Abstract: Eating disorders are complex mental health disorders characterized by persistent changes in eating behaviour, cognition, emotion, and physiological regulation. Psychological therapies remain the mainstay of treatment; however, clinical outcomes are often heterogeneous, with a sizeable proportion of individuals experiencing partial recovery or relapse. This has renewed interest in pharmacological approaches that extend beyond symptom control to target underlying neurobiological mechanisms. This review discusses emerging pharmacological approaches informed by advances in the understanding of reward processing, stress responsivity, metabolic signalling, and gut–brain interactions in eating disorders. Evidence from clinical and translational studies suggests that selected agents may reduce binge-eating frequency, compulsive drive, and dysregulated appetite. However, findings remain inconsistent and are often limited by small sample sizes and short follow-up periods. Crucially, clinicians must consider psychological and social contexts when interpreting the clinical effects of these medications. Patients may experience changes in hunger, weight, or emotional processing differently, which may influence treatment adherence and perceived treatment effects. Methodologically rigorous studies, improved patient classification, and outcome measures that capture functional recovery and quality of life should be prioritized in future research. Pharmacotherapy is most likely to be effective when administered within a personcentered framework and integrated with psychological therapies.
Introduction: The behavioral sensitization (BS) model for psychostimulants is the most developed framework for explaining the occurrence of drug-induced psychoses. However, there is limited data on the potential of synthetic cathinones (SCs) to induce BS, which restricts the model’s full application in understanding this phenomenon. Aim: This study aimed to provide theoretical evidence regarding the potential of synthetic cathinones to inhibit the dopamine membrane transporter at levels sufficient to induce behavioral sensitization. Methods: The following SCs were selected as ligands: 4-methylmethcathinone (mephedrone), 3,4- methylenedioxypyrovalerone (MDPV), and alpha-pyrrolidinovalerophenone (alpha-PVP). Amphetamine and cocaine were included for comparison. Molecular docking was performed using Auto- Dock Vina and the Attracting Cavities algorithms. The human dopamine transporter structure was obtained from the Protein Data Bank (PDB ID: 8Y2DS). Additionally, PubMed, CNKI, and eLibrary databases were searched to compare the docking results with experimental data from cell lines and animal studies; 13 publications were included in the analysis. Results: All synthetic cathinones studied showed no significant differences in binding affinity to the orthosteric site of the dopamine membrane transporter, suggesting that they may act similarly to amphetamine and cocaine. These findings were corroborated by experiments in cell lines. For mephedrone and MDPV, the potential to induce behavioral sensitization (BS) was also confirmed in animal studies. Conclusion: Theoretically, mephedrone, MDPV, and alpha-PVP can inhibit the dopamine membrane transporter, leading to increased extracellular dopamine levels and promoting the development of dopamine hypersensitivity and behavioral sensitization.
Abstract: Neuro-psychiatric disorders represent one of the most complex and pressing challenges in modern medicine. These conditions, ranging from schizophrenia and Parkinson’s disease to Alzheimer’s and mood disorders, are characterized by multifactorial etiologies, overlapping symptomatology, and often unpredictable therapeutic responses. Despite decades of research, the pharmacological management of these disorders remains suboptimal, with many patients experiencing limited efficacy, delayed onset of action, or debilitating side effects. A growing body of evidence points to shared pathological mechanisms across neurodegenerative and psychiatric conditions, including intracerebral protein aggregation, mitochondrial dysfunction, abnormal iron accumulation, oxidative stress, and ferroptosis-induced neuronal death. These converging pathways underscore the need for therapeutic strategies that go beyond symptomatic relief to address underlying molecular dysfunctions. In this context, this thematic issue brings together a collection of cutting-edge research articles that reflect the latest advances in drug design, development, and delivery strategies to improve therapeutic outcomes in neuropsychiatric care. This issue is a curated effort to bridge the gap between molecular innovation and clinical translation. It highlights how interdisciplinary approaches spanning medicinal chemistry, pharmacogenomics, molecular docking, and natural product research are converging to redefine the therapeutic landscape. From enzyme-targeted therapies and marine-derived neuroprotectants to prolactin-sparing antipsychotics and precision medicine frameworks, each manuscript contributes a unique perspective to this evolving field. Collectively, these studies illuminate promising avenues for personalized, mechanism-based interventions that may transform the future of neuropsychiatric treatment. This issue aspires to serve not only as a scholarly resource but also as a catalyst for innovation and collaboration across disciplines.
