Are CBD Gummies Bad For Your Liver

CBDISTILLERY

Buy CBD Oil Online

Alcohol abuse and high fat diet induced liver diseases have been the most prevalent chronic liver diseases and the leading reasons for liver transplantation around the world. Cannabidiol (CBD) is a botanical component extracted from marijuana plants without psychoactive impact. In our previous reports, CBD can prevent fatty liver induced by Lieber DeCarlie ethanol diet or non-alcoholic fatty liver disease (NAFLD) induced by high fat high cholesterol diet. The current study is a further study on whether CBD can alleviate liver injuries induced by ethanol plus high fat high cholesterol diet (EHFD), which is a model simulating heavy alcohol drinkers in a western diet. A mice liver injury model induced by EHFD for 8 weeks was applied to explore the protective properties of CBD and the underlying mechanisms. We found that CBD prevented liver steatosis as well as oxidative stress induced by EHFD. CBD treatment inhibited macrophage recruitment, and suppressed activation of NFκB-NLRP3-pyroptosis pathway in mouse livers. The hepatoprotective property of CBD in the current model might be a result of inhibition of inflammation via alleviating activation of hepatic NFκB-NLRP3 inflammasome-pyroptosis pathway by CBD. While CBD oil is generally safe, it is important to be aware of the potential risks involved before you start using it. This includes the possibility of liver damage. In this article, we'll take a look at the evidence surrounding CBD and liver damage to see if you should be concerned. What is CBD? CBD is short for Cann

CBD Alleviates Liver Injuries in Alcoholics With High-Fat High-Cholesterol Diet Through Regulating NLRP3 Inflammasome–Pyroptosis Pathway

Alcohol abuse and high-fat diet–induced liver diseases have been the most prevalent chronic liver diseases and the leading reasons for liver transplantation around the world. Cannabidiol (CBD) is a botanical component extracted from marijuana plants without psychoactive impact. In our previous reports, we found that CBD can prevent fatty liver induced by Lieber–DeCarli ethanol diet or non-alcoholic fatty liver disease (NAFLD) induced by high-fat high-cholesterol diet. The current work is a further study on whether CBD can alleviate liver injuries induced by ethanol plus high-fat high-cholesterol diet (EHFD), which is a model simulating heavy alcohol drinkers in a Western diet. A mice liver injury model induced by EHFD for 8 weeks was applied to explore the protective properties of CBD and the underlying mechanisms. We found that CBD prevented liver steatosis and oxidative stress induced by EHFD. CBD treatment inhibited macrophage recruitment and suppressed activation of NFκB–NLRP3–pyroptosis pathway in mice livers. The hepatoprotective property of CBD in the current model might be a result of inhibition of inflammation via alleviating activation of the hepatic NFκB–NLRP3 inflammasome–pyroptosis pathway by CBD.

Introduction

Prolonged heavy consumption of alcohol-induced liver injuries accounts for the increasing morbidity and mortality rates worldwide (Xu et al., 2017). These liver injuries are characterized by a spectrum of progressing liver disorders, including simple fatty liver, alcoholic hepatitis, cirrhosis, and hepatocellular carcinoma (Seitz et al., 2018). Individuals abusing alcohol are usually accompanied with a superfluous calorie intake which will raise their predisposition of developing a metabolic disorder such as obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM) (Boyle et al., 2018). It has been recognized for many years that chronic heavy alcohol drinking can have synergistic or exacerbating effects on obesity and metabolic syndrome, which can further promote the formation of fatty Rinella (2015a) liver and aggravate the progression of ALD (Boyle et al., 2018) (Rinella, 2015b). Haein et al. proved that significant hepatic damage can be caused by alcohol administration for four weeks with increased hepatic lipid droplets and inflammatory cytokine levels and can be aggravated with the combination of high-fat diet (Kim et al., 2016). In the present study, we applied chronic administration of alcohol with a high-fat high-cholesterol diet (EHFD) to induce hepatic injury in mice.

