Current Neuropharmacology - Online First

The mechanisms of neurodegeneration common to many neurodegenerative diseases include oxidative stress, mitochondrial dysfunctions, excitotoxicity, and others. Beyond the broad spectrum of strategies for developing neuroprotective agents that target stage-specific mechanisms in each neurodegenerative disease, considerable attention is also being given to approaches aimed at developing compounds that can effectively modulate general pathogenic mechanisms and enhance the overall resilience of neuronal cells to cell death induction.

This review discusses some of the results on new multitarget multipharmacophore agents with neuroprotective effects, particularly through their influence on mitochondrial permeability transition and antioxidant properties. We conducted comprehensive online searches on PubMed to gather the latest data on multitarget multipharmacophore agents consisting of pre-defined pharmacophores that have already demonstrated neuroprotective properties.

To create compounds with a desirable spectrum of biological activity, an approach based on the conjugation of specific structural fragments of pharmacologically active substances into a single molecular entity could be used. Core fragments of compounds that have already demonstrated neuroprotective properties due to mitochondrial and antioxidant mechanisms of action can be used as neuroactive scaffolds.

The combination of several pharmacophores in one molecule may not only result in the mere addition of the useful properties of each component, but may also give rise to new types of biological activity. The examples of the appearance of new properties in such multipharmacophore compounds, not inherent in the reference agents, discussed in our review, may be considered a prospective approach for creating a novel generation of neuroprotective agents.

Preclinical and clinical studies reported that 3,4-methylenedioxymeth-amphetamine (MDMA, ‘ecstasy’) can cause adverse effects in the central nervous system (CNS). Recently, preclinical studies have demonstrated that certain psychoactive substances may exacerbate the noxious central effects of MDMA when co-administered, including substances that are contained as adulterants in tablets sold as MDMA in the illegal market. Since the quality and quantity of adulterants in tablets sold as MDMA vary based on factors, such as the year and the geographical region of production, this may result in diverse health risks for people who use MDMA.

This review provides a concise overview of: i) composition of tablets sold as MDMA in Continental Europe, UK, USA and Australia in the post COVID-19 pandemic period; ii) recent preclinical and clinical findings about the central effects of the psychoactive adulterants most commonly found in tablets sold as MDMA in the above areas; and iii) the possible adverse CNS effects of these adulterants in humans when taken in combination with MDMA.

We systematically searched PubMed, Scopus, and Web of Science for studies published between 2020 and 2025 using terms related to “adulterants”, “MDMA tablets composition,” “COVID-19”. Eligible articles were screened for quality, with emphasis on recent, high-impact contributions. Extracted papers included cytotoxicity studies, neurobehavioral outcomes, and mechanistic insights.

Tablets sold as MDMA are frequently and differently adulterated in Continental Europe, the UK, the USA, and Australia.

The possible interactions between MDMA and psychoactive adulterants contained in tablets sold as MDMA deserve attention, since they may potentially explain some of the noxious neurological and psychiatric effects that have been described in people who use MDMA.

Ongoing public health efforts and expansion of drug checking are essential to properly inform MDMA users about the risks associated with psychoactive contaminants, first responders, healthcare professionals, and the general public about the possible detrimental consequences for health associated with the use of MDMA obtained from illicit sources and unintended contaminant consumption.

Medical cannabis has gained growing attention as a potential treatment for children with Autism Spectrum Disorder (ASD), particularly in cases where conventional pharmacological approaches have proven ineffective. Emerging evidence suggests that cannabinoid-based therapies may alleviate Attention Deficit Hyperactivity Disorder (ADHD) related symptoms in children with ASD. The objective of this study is to evaluate changes in ADHD symptoms over six months of treatment with a CBD-rich cannabis oil, using the Conners' Teacher Rating Scale as the assessment tool.

This was a prospective, single-arm, open-label study conducted at a single center. A total of 109 children and young adults diagnosed with ASD and ADHD symptoms were recruited between November 2019 and April 2021. Of these, 53 participants were assessed by their schoolteachers using the Conners' Teacher Rating Scale (CTRS) questionnaire, both before and after a three- to six-month treatment period with a CBD-rich, cannabis oil-based product. Blood samples were collected before and after treatment to measure cannabinoid levels, including CBD, 6-OH-CBD, 7-COOH-CBD, and 7-OH-CBD.

