Current Neuropharmacology - Online First

Schizophrenia with substance use disorder is a complex clinical condition that may increase treatment resistance. Cannabis use disorder is frequently associated with psychosis and the causal link has still to be defined. Partial D2/3 agonists may ensure limbic dopamine release normalization while avoiding reduced frontocortical dopamine release, which would contribute to negative symptoms. We aimed to observe the clinical course of patients with schizophrenia comorbid with cannabis use disorder while being treated with oral or long-acting injectable D2/3 partial agonists.

We observed 96 young adults with schizophrenia/schizoaffective disorder comorbid with cannabis use disorder during 18 months of treatment with aripiprazole long-acting injectable or oral aripiprazole or brexpiprazole. The assessment comprised Clinical Global Impressions-Severity, Positive And Negative Syndrome Scale, Brief Psychiatric Rating Scale, Barratt Impulsiveness Scale, and Visual Analog Scale for Craving.

Included were 17 women and 79 men (mean age = 26.89 ± 4.74 years). The sample responded favorably to treatment as assessed by all clinical scales, save for the impulsiveness scale which showed no significant change. The four treatment samples responded well without differences, but employing a general linear model, long-acting injectable aripiprazole and brexpiprazole were better and similar on all clinical and craving scales compared to oral aripiprazole and to other antipsychotics. Long-acting injectable aripiprazole fared better than brexpiprazole on general psychopathology, negative symptoms, and craving, while the reverse was true for global severity. However, the sample size imbalance did not allow for drawing strong conclusions. We found no significant treatment resistance in our 96-patient sample.

Partial D2/3 agonists may treat comorbid schizophrenia/schizoaffective disorder and cannabis use disorder, improving the symptoms of both disorders and substance craving.

Today more and more people search the web for health-related information, risking to come across misinformation and biased content that may affect their treatment decisions. Cannabidiol (CBD) is among the products for which beneficial effects have been claimed, often at the expense of the risks; further keeping in mind unreliable information reported on products themselves.

This study evaluated the quality of information retrieved by Google on the potential effects of CBD on weight management, also comparing Italian and English contents, hypothesizing generally low quality and language-driven differences in offered information.

Queries regarding cannabidiol and obesity-related terms were entered into Google, ranking the first 50 webpages from both merged Italian and English results for analysis.

Of the outputs, 37 Italian and 27 English websites addressed the topic and were not related to medical literature. As expected, a substantial proportion of information was of low quality, with English sites performing better (29.6%) than Italian ones (54%, p = 0.052) in terms of “JAMA benchmarks” for trustworthiness of information. Also, while most English sites were “Health portals” (40.7%) with neutral stance toward CBD (74.1%), Italian ones were predominantly “commercial” (78.4%, p = 0.001) and promoting CBD use (89.2%, p < 0.001).

Findings suggest the need for better online information, especially in non-English-speaking countries, as scarce and unequal information can lead people to make poor health choices, with potentially harmful consequences.

The study demonstrates that pharmacological blockade of type 3 metabotropic glutamate (mGlu3) receptors at the time of tumor induction significantly reduces the incidence of brain gliomas in rats. The overall survival of patients with high-grade brain gliomas is 14-20 months after current multimodal therapy, including surgery, radiotherapy, and adjuvant chemotherapy.

To demonstrate in this experimental model that pharmacological blockade of group II metabotropic glutamate receptors reduces the incidence of brain tumors induced by prenatal exposure to N- ethyl-N-nitrosourea (ENU) in rats.

Dams received a single injection of ENU (40 mg/kg, e.v.) at day 20 of pregnancy, combined with 5 daily injections of either saline or the mGlu2/3 receptor antagonist, LY341495 (10 mg/kg) (from day 15 to day 21 of pregnancy). Assessment of brain tumors in the offspring at 5 months of age showed the presence of mixed gliomas (astrocytomas/oligodendrogliomas) in 70% of the ENU + saline group of rats and only in 30% of the ENU + LY341495 group.

Tumors in both groups of rats showed a moderate/high expression of the astrocyte marker, GFAP, and the oligodendrocyte marker, OLIG-2, and a low expression of the proliferation marker, Ki-67. However, tumors of the ENU + LY341495 group showed a reduced density of Iba-1⁺ cells, suggesting a lower extent of neuroinflammation in the tumor microenvironment. These findings strengthen the hypothesis that mGlu3 receptors are candidate drug targets for the treatment of malignant gliomas.

Most electroencephalographic (EEG) investigations on alcohol have focused on adults, and scarce data is available about the potential of EEG measurements to detect young people at high-risk, as well as, to understand possible sex differences in alcohol impact on the brain.

This systematic review aimed to explore sex-related differences in EEG among young people with alcohol misuse, alcohol use disorder (AUD), and offspring of families with AUD.

A systematic review of the literature was conducted following PRISMA guidelines. Review protocol was registered in Prospero (ID: CRD42024511471). After article selection process and quality assessment, 25 studies were included in our review. The search included participants between 12 and 30 years old with problematic alcohol consumption, as defined by DSM, AUDIT, or specific alcohol misuse questionnaires.

It seems that beta was generally higher in young males with AUD, and they usually exhibited greater interhemispheric connectivity (interHC), whereas young females with AUD tended towards enhanced intraHC. P3 appears to be particularly sensitive to alcohol misuse, with males typically exhibiting a lower amplitude than young females. Other event related potentials (ERPs) such as N415, P640, and the error-related negativity (ERN) lacked sufficient methodological support to draw conclusions regarding sex differences, N340 and P540 suggested avenues for expanding research on memory processing, indicating differences in amplitude between males and females.

Considering sex variables in clinical research will enhance our understanding of alterations in brain function and structure with the goal of tailoring treatment strategies for AUD.

The heterogenicity in Alzheimer's Disease (AD) progression hinders individual prognosis. The present work is an observational 2-year longitudinal study in patients with mild cognitive impairment due to AD (n= 52, with positive CSF biomarkers). The aim of this study is to predict which patients are at risk of fast progression. For this, 3 neuropsychological tests based on different domains (clinical dementia, cognition, delayed memory) and the sum of them were used.

The tests were performed at diagnosis time (T1) and two years after the diagnosis time (T2). Then, the corresponding progression models were developed using each individual test and their sum as a variable response.

As a result, the model based on cognition status to predict fast decline (differences in the Z score (T2-T1) <1.5 were considered fast declining) provided satisfactory performance (AUC 0.74, 83.3% of sensibility and 70.2% of specificity); the models based on clinical dementia and delayed memory to predict fast declining showed low AUC and sensitivity. Nevertheless, the model based on the sum of the 3 tests showed the highest AUC (0.79), low sensitivity (63.6%), and high specificity.

The developed progression models could provide useful information to clinicians and AD patients regarding their fast/normal decline in general or specific domains.