Inflammation plays an important role in the formation and progress of liver damage induced either by alcohol or high-fat diet. Pyroptosis is an inflammatory process of caspase-1–dependent programmed cell death. In pyroptosis, the inflammasome and some other signals are activators of caspases. In general, pyroptosis starts with inflammasome formation recognizing various exogenous and endogenous signals, including LPS and ATP, and caspase-1 is subsequently activated. The activation of caspase-1 by the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome leads to the cleavage of pro-inflammatory cytokine interleukin-1 beta (IL-1β) and pro-interleukin 18 (IL-18) and the production of mature IL-1β and IL-18. In addition, activated caspase-1 cleaves the pyroptotic substrate gasdermin D (GSDMD) and forms the membrane pores and induces pyroptosis, allowing the release of IL-1β and IL-18.

In canonical pyroptosis, inflammasome formation is an initiation step for pyroptosis activation. The inflammasome is an inflammatory signal platform, which can react with exogenous and endogenous signals and initiate a series of inflammatory responses (Fabio et al., 2002). The inflammasome is a cytoplasmic complex, mainly composed of three different functional proteins: sensor proteins, including a nucleotide-binding oligomerization domain (NOD)–like receptors (NLRs) family members; the adapter protein comprised apoptosis-associated speck-like protein containing a casp recruitment domain (ASC)— the effective protein pro-caspase-1 (Fabio et al., 2002; Benetti et al., 2013). Among the inflammasomes, studies have highlighted the importance of the NLRP3 inflammasome in many inflammatory disorders (Benetti et al., 2013), such as ALD, obesity (Mastrocola et al., 2018), type 2 diabetes (Luo et al., 2017), non-alcoholic fatty liver disease (NAFLD) (Wan et al., 2016; Cabrera et al., 2017), and metabolic syndrome (Mastrocola et al., 2018). The NLRP3 inflammasome can be activated by endogenous or exogenous factors, including pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), pore-forming toxins, and environmental irritants (Fabio et al., 2002). Nuclear factor κB (NF-κB) has been demonstrated as one of key factors activating the NLRP3 inflammasome. Upon activation of the NLRP3 inflammasome, caspase-1 is activated. Activated caspase-1 would cleave pro-IL-1β into mature IL-1β, resulting in release of IL-1β, inflammation, and cell and tissue damage (Fabio et al., 2002). In addition, activated caspase-1 cleaves GSDMD and forms membrane pores, which is a key step for pyroptosis, allowing the release of IL-1β and IL-18.

Excessive activation of inflammatory caspases is implicated in the pathogenesis of alcoholic liver disease and NASH, and pyroptosis is the dominant response following this activation (Jorgensen and Miao, 2015). Heo et al. proved that pyroptosis occurs in hepatocytes with alcohol exposure as NLRP3, ASC, and caspase-1 were all upregulated with ethanol (Heo et al., 2019). Numerous studies have shown that pyroptosis is an inflammatory link between simple steatosis and NASH, since no NLRP3 activation was observed in simple steatosis without inflammation, while NLRP3 activation in NASH has been shown in both human and animal models (Csak et al., 2011; Beier and Banales, 2018). Moreover, researchers had proved that the pyroptosis-inducing fragment GSDMD expression was higher in NASH and that IL-1β released following pyroptosis is the driver of liver inflammation and fibrosis (Tilg and Moschen, 2011; Shi et al., 2015).

