Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Potential Probiotic or Trigger of Gut Inflammation - The Janus-Faced Nature of Cannabidiol-Rich Cannabis Extract.

ABSTRACT: Cannabidiol (CBD) is the major non-psychotropic phytocannabinoid present in Cannabis sativa. In 2018, Congress designated certain C. sativa plant material as "hemp," thus removing it from the DEA's list of controlled substances. As a result, CBD-containing hemp extracts and other CBD products are now widely available and heavily marketed, yet their FDA regulatory status is still hotly debated. The goal of this study was to investigate the effects of a cannabidiol-rich cannabis extract (CRCE) on the gut microbiome and associated histomorphological and molecular changes in the mouse gut mucosa. Male C57BL6/J mice were gavaged with either 0, 61.5, 184.5, or 615 mg/kg/bw of CRCE in sesame oil for 2 weeks (Mon-Fri). Substantial CRCE-induced increases in the relative abundance of A. muciniphila, a bacterial species currently accepted as probiotic, was observed in fecal samples at all doses. This was paralleled by decreases in the relative abundance of other gut bacterial species. Coincident with the observed changes in gut ecology were multiple pro-inflammatory responses, including increased expression of cytokines and chemokines-Il1ß, Cxcl1, and Cxcl2 in the colon tissue. Furthermore, dramatic increases in the relative abundance of A. muciniphila significantly decreased expression of Muc2-a gene intimately associated with gut integrity. Taken together, these findings raise concerns about the safety of long-term CBD usage and underline the need for additional well-designed studies into its tolerability and efficacy.

SUBMITTER: Skinner CM

PROVIDER: S-EPMC7470626 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model.

Project description:The goal of this study was to investigate Cannabidiol (CBD) hepatotoxicity in 8-week-old male B6C3F1 mice. Animals were gavaged with either 0, 246, 738, or 2460 mg/kg of CBD (acute toxicity, 24 h) or with daily doses of 0, 61.5, 184.5, or 615 mg/kg for 10 days (sub-acute toxicity). These doses were the allometrically scaled mouse equivalent doses (MED) of the maximum recommended human maintenance dose of CBD in EPIDIOLEX® (20 mg/kg). In the acute study, significant increases in liver-to-body weight (LBW) ratios, plasma ALT, AST, and total bilirubin were observed for the 2460 mg/kg dose. In the sub-acute study, 75% of mice gavaged with 615 mg/kg developed a moribund condition between days three and four. As in the acute phase, 615 mg/kg CBD increased LBW ratios, ALT, AST, and total bilirubin. Hepatotoxicity gene expression arrays revealed that CBD differentially regulated more than 50 genes, many of which were linked to oxidative stress responses, lipid metabolism pathways and drug metabolizing enzymes. In conclusion, CBD exhibited clear signs of hepatotoxicity, possibly of a cholestatic nature. The involvement of numerous pathways associated with lipid and xenobiotic metabolism raises serious concerns about potential drug interactions as well as the safety of CBD.

| S-EPMC6539990 | biostudies-other

Janus-faced nature of light in the cold acclimation processes of maize

Project description:Earlier findings indicated that light plays a critical role in the development of frost tolerance in winter cereals. However, the exact mechanism is still poorly understood. In the present work the effects of light during the cold acclimation period were studied in chilling-sensitive maize plants. The results show that although exposure to relatively high light intensities during cold acclimation at 15 °C causes various stress symptoms, it enhances the effectiveness of acclimation to chilling conditions (5 °C in the light). Interestingly, certain stress responses were light-dependent not only in the leaves, but also in the roots. A microarray study was also conducted to achieve a better understanding of the interaction of low temperature and light intensity during the cold hardening period. Numerous genes significantly differentially expressed were observed in almost all assimilation and metabolic pathways. Acclimation at moderately low temperature and low light intensity reduced the level of soluble sugars, while chilling increased it. Greater accumulation during hardening was detected at relatively high light intensity. It seems that the photoinhibition induced by low temperature is a necessary evil for cold acclimation processes in plants.

2020-12-31 | GSE107913 | GEO

Safety and Molecular-Toxicological Implications of Cannabidiol-Rich Cannabis Extract and Methylsulfonylmethane Co-Administration.

