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Cannabidiol (CBD) is a promising neurological agent with potential beneficial effects on memory and cognitive function. The combination of CBD and topiramate in the treatment of some neurological diseases has been of great interest. Since Topiramate-induced memory loss is a major drawback of its clinical application and the overall effect of the combination of CBD and topiramate on memory is still unclear, here we investigated the effect of CBD on topiramate-induced memory loss and the underlying molecular mechanisms. A one trial step-through inhibitory test was used to evaluate memory consolidation in rats. Moreover, the role of N-methyl-D-aspartate receptors (NMDARs) in the combination of CBD and topiramate in memory consolidation was evaluated through the intra-CA1 administration of MK-801 and NMDA. Western blot analysis was used to evaluate variations in brain-derived neurotrophic factor (BDNF) and phosphorylated cyclic AMP response element-binding protein (pCREB)/CREB ratio in the prefrontal cortex (PFC) and hippocampus (HPC). While the intraperitoneal (i.p.) administration of topiramate (50, 75, and 100 mg/kg) significantly reduced inhibitory time latency, the i.p. administration of CBD (20 and 40 mg/kg) could effectively reverse these effects. Similarly, the sub-effective doses of NMDA plus CBD (10 mg/kg) could improve the topiramate-induced memory loss along with an enhancement in BDNF and pCREB expression in the PFC and HPC. Contrarily, the administration of sub-effective doses of the NMDAR antagonist (MK-801) diminished the protective effects of CBD (20 mg/kg) on topiramate-induced memory loss associated with decreased BDNF and pCREB levels in the PFC and HPC. These findings suggest that CBD can improve topiramate-induced memory impairment, partially by the NMDARs of the PFC and HPC, possibly regulated by the CREB/BDNF signaling pathway., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Identification of distinct genetic and epigenetic profiles in various neuroepithelial tumors has improved the classification and uncovered novel diagnostic, prognostic, and predictive molecular biomarkers for improved prediction of treatment response and outcome. Especially, in pediatric high-grade brain tumors, such as diffuse midline glioma, H3K27M-altered and posterior fossa group A-ependymoma, epigenetic changes predominate, along with changes in expression of known oncogenes and tumor suppressor genes induced by histone modifications and DNA methylation. The precise role of epigenetic abnormalities is important for understanding tumorigenesis and the establishment of brain tumor treatment strategies. Using powerful epigenetic-based therapies for cancer cells, the aberrantly regulated epigenome can be restored to a more normal state through epigenetic reprogramming. Combinations of agents targeting DNA methylation and/or other epigenetic modifications may be a promising cancer treatment. Therefore, the integration of multi-omics data including epigenomics is now important for classifying primary brain tumors and predicting their biological behavior. Recent advances in molecular genetics and epigenetic integrated diagnostics of brain tumors influence new strategies for targeted therapy., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Adolescence is period characterized by sexual development, increasing romantic relationships, and the initiation of sexual activity. To enhance the exploration of their sexuality, adolescents may look into sexual resources such as pornography. There has been little research in India to understand how much adolescents are exposed to Internet pornography and what are the associated risk factors. This study examined the level of exposure to pornography among adolescents and the associated factors which determine the exposure to pornography in Uttar Pradesh and Bihar. Understanding the Lives of Adolescents and Young Adults (UDAYA) survey data collected in 2015-2016 was used for this study. The study was based on 3885 adolescent boys and 7766 adolescent girls aged 15-19 years. The mean age for adolescent boys was 16.66 years (SD: 1.3), and for girls it was 16.67 years (SD: 1.3). About 47% of adolescent boys but only 6% of girls were exposed to pornography. The likelihood of exposure to pornography was 1.69 times and 2.27 times more likely among adolescents and girls who had their own personal mobile phones, respectively, compared to those who did not have their own personal mobile phones. The odds of exposure to pornography were significantly higher among adolescent boys who had frequent media exposure than those who had no/rare exposure. Programs on life skills and comprehensive sexuality education need to be prioritize., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to evaluate the effectiveness of the drug and violence resistance educational program (PROERD) on short-term secondary outcomes, such as intentions to use drugs, attitudes toward drugs, school experience, and life skills (refusal, decision-making, and communication). Two cluster-randomized controlled trials were conducted in 30 public schools in the city of São Paulo (Brazil) with 4030 students (1727 fifth and 2303 seventh graders). The intervention group attended 10 PROERD classes conducted by trained police officers, whereas the control group received no intervention. PROERD is a Brazilian adaptation of the North American Drug Abuse Resistance Education (DARE) program Keepin' it REAL. Data were collected at two time points: pre-intervention and at 9-month follow-up. Two different paradigms were used in the multilevel analysis, complete case (CC), and intention-to-treat (ITT) analyses, using full information maximum likelihood (FIML). We found mixed results. Although the seventh-year curriculum seems to have positive effects on school experience (coef = 0.093; 95% CI: 0.001, -0.185), it also increases the intention to use cigarettes in the future (OR = 1.93, 95% CI: 1.109, 3.379) and the chances of accepting marijuana (OR = 1.62, 95% CI: 1.03, 2.53), and it appears to slightly reduce decision-making skills among fifth graders (coef = -0.078; 95% CI: -0.131, -0.025). Our results suggest that PROERD implementation and cultural adaptation should be reevaluated to understand why the program does not achieve the expected preventive goals and produces potential iatrogenic effects., (© 2021. Society for Prevention Research.)