Cannabidiol (CBD), a non-psychomimetic compound extracted from Cannabis sativa, exerts a broad range of pharmacological properties, including cardiac and neural protection, antioxidant and anti-inflammatory capabilities, and anti-epileptic potential (Yang et al., 2014; Wang et al., 2017; Huang et al., 2019). Although CBD can cross the blood–brain barrier, it does not cause psychoactive effects that lack abuse potential. CBD has been shown to reduce the inflammation in cultured human sebocytes and human skin organ culture through coupling to A2A adenosine receptor–dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of NF-κB signaling (Oláh et al., 2014). Moreover, the intervention of CBD delayed the onset of type 1 diabetes in non-obese diabetic mice and alleviated pancreas inflammation (Lehmann et al., 2016). It has also been shown that the administration of CBD targeted NF-κB and NLRP3 inflammasome pathways in macrophages, which could be a novel treatment for NASH (Mridha et al., 2017). In addition, CBD treatment suppressed hepatic lipid accumulation and attenuated oxidative stress and inflammatory response induced by excess energy diet Huang et al. (2019) or alcohol intake (Wang et al., 2017). Recent studies have shown that CBD was able to reduce accumulation of intracellular lipid levels (Silvestri et al., 2015) and cell death (Mukhopadhyay et al., 2011) in dose- and time-dependent manners. It is still elusive whether CBD can protect liver injury induced by EHFD, and the related mechanisms are unclear. Here, we aim to explore the potentiality of CBD for mitigating liver inflammation induced by EHFD, as well as the mechanism therein, focusing on the NLRP3 inflammasome–pyroptosis pathway in macrophages.

Materials and Methods

Reagents

Cannabidiol (CBD) was from Tocris Bioscience (Ellisville, MO, United States, 1570/10), with purity ≥98% (HPLC). TRIzol was supplied by Invitrogen (Carlsbad, CA, United States). The PrimeScript RT Reagent Kit with a gDNA eraser and SYBR Premix Ex TaqII kit were from TaKaRa (Tokyo, Japan). Lysis buffer for Western blot and a BCA protein assay kit were purchased from Beyotime Biotechnology Company (Shanghai, China). Anti-pIκBα (9246s), anti-IκBα (4812s), anti-pNF-κB p65 (3033s), anti-NF-κB p65 (8242s), anti-ASC (#67824), and anti-IL-1β (#12242) were from Cell Signaling Technology. Anti-NLRP3 (ab214185) and anti-tubulin (ab6160) were obtained from Abcam. Anti–pro-caspase-1 (22915-1-AP) and anti-GSDMD (20770-1-AP) were obtained from Proteintech Group Inc. (United States). Anti-GAPDH (sc25778), anti–caspase-1 p20 (sc25778), and all secondary antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, United States).

Animal Experimental Protocol

Six-week-old male C57B/6J mice were supplied by the Sun Yat-sen University Animal Center (Guangzhou, China). Animal experiments were approved by the Animal Experimentation Ethics Committee of Sun Yat-sen University, complied with the ARRIVE guidelines and the National Institutes of Health Guide for the Care and Use of Laboratory Animals. All mice were kept at a specific pathogen‐free environment (temperature 20–22°C, humidity 60%) with 12-hour light/dark cycle and free access to food and water. After two weeks of acclimatization, the mice were randomly assigned to the following three groups: 1) the control group, received a standard chow diet (5% fat w/w); 2) the EHFD group, received a high-fat high-cholesterol diet (containing 17% fat and supplemented with 1.25% cholesterol and 0.5% cholate) which was obtained from Trophic Animal Feed High-tech Co. Ltd. (China) Gäbele et al. (2011), with ad libitum access to alcohol in drinking water with increasing concentrations of alcohol (1% v/v of alcohol for the first 2 days, 2% from day 3 to day 7, 4% for the second week, and 5% for another 6 weeks); and 3) the EHFD + CBD group, on the basis of EHFD group, mice were gavaged with 5 mg/kg BW CBD solution per day for 8 weeks. The control and EHFD mice were given saline at equivalent volumes. The animal experiment protocol is shown in Figure 1A. The mice were euthanized at the age of 16 weeks after they were fasted for 16 h, and the serum and liver tissue were harvested for subsequent measurement.

FIGURE 1. CBD treatment ameliorated steatohepatitis induced by EHFD diet. Mice were fed ethanol plus high-fat high cholesterol diet for 8 weeks with or without CBD treatment. Control mice were fed a standard chow diet. The animal experiment protocol (A). Representative H&E staining of liver sections (magnification ×200) (B). Levels of hepatic TG (C) and TC (D). Levels of serum ALT (E) and AST (F). Values represent mean ± SEM (n = 6–8/group). *p < 0.05 vs the control group; #p < 0.05 vs the EHFD group.