Project description:Cannabidiol (CBD) is a biologically active, non-psychotropic component of Cannabis sativa whose popularity has grown exponentially in recent years. Besides a wealth of potential health benefits, ingestion of CBD poses risks for a number of side effects, of which hepatotoxicity and CBD/herb-drug interactions are of particular concern. Here, we investigated the interaction potential between the cannabidiol-rich cannabis extract (CRCE) and methylsulfonylmethane (MSM), a popular dietary supplement, in the mouse model. For this purpose, 8-week-old male C57BL6/J mice received MSM-containing water (80 mg/100 mL) ad libitum for 17 days. During the last three days of treatment, mice received three doses of CRCE administered in sesame oil via oral gavage (123 mg/kg/day). Administration of MSM alone did not result in any evidence of liver toxicity and did not induce expression of mouse cytochrome P450 (CYP) enzymes. Administration of CRCE did produce significant (p < 0.05) increases in Cyp1a2, Cyp2b10, Cyp2c29, Cyp3a4, Cyp3a11, Cyp2c65, and Cyp2c66 messenger RNA, however, this effect was not amplified by MSM/CRCE co-treatment. Similarly, no evidence of liver toxicity was observed in MSM/CRCE dosed mice. In conclusion, short-term MSM/CRCE co-administration did not demonstrate any evidence of hepatotoxicity in the mouse model.

| S-EPMC7656295 | biostudies-literature

Janus-Faced Nature of Light in the Cold Acclimation Processes of Maize.

Project description:Exposure of plants to low temperature in the light may induce photoinhibitory stress symptoms, including oxidative damage. However, it is also known that light is a critical factor for the development of frost hardiness in cold tolerant plants. In the present work the effects of light during the cold acclimation period were studied in chilling-sensitive maize plants. Before exposure to chilling temperature at 5°C, plants were cold acclimated at non-lethal temperature (15°C) under different light conditions. Although exposure to relatively high light intensities during cold acclimation caused various stress symptoms, it also enhanced the effectiveness of acclimation processes to a subsequent severe cold stress. It seems that the photoinhibition induced by low temperature is a necessary evil for cold acclimation processes in plants. Greater accumulations of soluble sugars were also detected during hardening at relatively high light intensity. Certain stress responses were light-dependent not only in the leaves, but also in the roots. The comparison of the gene expression profiles based on a microarray study demonstrated that the light intensity is at least as important a factor as the temperature during the cold acclimation period. Differentially expressed genes were mainly involved in most of assimilation and metabolic pathways, namely photosynthetic light capture via the modification of chlorophyll biosynthesis and the dark reactions, carboxylic acid metabolism, cellular amino acid, porphyrin or glutathione metabolic processes, ribosome biogenesis and translation. Results revealed complex regulation mechanisms and interactions between cold and light signalling processes.

| S-EPMC6018404 | biostudies-literature

The Janus-faced nature of the C(2)B domain is fundamental for synaptotagmin-1 function.

Project description:Synaptotagmin-1 functions as a Ca2+ sensor in neurotransmitter release and was proposed to act on both the synaptic vesicle and plasma membranes through interactions involving the Ca2+ binding top loops of its C(2) domains and the Ca2+-independent bottom face of the C(2)B domain. However, the functional importance of the C(2)B domain bottom face is unclear. We now show that mutating two conserved arginine residues at the C(2)B domain bottom face practically abolishes synchronous release in hippocampal neurons. Reconstitution experiments reveal that Ca2+-synaptotagmin-1 can dramatically stimulate the rate of SNARE-dependent lipid mixing, and that the two-arginine mutation strongly impairs this activity. These results demonstrate that synaptotagmin-1 function depends crucially on the bottom face of the C(2)B domain and strongly support the notion that synaptotagmin-1 triggers membrane fusion and neurotransmitter release by bringing the vesicle and plasma membranes together, much like the SNAREs do but in a Ca2+-dependent manner.

| S-EPMC2587052 | biostudies-literature

Hair Regrowth with Cannabidiol (CBD)-rich Hemp Extract - A Case Series.

Project description:Androgenetic alopecia (AGA) is the most common cause of hair loss. Several FDA approved medications are available but offer limited results. Studies have shown that the endocannabinoid system (ECS) is a key player in hair follicle cell growth. The ECS cannabinoid type one (CB1) receptors are well expressed in the hair follicle cells. Cannabidiol CBD is a negative allosteric modulator of the CB1 receptor and has been shown to result in hair shaft elongation. In addition, the hair follicle cycle phases are controlled by the ECS vanilloid receptor-1 (TRPV1). CBD has also been shown to increase Wnt signaling pathways that are involved in the differentiation of dermal progenitor cells into new hair follicles and maintaining the anagen phase of the hair cycle. The effects of CBD on hair growth are dose dependent and higher doses may result in premature entry into the catagen phase via a receptor known as vanilloid receptor-4 (TRPV4). Topical application of CBD reaches hair follicles where it is a CB1 negative modulator, and TRPV1, and TRPV4 agonist. A study was done of 35 subjects with AGA using a once daily topical hemp oil formulation, averaging about 3-4 mg per day of CBD and minimal amounts of other cannabinoids for six months. A hair count of the greatest area of alopecia was carried out before treatment and again after six months. The results revealed that men did slightly better than women, and the vertex area did better than the temporal areas. On average there was statistically significant 93.5% increase in hair after 6 months. All subjects had some regrowth. There were no reported adverse effects. Since the CBD works through novel mechanisms different from finasteride and minoxidil it can be used in conjunction with these current drugs and would be expected to have synergistic effects.

| S-EPMC10212262 | biostudies-literature

Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration.

