Molecular Psychiatry
October 28, 2026
Haojiang Zhai, Hongshuang Wang, Yibo Wang et al.
Serotonergic psychedelics have revitalized psychiatric research by producing rapid and potentially sustained clinical benefits in selected neuropsychiatric conditions. However, the mechanisms linking receptor activation to neural plasticity, altered conscious experience, and clinical improvement remain incompletely understood, while the evolutionary origins of psychedelic signaling and the...
Molecular Psychiatry
October 3, 2026
Xiubo Du, Feiyuan Peng, Xiaohui Wang
Disorders of consciousness (DoC), including coma, unresponsive wakefulness syndrome (also known as vegetative state), and minimally conscious state, represent profound disruptions in awareness and responsiveness due to severe brain injury, with limited therapeutic options available. Recent advancements in neuroimaging have improved our ability to detect residual brain activity in DoC patients,...
Molecular Psychiatry
September 19, 2026
Dijia Wang, Junnan Xu, Zhaoran Wang et al.
Hallucinations are a core feature of several psychiatric disorders, but the circuit mechanisms that separate perception from behavioral output remain poorly defined. Here, we combined an auditory discrimination task with AI-based pose analysis to quantify S-ketamine-induced false auditory threat responses and behavioral disorganization in mice. Control assays, including sucrose preference, loss...
Molecular Psychiatry
September 17, 2026
James J Gattuso, Bilgenur Bezcioglu, Jenna Hendey et al.
Obsessive-compulsive disorder (OCD) remains difficult to treat, and evidence indicates that social dysfunction, common across obsessive-compulsive and related disorders, is an under-recognized clinical burden. SAPAP3 knockout (KO) mice, a well-established model of compulsive behavior, exhibit social abnormalities, suggesting broader disruptions in circuits relevant to social cognition. Here, we...
Molecular Psychiatry
September 2, 2026
Yunkai Sun, Yehong Fang, Pu Peng et al.
Marked interindividual heterogeneity in substance use disorder (SUD) impedes the identification of consistent neuroanatomical alterations, limiting the development of robust markers for clinical risk stratification. We applied a normative modeling framework to explore individual neuroanatomical deviations in individuals with SUD across two distinct substance classes, and assessed their...
Molecular Psychiatry
August 11, 2026
Psychedelics and astrocytes: a hypothesis-driven perspective on neuro-glial integration, network plasticity, and neuroimmune reprogramming.
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
August 3, 2026
A crucial cautionary note on frequently incorrect dose equivalence between ketamine and esketamine.
Molecular Psychiatry
July 28, 2026
Convergent neuroimmune signaling underlying rapid antidepressant response to ketamine and psychedelics.
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 7, 2026
Axel F. Rosado, Abigail L. Yu, Jen-Hau Yang et al.
Classic serotonergic psychedelics such as psilocybin act as agonists at cortical serotonin (5-HT) 2A receptors (5-HT 2A R), inducing psychedelic effects in humans and head-twitch responses (HTRs) in rodents. Another class of psychedelic drugs called entactogens, exemplified by MDMA, function primarily as monoamine releasers and typically evoke minimal HTR despite causing serotonin release. The...
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 11, 2026
Ritchy Hodebourg, Lillian Duncan, Eric Dereschewitz et al.
The rising legal acceptance of cannabis and the high comorbidity between cannabis use disorder (CUD) and post-traumatic stress disorder (PTSD) highlight the importance of understanding how stress and cannabis influence the brain. We recently discovered that cannabinoid use promotes two PTSD-like symptoms: avoidance coping behaviors and the generalization of stress-coping responses to a neutral...
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...