Biochemical Analysis

The serum was collected after 3000×g centrifugation at 4°C for 15 min. Levels of serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), hepatic triglyceride (TG), and hepatic total cholesterol (TC) were determined by corresponding kits (Jiancheng Biotech, Nanjing, China) according to the manufacturer protocol. Hepatic malondialdehyde (MDA) levels, glutathione/glutathione disulfide (GSH/GSSG) levels, and activity of superoxide dismutase (SOD) were determined by using ELISA kits (Beyotime, Shanghai, China). The values were normalized by protein content.

Histology and Immunohistochemical Analysis

Western Blot Analysis

The proteins extracted from the liver tissues were analyzed by Western blot. The liver tissues were homogenized using RIPA (radioimmunoprecipitation assay) lysis buffer supplemented with protease and phosphatase inhibitors. The proteins were separated by 8–12% SDS-PAGE, followed by transferring to a 0.22/0.45-mm polyvinylidene difluoride (PVDF) membrane (Millipore, Billerica, MA, United States). The membranes were pre-blocked with 5% (w/v) fat-free milk in phosphate-buffered saline containing 0.05% (v/v) Tween-20 (TBST). The membrane was incubated at 4°C overnight with specific primary antibodies and subsequently incubated with HRP-conjugated secondary antibodies at room temperature for 1 h. The ECL Reagent Kit (Thermo) was used to determine signals. Primary antibodies included anti-pIκBα, anti-IκBα, anti-NF-κB p65, anti-pNF-κB p65, anti-NLRP3, anti-ASC, anti–pro-caspase-1, anti–caspase-1 p20, anti-GSDMD, anti-IL-1β, anti-GAPDH, and anti-tubulin. The band intensities were analyzed by ImageJ software.

Quantitative Real-Time Polymerase Chain Reaction

Total RNAs were extracted from livers with TRIzol reagent and reverse-transcribed into cDNA with a PrimeScript RT Reagent Kit. Gene expression was determined by quantitative real-time PCR with an SYBR Premix Ex Taq II kit and signaling detected by a Vii7 system (ABI, Carlsbad, CA, United States). Expression of each target gene was normalized to the internal standard (β-actin) by using the 2 −ΔΔCt comparative method. Primer sequences are listed in Table 1.

TABLE 1. Primer sequences for quantitative real-time polymerase chain reaction.

Statistical Analysis

All statistical analyses were performed with SPSS 20.0, and a p value < 0.05 was considered statistically significant. Data were expressed as means ± SE analyzed by Student’s t-test (for two groups) or one-way ANOVA (for more than two groups), followed by the Bonferroni test.

Result

CBD Treatment Ameliorated Steatohepatitis Induced by EHFD Diet

As shown in Figure 1B, EHFD diet resulted in marked hepatocellular lipid accumulation with obvious inflammatory cell infiltration in mice liver as compared with those in control, while CBD treatment markedly decreased lipid droplets and inflammatory lesions induced by EHFD in H&E-stained liver sections. Correspondingly, we found that the levels of TG and TC in the liver increased in the EHFD group (Figures 1C, D), with significantly increased serum ALT and AST levels (Figures 1E, F), indicating the development of steatohepatitis and the damage of liver cells in EHFD treatment. CBD treatment significantly inhibited hepatic steatohepatitis and liver injury induced by EHFD diet.

CBD Treatment Alleviated Oxidative Stress Induced by EHFD Diet

Excess of oxidative stress contributes to cellular injury and the development of non-alcoholic and alcoholic liver disease. To evaluate the effect of CBD on oxidative stress, we measured the activity of enzymes that maintain redox homeostasis and the level of lipid peroxidation product in mice liver. Figures 2A, B show that the mice in the EHFD group displayed significantly increased contents of MDA and a decreased ratio of GSH/GSSG, whereas these alterations were inhibited in the presence of CBD. Moreover, EHFD decreased hepatic activity of SOD, which was slightly increased by CBD treatment, with no statistical significance compared to the EHFD group (Figure 2C).