Project description:The goal of this study was to investigate the potential for a cannabidiol-rich cannabis extract (CRCE) to interact with the most common over-the-counter drug and the major known cause of drug-induced liver injury-acetaminophen (APAP)-in aged female CD-1 mice. Gavaging mice with 116 mg/kg of cannabidiol (CBD) [mouse equivalent dose (MED) of 10 mg/kg of CBD] in CRCE delivered with sesame oil for three consecutive days followed by intraperitoneally (i.p.) acetaminophen (APAP) administration (400 mg/kg) on day 4 resulted in overt toxicity with 37.5% mortality. No mortality was observed in mice treated with 290 mg/kg of CBD+APAP (MED of 25 mg/kg of CBD) or APAP alone. Following CRCE/APAP co-administration, microscopic examination revealed a sinusoidal obstruction syndrome-like liver injury-the severity of which correlated with the degree of alterations in physiological and clinical biochemistry end points. Mechanistically, glutathione depletion and oxidative stress were observed between the APAP-only and co-administration groups, but co-administration resulted in much greater activation of c-Jun N-terminal kinase (JNK). Strikingly, these effects were not observed in mice gavaged with 290 mg/kg CBD in CRCE followed by APAP administration. These findings highlight the potential for CBD/drug interactions, and reveal an interesting paradoxical effect of CBD/APAP-induced hepatotoxicity.

| S-EPMC6630875 | biostudies-other

Interleukin 17A: a Janus-faced regulator of osteoporosis.

Project description:Interleukin (IL)-17A is a well-described mediator of bone resorption in inflammatory diseases, and postmenopausal osteoporosis is associated with increased serum levels of IL-17A. Ovariectomy (OVX) can be used as a model to study bone loss induced by estrogen deficiency and the role of IL-17A in osteoporosis development has previously been investigated using various methods to inhibit IL-17A signaling in this model. However, the studies show opposing results. While some publications reported IL-17A as a mediator of OVX-induced osteoporosis, others found a bone-protective role for IL-17 receptor signaling. In this study, we provide an explanation for the discrepancies in previous literature and show for the first time that loss of IL-17A has differential effects on OVX-induced osteoporosis; with IL-17A being important for cortical but not trabecular bone loss. Interestingly, the decrease in trabecular bone after OVX in IL-17A knock-out mice, was accompanied by increased adipogenesis depicted by elevated leptin levels. Additionally, the bone marrow adipose tissue expanded, and the bone-turnover decreased in ovariectomized mice lacking IL-17A compared to ovariectomized WT mice. Our results increase the understanding of how IL-17A signaling influences bone remodeling in the different bone compartments, which is of importance for the development of new treatments of post-menopausal osteoporosis.

| S-EPMC7105470 | biostudies-literature

"Janus-Faced" α-Synuclein: Role in Parkinson's Disease.

Project description:Parkinson's disease (PD) is a pathological condition characterized by the aggregation and the resultant presence of intraneuronal inclusions termed Lewy bodies (LBs) and Lewy neurites which are mainly composed of fibrillar α-synuclein (α-syn) protein. Pathogenic aggregation of α-syn is identified as the major cause of LBs deposition. Several mutations in α-syn showing varied aggregation kinetics in comparison to the wild type (WT) α-syn are reported in PD (A30P, E46K, H 50Q, G51D, A53E, and A53T). Also, the cell-to-cell spread of pathological α-syn plays a significant role in PD development. Interestingly, it has also been suggested that the pathology of PD may begin in the gastrointestinal tract and spread via the vagus nerve (VN) to brain proposing the gut-brain axis of α-syn pathology in PD. Despite multiple efforts, the behavior and functions of this protein in normal and pathological states (specifically in PD) is far from understood. Furthermore, the etiological factors responsible for triggering aggregation of this protein remain elusive. This review is an attempt to collate and present latest information on α-syn in relation to its structure, biochemistry and biophysics of aggregation in PD. Current advances in therapeutic efforts toward clearing the pathogenic α-syn via autophagy/lysosomal flux are also reviewed and reported.

| S-EPMC8194081 | biostudies-literature