psychedelic-assisted therapies are increasingly investigated for these conditions, hormonal state represents a largely unaccounted determinant of variability in exposure,...
Molecular Psychiatry
July 16, 2026
Marco Taddei-Tardón, Lidia Medina-Rodríguez, Jessica L Maltman et al.
Serotonergic psychedelics have attracted considerable interest as promising therapeutic agents. However, the molecular mechanisms linking their acute hallucinogenic-like effects to longer-lasting neuroplastic responses remain incompletely understood, partly because of the scarcity of native neural models suitable for mechanistic studies. Here, we developed a neural stem cell-derived in vitro...
Molecular Psychiatry
July 10, 2026
Cong Lin, Xiaohui Wang
Classic psychedelics such as lysergic acid diethylamide (LSD), psilocybin, N,N-dimethyltryptamine (DMT), and mescaline induce lasting changes in neuroplasticity and behavior that extend far beyond their acute pharmacological effects. Emerging evidence highlights that these enduring therapeutic benefits in neuropsychiatric conditions may be significantly mediated through complex epigenetic...
Molecular Psychiatry
July 8, 2026
Granville J. Matheson, Johan Lundberg, Martin Gärde et al.
The serotonin 1B receptor can be studied in vivo with PET using [^11C]AZ10419369, and has been linked to both the pathophysiology and treatment of major depressive disorder (MDD). Ketamine and electroconvulsive therapy (ECT) both exert rapid and potent antidepressive effects, and although these treatments may not act directly on the serotonin system, they both cause dose-dependent increases in...
Molecular Psychiatry
July 3, 2026
Yu Wang, Ji-Tao Li, Lin-Lin Zhu et al.
Despite its high prevalence, the precise mechanisms underlying major depressive disorder (MDD) remain incompletely understood. Growing evidence identifies mitochondrial dysfunction, including abnormalities in mitochondrial DNA, impaired bioenergetics, disrupted quality control, and redox imbalance, as a central pathological feature of MDD. Beyond deficits in energy production, mitochondria...
Molecular Psychiatry
July 1, 2026
Waki Nakajima, Tetsu Arisawa, Susumu Jitsuki et al.
1 citation
Subanesthetic doses of ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, produce rapid and robust antidepressant effects in patients with treatment-resistant depression (TRD). However, after a single administration, the therapeutic benefit is short-lived, and strategies to maintain its efficacy remain unclear. This study focused on the glutamate...
Molecular Psychiatry
June 27, 2026
David R. Roalf, Tyler M Moore, Jacquelyn Stifelman et al.
Abstract Cannabis use is linked to elevated psychosis risk, yet the neurobiological mechanisms that couple use to symptom expression remain unclear. Because glutamatergic dysregulation has been implicated in both cannabis effects and psychosis vulnerability, we examined whether brain glutamate relates to dimensional symptoms as a function of cannabis use across the psychosis spectrum....
Molecular Psychiatry
June 25, 2026
Clotilde Guidetti, Maurizio Fava, George I. Papakostas
Major depressive disorder (MDD) and treatment-resistant depression (TRD) are prevalent and debilitating conditions. Over 50% of patients have inadequate response to first-line serotonergic antidepressants and are left with suboptimal treatment options. Rapid-acting and individually tailored treatments for MDD remain major unmet needs. This review discusses promising rapid-acting treatments,...
Molecular Psychiatry
June 1, 2026
Charles F Zorumski, Joseph Cichon, Yukitoshi Izumi et al.
5 citations
The success of ketamine, a dissociative anesthetic and non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, as a rapidly acting antidepressant has ignited efforts to identify other novel depression treatments. In recent years, several clinical trials indicated that nitrous oxide (N2O), an inhalational dissociative anesthetic in clinical use for over 150 years, also has rapid and...
Molecular Psychiatry
June 1, 2026
Xin Yi, Yuan-Bo Zhang, Tong-Zhou Yu et al.
Post-traumatic stress disorder (PTSD) persists when stress biases memory systems-broadening threat engrams, weakening context-appropriate inhibition, and rendering extinction fragile. Integrating preclinical and human evidence, we argue that these liabilities are tractable within a circuit-informed framework that aligns behavioral procedures with the biology of fear memory. Extinction can be...
Molecular Psychiatry
May 29, 2026
Mickael Eskinazi, Rayan Nasserdine, Romane M Cusin et al.
Serotonergic psychedelics are increasingly investigated as treatments for affective disorders. Concerns persist regarding their potential to induce hypomania or mania, particularly in individuals with bipolar spectrum vulnerability. Whether these substances precipitate transient mood switches or contribute to persistent bipolar illness or diagnostic transition remains unclear. We conducted a...
Molecular Psychiatry
May 13, 2026
Fukang Zhang, Shuyuan Fan, Shiqi Li et al.
Nitrous oxide (N2O) is a frequently used recreational drug with significant addictive potential. The ventral tegmental area (VTA) is a key brain region associated with the rewarding effects of drugs of abuse. However, how N2O influences VTA functions to mediate reward-related behavior remains poorly understood. We reported that exposure to 60% N2O, but not 30%, effectively induced conditioned...
Molecular Psychiatry
May 1, 2026
Sixtine Fleury, Katherine M. Nautiyal
4 citations
Recent studies highlight the promising use of psychedelic therapies for psychiatric disorders, including depression. The persisting clinical effects of psychedelics such as psilocybin are commonly attributed to activation of the serotonin 2A receptor (5-HT2AR) based on its role in the acute hallucinatory effects. However, the active metabolite of psilocybin binds to many serotonin receptor...
Molecular Psychiatry
April 13, 2026
Xin Zhao, Xinyu Zhang, Shiying Yuan et al.
Ketamine, a potent N-methyl-D-aspartate receptor (NMDAR) antagonist, is widely used for anesthesia and analgesia and, because of its rapid antidepressant effects, in psychiatry. Increasing evidence suggests that ketamine and its enantiomers-(R)-ketamine (arketamine) and (S)-ketamine (esketamine)-also modulate systemic immunity and provide organ protection, partly through interactions with the...
Molecular Psychiatry
April 8, 2026
Johannes G. Ramaekers, Kim P. C. Kuypers, Franz X. Vollenweider
1 citation
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...
Molecular Psychiatry
April 8, 2026
Daniel Dautan, Anderson Camargo, P. Svenningsson
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 Psychiatry
April 1, 2026
Zijian 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...
Molecular Psychiatry
April 1, 2026
Josh Allen, Mujun Sun, Tamara L Baker et al.
1 citation
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,...
Molecular Psychiatry
April 1, 2026
Qiang Li, Jingyu Liu, Godfrey D Pearlson et al.
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...
Molecular Psychiatry
March 5, 2026
Waki Nakajima, Mai Hatano, Yohei Ohtani et al.
1 citation
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...
Molecular Psychiatry
March 1, 2026
Tyler G. Ekins, Chloe Rybicki-Kler, Tao Deng et al.
9 citations
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...
Molecular Psychiatry
March 1, 2026
Wilf Gardner, David H. Sarrazin, Martin Balzinger et al.
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 Psychiatry
February 18, 2026
Marie 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...
Molecular Psychiatry
February 12, 2026
Sixtine Fleury, Katherine M. Nautiyal
correction
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...
Molecular Psychiatry
February 3, 2026
Pablo Mallaroni, S. Parker Singleton, Natasha L. Mason et al.
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...