FIGURE 2. CBD treatment alleviated oxidative stress induced by EHFD diet. Mice were fed ethanol plus high-fat high cholesterol diet for 8 weeks with or without CBD treatment. Control mice were fed a standard chow diet. Levels of hepatic MDA (A). The ratio of hepatic GSH/GSSG (B). Activity of hepatic SOD (C). Values represent mean ± SEM (n = 6–8/group). *p < 0.05 vs the control group; #p < 0.05 vs the EHFD group.

Inflammation Induced by EHFD Diet Was Ameliorated by CBD Treatment

The H&E-stained liver sections revealed that CBD treatment decreased hepatic inflammation in EHFD mice. To further verify the anti-inflammatory effect of CBD, we assessed the expression of CD68 (macrophage marker) in mice liver. Immunohistochemistry staining of liver sections indicated that number of CD68-positive cells was increased in the EHFD group, suggesting an increased inflammatory cell infiltration. The expression of CD68 was blunted in the CBD group (Figure 3A). Consistently, gene expressions of the inflammatory markers such as F4/80, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α) were increased in the EHFD group, while these gene expressions were significantly reduced with CBD treatment (Figures 3B–E). These results indicated that administration of CBD alleviated the inflammatory response induced by EHFD.

See also  CBD Oil For Knee Pain After Surgery

FIGURE 3. Inflammation induced by EHFD diet was ameliorated by CBD treatment. Mice were fed ethanol plus high-fat high cholesterol diet for 8 weeks with or without CBD treatment. Control mice were fed standard chow diet. Immunohistochemistry staining was performed to determine CD68 + macrophages (magnification ×200 and ×400) (A). The mRNA expressions of F4/80 (B), IL-1β (C), MCP-1 (D), and TNF-α (E) were analyzed by qPCR. Values represent mean ± SEM (n = 6–8/group). *p < 0.05 vs the control group; #p < 0.05 vs the EHFD group.

CBD Treatment Inhibited the Activation of NF-κB Pathway Induced by EHFD Treatment

NF-κB is a key transcription factor that controls the expression of pro-inflammatory genes. To determine the possible involvement of the NF-κB pathway in the anti-inflammatory effect of CBD, we examined IκBα and NF-κB in the liver samples by Western blot. As shown in Figure 4, IkBa was decreased due to its phosphorylation in the EHFD group, EHFD treatment increased the expressions of phosphorylated IκBα and NF-κB, and the ratios of pIκBα/IκBα and pNF-κB/NF-κB increased, indicating the activation of the NF-κB pathway by EHFD. CBD treatment decreased the expressions of pIκBα, pNF-κB, the ratios of pIκBα/IκBα, and pNF-κB/NF-κB, showing the inhibition effect of CBD on NF-κB activation, suggesting the effect of CBD on EHFD-induced inflammation is associated with the activation of the NF-κB pathway.

FIGURE 4. CBD treatment inhibited NF-κB pathway activation induced by the EHFD diet. Mice were fed ethanol plus high-fat high-cholesterol diet for 8 weeks with or without CBD treatment. Control mice were fed a standard chow diet. Western blot analyses of pIκBα, IκBα, pNF-κB p65, and NF-κB p65 (A). Quantification of expressions of IκBα, pIκBα, and pNF-κB p65 (B). Values represent mean ± SEM (n = 6–8/group). *p < 0.05 vs the control group; #p < 0.05 vs the EHFD group.

CBD Treatment Suppressed NLRP3 Inflammasome Activation and Pyroptosis in EHFD-Fed Mice

NLRP3 inflammasome activation may lead to GSDMD-driven pyroptosis, which plays a key role in the occurrence and development of liver diseases (Guo et al., 2019). We explored whether CBD could attenuate NLRP3 inflammasome activation and the subsequent pyroptosis in livers. As shown in Figures 5A, B, EHFD diet significantly increased NLRP3, ASC, and caspase-1 p20 protein levels, which indicates NLRP3 inflammasome activation, while their expressions were significantly decreased by CBD treatment.

