High cannabigerol hemp extract moderates colitis and modulates the microbiome in an inflammatory bowel disease model.

Cannabis sativa L. has a long history of medicinal use, particularly for gastrointestinal diseases. Patients with inflammatory bowel disease (IBD) report using cannabis to manage their symptoms, despite little data to support the use of cannabis or cannabis products to treat the disease. In this study, we utilize the well-described dextran sodium sulfate (DSS) model of colitis in mice to assess the impact of commercially available, non-euphorigenic, high cannabigerol (CBG) hemp extract (20 mg/mL cannabigerol, 20.7 mg/mL cannabidiol, 1 mg/mL cannabichromene) on IBD activity and the colonic microbiome. Mice were given 2% DSS in drinking water for 5 days, followed by 2 days of regular drinking water. Over the 7 days, mice were dosed daily with either high CBG hemp extract or matched vehicle control. Daily treatment with high CBG hemp extract dramatically reduces the severity of disease at the histological and organismal levels as measured by decreased disease activity index, increased colon length, and decreases in percent colon tissue damage. 16S rRNA gene sequencing of the fecal microbiota reveals high CBG hemp extract treatment results in alterations in the microbiota, that may be beneficial for colitis. Finally, using metabolomic analysis of fecal pellets, we find that mice treated with high CBG hemp extract have a normalization of several metabolic pathways, including those involved in inflammation. Taken together these data suggest that high CBG hemp extracts may offer a novel treatment option for patients. Significance Statement Using the DSS model of colitis, we show that treatment with high CBG hemp extract reduces the severity of symptoms associated with colitis. Additionally, we show that treatment modulates both the fecal microbiota and metabolome with potential functional significance.

Dopamine-induced pruning in monocyte-derived-neuronal-like cells (MDNCs) from patients with schizophrenia.

The long lapse between the presumptive origin of schizophrenia (SCZ) during early development and its diagnosis in late adolescence has hindered the study of crucial neurodevelopmental processes directly in living patients. Dopamine, a neurotransmitter consistently associated with the pathophysiology of SCZ, participates in several aspects of brain development including pruning of neuronal extensions. Excessive pruning is considered the cause of the most consistent finding in SCZ, namely decreased brain volume. It is therefore possible that patients with SCZ carry an increased susceptibility to dopamine's pruning effects and that this susceptibility would be more obvious in the early stages of neuronal development when dopamine pruning effects appear to be more prominent. Obtaining developing neurons from living patients is not feasible. Instead, we used Monocyte-Derived-Neuronal-like Cells (MDNCs) as these cells can be generated in only 20 days and deliver reproducible results. In this study, we expanded the number of individuals in whom we tested the reproducibility of MDNCs. We also deepened the characterization of MDNCs by comparing its neurostructure to that of human developing neurons. Moreover, we studied MDNCs from 12 controls and 13 patients with SCZ. Patients' cells differentiate more efficiently, extend longer secondary neurites and grow more primary neurites. In addition, MDNCs from medicated patients expresses less D1R and prune more primary neurites when exposed to dopamine. Haloperidol did not influence our results but the role of other antipsychotics was not examined and thus, needs to be considered as a confounder.

Optimization of Neurite Tracing and Further Characterization of Human Monocyte-Derived-Neuronal-like Cells.

Deficits in neuronal structure are consistently associated with neurodevelopmental illnesses such as autism and schizophrenia. Nonetheless, the inability to access neurons from clinical patients has limited the study of early neurostructural changes directly in patients' cells. This obstacle has been circumvented by differentiating stem cells into neurons, although the most used methodologies are time consuming. Therefore, we recently developed a relatively rapid (~20 days) protocol for transdifferentiating human circulating monocytes into neuronal-like cells. These monocyte-derived-neuronal-like cells (MDNCs) express several genes and proteins considered neuronal markers, such as MAP-2 and PSD-95. In addition, these cells conduct electrical activity. We have also previously shown that the structure of MDNCs is comparable with that of human developing neurons (HDNs) after 5 days in culture. Moreover, the neurostructure of MDNCs responds similarly to that of HDNs when exposed to colchicine and dopamine. In this manuscript, we expanded our characterization of MDNCs to include the expression of 12 neuronal genes, including tau. Following, we compared three different tracing approaches (two semi-automated and one automated) that enable tracing using photographs of live cells. This comparison is imperative for determining which neurite tracing method is more efficient in extracting neurostructural data from MDNCs and thus allowing researchers to take advantage of the faster yield provided by these neuronal-like cells. Surprisingly, it was one of the semi-automated methods that was the fastest, consisting of tracing only the longest primary and the longest secondary neurite. This tracing technique also detected more structural deficits. The only automated method tested, Volocity, detected MDNCs but failed to trace the entire neuritic length. Other advantages and disadvantages of the three tracing approaches are also presented and discussed.

Vitamin D regulation of the immune system and its implications for COVID-19: A mini review.

The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is at the origin of the current pandemic, predominantly manifests with severe respiratory symptoms and a heightened immune response. One characteristic of SARS-CoV-2 is its capacity to induce cytokine storm leading to acute respiratory distress syndrome. Consequently, agents with the ability to regulate the immune response, such as vitamin D, could become tools either for the prevention or the attenuation of the most severe consequences of the coronavirus disease 2019 (COVID-19). Vitamin D has shown antimicrobial as well as anti-inflammatory properties. While SARS-CoV-2 promotes the release of proinflammatory cytokines, vitamin D attenuates the release of at least some of these same molecules. Inflammatory cytokines have been associated with the clinical phenomena of COVID-19 and in particular with its most dangerous complications. Therefore, the goals of this article are as follows: first, present the numerous roles vitamin D plays in modulating the immune response; second, gather data currently available on COVID-19 clinical presentation and its relation to cytokines and similar molecules; third, expose what it is known about how coronaviruses elicit an inflammatory reaction; and fourth, discuss the potential contribution of vitamin D in reducing the risk and severity of COVID-19.

Quetiapine and Wolff-Parkinson-White Syndrome.

Quetiapine is occasionally associated with cardiovascular adverse effects such as QTc prolongation. QTc prolongation is a side effect that requires monitoring in order to avoid more serious cardiac complications. One particular understudied area is the potential for antipsychotics to elicit electroconduction abnormalities in patients with Wolff-Parkinson-White (WPW) Syndrome. In the present report, we describe a case of quetiapine overdose in a patient with WPW.