Significant improvements were observed in the following categories: anxious-shyness, perfectionism, ADHD index, emotional lability, and hyperactivity-impulsivity (p < 0.001). Additional trends toward improvement were identified in oppositional behavior (p = 0.009), cognitive inattention (p = 0.009), hyperactivity (p = 0.006), the Conners’ Global Index (p = 0.007), and DSM-IV inattention scores (p = 0.003). No significant correlations were found between cannabinoid dosage or blood levels and changes in CTRS scores, except for emotional lability, where higher CBD concentrations were predictive of greater symptom improvement.

This is the first prospective study to evaluate the effects of CBD-rich cannabis on ADHD symptoms in children with ASD using standardized teacher-based Assessments (CTRS). The findings indicate improvements in core behavioral domains. While previous studies have focused primarily on parent-reported outcomes or small-scale trials, our results support emerging evidence on the role of cannabinoids in modulating attention and emotional regulation. The main limitations of the study were its open-label design.

CBD-rich cannabis oil may reduce ADHD symptoms in children with ASD. These findings support the need for future clinical trials to validate efficacy and determine optimal dosing.

To investigate hemodynamic and blood oxygen metabolism and their associations with disease progression, dopaminergic transporter (DAT) activity, and glucose uptake in patients with Parkinson’s disease (PD).

This cross-sectional study included 73 patients with PD (mean age: 61.10 years) and 67 healthy controls (mean age: 58.99 years). Oxygen metabolism parameters—deoxygenated hemoglobin (Cdeoxy), oxygen extraction fraction (OEFrel), deoxygenated cerebral blood volume (dCBV), and R2* were measured using qMRI. DAT availability and glucose metabolism were assessed using PET with [18F]FP-CIT and [18F]FDG, respectively. Regional analyses were conducted using standardized brain atlases.

Compared with the controls patients with PD exhibited elevated Cdeoxy, OEFrel, and R2* in the substantia nigra, whereas Cdeoxy and dCBV levels were reduced in the bilateral caudate nucleus and frontal cortex (p < 0.05). The Hoehn-Yahr (H-Y) 2.5–3 subgroup exhibited higher levels of Cdeoxy and OEFrel in the left putamen than the H-Y 1-2 subgroup (p < 0.05). In the H-Y 1-2 subgroup, Cdeoxy, OEFrel, and R2* correlated with UPDRS scores in the substantia nigra and red nucleus (p < 0.05). In advanced stages (H-Y stages 2.5-3), significant correlations were observed in the striatal structures/the left dorsolateral putamen/posterior right caudate (p < 0.05). OEFrel and R2* values were positively correlated with glucose metabolism in the left putamen and right caudate. (p < 0.05).

qMRI demonstrated alterations in hemodynamics and oxygen metabolism in patients with PD, particularly within the nigrostriatal system, suggesting that metabolic indicators could serve as supplementary biomarkers for diagnosing and monitoring the progression of PD.

Neural regeneration remains a highly debated topic, yet it lacks a systematic bibliometric analysis. The objective of this study is to utilize bibliometric methods to identify research trends and significant topics within this domain, thereby providing a comprehensive overview of the current state of knowledge in this field.

The Web of Science Core Collection (January 1, 2015 to October 3, 2024) served as the basis for analyzing 3,941 documents using CiteSpace and VOSviewer. The analysis focused on country/institution collaboration networks, keyword co-occurrence, and hotspot evolution.

Between 2015 and 2024, the number of publications in this field demonstrated an upward trend, characterised by fluctuations. China and the United States were the leading contributors to global research output, with China contributing 1,387 papers, accounting for 35.19% of the total, and boasting an H-index of 62. In contrast, the United States contributed 1,047 papers, with an h-index of 74. In recent years, research has been concentrated on four major technological directions, including neural electrical stimulation, biomaterial scaffolds, gene editing, and neural modulation.

This transformation in scholarly focus reflects the convergence of multiple catalytic factors, which have enabled the sophisticated simulation of neural systems, provided unprecedented analytical tools for neuroscience inquiry, and intensified societal demands for artificial intelligence applications and neurotechnology innovations, thereby stimulating accelerated research investment.

Over the past decade, researchers worldwide have focused on neural regeneration. Bibliometric analyses have assessed scholarship, identified research hotspots, summarized core concepts, and provided valuable insights for future research in this field.