Sexual risk behaviors are closely related to the use of alcohol, tobacco, and other illicit drugs as well as teen dating violence. School-based drug prevention programs that teach social and personal skills could potentially also reduce sexual risk behaviors. We examined the effects of the #Tamojunto program on youth sexual risk behaviors. A randomized controlled trial was conducted with 6391 7th and 8th grade students in 72 public schools in six Brazilian cities. Baseline data were collected prior to program implementation. Two waves of follow-up assessments occurred after 9 and 21 months. Analyses were performed taking into account the multilevel structure of the data. We used intention-to-treat to evaluate changes in the prevalence of sexual risk behaviors over time and between groups. Adolescent age ranged from 11 to 15 years, with a mean of 12.6 ± 0.8 years, and 51.0% were female. Among all participants, receipt of #Tamojunto was associated with higher risk of lifetime sex at 21 months follow-up (OR 1.27, 95% CI [1.03, 1.56]). Among girls, at 9 months follow-up, the program was associated with higher likelihood of having engaged in sex in the last month (OR 1.76, 95% CI [1.13, 2.74]). At 21 months follow-up, girls receiving the program were more likely to report engaging in condomless sex in the last month (OR 1.64, 95% CI [1.07, 2.50]). #Tamojunto may be ineffective and possibly harmful for preventing sexual risk behaviors, especially among girls. We suggest further investigation of the possible mediating role of life skills intervention components on girl's sexual behaviors., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The global march towards legalization of marijuana consumption is pursued in reason of the supposed harmless properties of this plant. Actually, a wide range of cannabinoids is endogenously produced and interacts with different classes of receptors ubiquitously distributed in the human body. Such endocannabinoid system (ECS) modulates several functions in health and disease. However, studies on synthetic ligands with selective agonist/antagonist activity on specific cannabinoid receptors, have clarified how complex the cannabinoid system is. The whole biological activity of cannabis sativa remains difficult to establish, due to the fact that it is a complex mixture of phytocannabinoids with different or even opposing effects. Δ9-tetrahydrocannabinol is the most represented phytocannabinoid in the marijuana plant and then the most studied compound. It has been widely associated with adverse CV effects in marijuana smokers. Conversely, less is known about the role of other phytocannabinoids. Here, we summarized the current knowledge about the effects of phytocannabinoids in CV disease, mainly focusing on atherosclerosis and myocardial infarction. We critically discussed clinical and experimental evidence linking phytocannabinoids to CV disease, attempting at explaining some controversies and suggesting the direction for future studies.

The testis is one of the organs in the mammalian body that is sensitive to toxicants. Accumulating evidence has shown that human exposure to toxic ingredients in Traditional Chinese Medicine (TCM), such as triptolide, gossypol, cannabidol, piperine, α-solanine, matrine, aristolochic acid, and emodin, lead to testis injury and reproductive dysfunction. The most obvious phenotype is reduced sperm counts due to defects in spermatogenesis. Studies have also shown that Sertoli cells in the seminiferous tubule, the functional unit of the testis that supports spermatogenesis, are the cell type that is most sensitive to the disruptive effects of toxicants. Since Sertoli cells are the "mother cells" that nurture germ cell development, Sertoli cell injury thus leads to failure in germ cell development in the seminiferous epithelium. Mounting evidence has shown that the Sertoli cell cytoskeletons, mitochondria function, Leydig cells steroidogenesis pathways and sperm ion channels are some of the prime targets of toxicants from TCM. We carefully evaluate recent findings in this area of research herein, and to provide a summary of these findings, including some insightful information regarding the underlying molecular basis of toxicant-induced testis injury that impede spermatogenesis., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Cannabis-derived cannabinoids have neuroactive properties. Recently, there has been emerging interest in the use of cannabidiol (CBD)-enriched products for treatment of drug-resistant epilepsy. In 2018, the FDA approved the use of CBD-rich Epidiolex for two severe forms of epilepsy in children (Lennox-Gastaut and Dravet syndromes). Experimental research supports the use of CBD in many CNS disorders, though the mechanisms underlying its anticonvulsant and neuroprotective effects remain unclear. CBD has been shown to reduce inflammation, protect against neuronal loss, normalize neurogenesis, and act as an antioxidant. These actions appear to be due to the multimodal mechanism of action of CBD in the brain. This chapter briefly describes the current information on cannabis pharmacology with an emphasis on the clinical utility of CBD in the treatment of refractory epilepsies and other related seizure conditions. Clinical trials are ongoing for other forms of epilepsy and refractory seizures associated with infantile spasms, tuberous sclerosis, and Rett syndrome. Overall, adjunct CBD has been found to be generally safe and effective for treatment-resistant seizures in children with severe early-onset epilepsy. Whether an add-on CBD is efficacious for the long-term treatment of various epilepsy and seizure types in adults being tested in various clinical trials.