Background: Scutellarein, a bioactive flavone derived from Scutellaria barbata D. Don—a herb widely used in Traditional Chinese Medicine (TCM)—is known for its neuroprotective, neurogenic, and anti-inflammatory properties. Our previous research demonstrated that the hydroethanolic extract of S. barbata (HSBE) exhibits robust antidepressant-like activity, supported by behavioral, neurochemical, and biochemical alterations in rodent models. Furthermore, a validated High-Performance Thin-Layer Chromatography (HPTLC) method confirmed the presence of scutellarein in significant amounts within the extract. Based on these findings and existing literature, the present study was designed to investigate the antidepressant-like potential of scutellarein and elucidate its molecular mechanisms. Method: Swiss albino mice were orally administered scutellarein at doses of 20 and 40 mg/kg body weight for three weeks. The CUMS method was employed to induce depression for 21 days. On the 21st day, TST, FST, and OFT were used to evaluate antidepressant-like potential. On the 22nd day, 5-HT, NE, and DA levels were quantified in the cortex, hypothalamus, and hippocampus. MAO-A and B activity, as well as levels of antioxidant enzymes, were assessed in the brain. Additionally, plasma corticosterone and nitrite levels were also measured to elucidate the mechanisms of action. Results: Scutellarein exhibited dose-dependent antidepressant-like effects in both TST and FST, with enhanced locomotor activity observed in the OFT, indicating improved mood and mobility. Furthermore, scutellarein significantly modulated levels of NE, 5-HT, and DA in key brain regions. Additionally, it regulated MAO-A and B activity, as well as antioxidant enzyme levels, potentially affecting neurotransmitter levels and mitigating oxidative stress. Scutellarein also affected plasma nitrite and corticosterone levels, indicating systemic impact on nitric oxide signaling and the HPA axis, which are key in stress responses. Discussion: The findings suggest that scutellarein exerts antidepressant-like effects through a multimodal mechanism involving monoaminergic regulation, attenuation of oxidative and nitrosative stress, inhibition of MAO activity, and modulation of HPA axis function. These combined actions support the neurobiological relevance of scutellarein in stress-induced depression. Conclusion: Scutellarein demonstrates significant antidepressant-like activity in vivo and may represent a promising phytochemical candidate for further development as a novel antidepressant agent.
Introduction:: Emotional blunting—i.e., a subjective reduction in emotional range and intensity—is frequently reported during SSRI treatment and may hinder full functional recovery in major depressive disorder (MDD). Esketamine, a rapid-acting glutamatergic antidepressant approved for treatment-resistant depression (TRD), may exert antidepressant benefits while preserving emotional responsiveness. Methods:: We conducted a two-arm, naturalistic observational study including 60 adults with TRD (SSRI monotherapy, n=30; adjunctive intranasal esketamine, n=30). Emotional blunting and emotional intensity were assessed at baseline and week 4 using the Oxford Depression Questionnaire (ODQ), the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants (OQESA), the Laukes Emotional Intensity Scale (LEIS), and the Self-Assessment Manikin (SAM). Depressive symptoms were measured with the Montgomery–Åsberg Depression Rating Scale (MADRS). Between- group comparisons used independent-samples t-tests with effect-size estimation. Results:: Both groups improved in depressive symptoms, with a significantly greater MADRS reduction in the esketamine group (−16.7 vs −5.4 points; p< 0.0001). Compared with esketamine, SSRI-treated patients reported higher emotional blunting (ODQ and OQESA; p< 0.0001) and lower emotional intensity/valence (LEIS and SAM; p< 0.0001). Discussion:: Adjunctive esketamine was associated with both superior antidepressant improvement and a more preserved emotional experience than SSRI monotherapy. Conclusion:: In TRD, adjunctive intranasal esketamine was associated with reduced emotional blunting and greater symptom improvement versus SSRI monotherapy, supporting routine assessment of emotional side effects in treatment planning.
