Biomedicines
June 1, 2026
Masaru Tanaka
Major depressive disorder remains a leading cause of disability, and decades of monoamine-centered pharmacology have yielded delayed and often incomplete relief. Rapid-acting antidepressants reshaped the field by linking swift symptom improvement to glutamatergic plasticity, yet durable benefit depends on how newly reconfigured circuits are stabilized and tuned. This review synthesizes evidence...
Translational Psychiatry
May 29, 2026
Justyna K. Hinchcliffe, Katie Kamenish, Julia M. Bartlett et al.
Affective biases shape cognitive and emotional behaviour and are important in major depressive disorder (MDD). Modulation of affective biases by the NMDA antagonist, ketamine, may underlie its antidepressant effects but not all NMDA antagonists are efficacious. Some studies suggest ketamine's efficacy involves non-NMDA mechanisms e.g. via its active metabolite HNK (2R, 6R)-hydroxynorketamine),...
Biomedicines
May 23, 2026
Dominik Jucha, Michał Klimas, Dominika Wiśniewska et al.
Background/Objectives: Bipolar disorder affects about 40 million people worldwide, and the greatest burden of the disease is associated with depressive episodes. About 25% of patients experience drug-resistant depression, in which standard treatment turns out to be insufficient, and monotherapy often does not bring full remission. Despite the use of second-generation antipsychotics, the...
Zenodo (CERN European Organization for Nuclear Research)
May 17, 2026
Tenzin Trepp
preprint
Emerging research in contemplative science and psychedelic neuroscience suggests that deeply entrenched patterns of selfhood and cognition—often associated with mental disorders like depression—can be profoundly altered through both meditative practice and pharmacological intervention. This paper presents a neuroconstructivist framework for understanding how deep meditation and dissociative...
Cell
April 30, 2026
Hermany Munguba, Anisul Arefin, Ryota Hasegawa et al.
4 citations
Depression is driven by dysfunction in discrete neural circuits, but a deeper understanding of the underlying molecular and synaptic mechanisms is needed to guide the development of therapeutics. Here, we decipher the mechanisms of action of the fast-acting antidepressant ketamine to enable the identification of G protein-coupled receptor (GPCR) antidepressant targets. We find that the...
Naunyn-Schmiedeberg's Archives of Pharmacology
April 28, 2026
Yunsheng Liu, Rongde Zhong, Fenyong Yao et al.
Depression is a leading global health burden increasingly linked to dysregulation in glutamatergic signaling. Ionotropic glutamate receptors (iGluRs), including NMDA, AMPA, and kainate subtypes, have emerged as pivotal therapeutic targets. However, the rapid expansion of literature has led to a fragmented research landscape, creating an urgent need for a structured overview. This study aims to...
Pharmaceuticals
April 24, 2026
Pietro Carmellini, Alessandro Cuomo, Maria Beatrice Rescalli et al.
Background/Objectives: Major depressive disorder (MDD) remains a leading cause of disability worldwide and exhibits substantial biological heterogeneity that is not adequately captured by current symptom-based diagnostic systems. While the classical monoamine hypothesis has historically guided antidepressant development, it does not fully account for variability in treatment response, delayed...
bioRxiv (Cold Spring Harbor Laboratory)
April 7, 2026
Benjamin Hänisch, Tobias Kaufmann, Sofie L. Valk
preprint
Recent studies pioneered the use of classic hallucinogens as Rapid-Acting Antidepressants (RAAD). To further understand the link between their neuromodulatory and antidepressant effects, we combine pharmacodynamic profiles of four classic hallucinogens and the anaesthetic Ketamine with receptor density distributions from both Positron Emission Tomography (PET) and layer-resoluted...
Cureus
April 1, 2026
Juan Pablo Berlin Viniegra
Treatment-resistant depression (TRD) remains a major clinical challenge in psychiatric practice and affects a substantial proportion of patients with major depressive disorder (MDD). It is commonly defined as failure to achieve remission after at least two adequately conducted antidepressant trials. TRD is associated with persistent functional impairment, increased morbidity, reduced quality of...
Journal of Psychoactive Drugs
March 20, 2026
Marina A. M. Portes, Leandro J Bertoglio
Psilocybin, N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA) are psychedelic compounds with therapeutic potential for depression, anxiety, and post-traumatic stress. However, their relevance to endurance athletes, who face particular psychological and physical stressors, remains underexplored. This study combines a conceptual overview...