FIGURE 5. CBD treatment suppressed NLRP3 inflammasome activation and pyroptosis in EHFD-fed mice. Mice were fed ethanol plus high-fat high-cholesterol diet for 8 weeks with or without CBD treatment. Control mice were fed a standard chow diet. Western blot analyses of NLRP3, ASC, pro-caspase-1, and caspase-1 p20 (A). Quantification of expressions of NLRP3, ASC, and caspase-1 p20 (B). Western blot analyses of GSDMD and cleaved GSDMD (C). Quantification of relative expressions of cleaved GSDMD (D). Western blot analyses of IL-1β and pro-IL-1β (E). Quantification of expression of IL-1β (F). *p < 0.05 vs the control group; #p < 0.05 vs the EHFD group.

As certain inflammasomes trigger the inflammatory form of cell death, we then assessed the cleavage of GSDMD, which is the executor of cell pyroptosis. As shown in Figures 5C, D, the expression of cleaved GSDMD in the EHFD group was approximately 1.4 times higher than that in the control group. CBD treatment significantly lowered the protein expression of cleaved GSDMD in livers. Meanwhile, the protein levels of downstream inflammatory cytokine IL-1β were reduced by CBD treatment (Figures 5E, F). Thus, our results suggested a novel mechanism of CBD attenuating liver inflammatory response by inhibiting the NLRP3 inflammasome–pyroptosis pathway.

Discussion

Metabolism-related liver diseases have been severe public health burdens worldwide. The early stage of liver diseases is reversible through alcohol abstinence, nutritional intervention, or medical treatment (Louvet and Mathurin, 2015). Recently, hepatoprotective property of CBD has been reported in several research studies both in the ALD mice model and cell model (Yang et al., 2014; Wang et al., 2017; Huang et al., 2019). In this study, we employed a liver-damaged mouse model induced by EHFD, which was used to imitate the alcoholics with Western dietary pattern (Gäbele et al., 2011). Our results demonstrated that CBD exerted a beneficial effect in preventing liver injury induced by EHFD diet; 1) CBD reduced lipid accumulation, liver injury, and oxidative stress induced by EHFD diet; 2) CBD attenuated inflammation, by suppressing activation of NF-κB and activation of the NLRP3 inflammasome; and 3) CBD inhibited cleaved GSDMD formation induced by EHFD treatment. Herein, our research is the first to have examined the function of CBD, which protected the liver from injury and inflammation induced by EHFD diet, by regulating the NF-κB–NLRP3 inflammasome–pyroptosis pathway.

Oxidative stress plays a key part in the pathogenesis of liver injuries by alcohol or high-fat diet (Xu et al., 2017). Acute or chronic alcohol drinking or high-fat diet may induce oxidative stress by increasing reactive oxygen species (ROS) production or decreasing antioxidant enzyme activities (Wei et al., 2019), resulting in liver injury. Much evidence indicated that CBD can possess antioxidant properties. We have reported previously that CBD can prevent fatty liver induced by alcohol via inhibiting oxidative stress and activating the autophagy pathway (Yang et al., 2014). In line with these reports, we found that CBD lessened EHFD-induced oxidative stress, which was shown by the increasing levels of MDA, the decreasing ratio of GSH/GSSG, and the reduction of the activity of SOD. The increased ratio of GSH/GSSG may contribute to the protection of livers from oxidative stress induced by EHFD. These indicated that part of the hepatoprotective effect of CBD derives from its antioxidative effect.

Chronic alcohol abuse or long-term high-fat diet can lead to augmentation of enteric permeability, hepatocyte injury, and activation of immune cells, resulting in the release of LPS, pro-inflammatory chemokines, and DAMPs (Kawaratani et al., 2017). Consequently, these factors may stimulate the inflammatory response, which is responsible for the progression of liver injuries. Inflammation in the liver has been proven to be a major contributor to the progression of liver disease. Importantly, it has been reported that CBD exerted a noteworthy anti-inflammatory effect in many disorders. Moreover, our laboratory and others previously found that CBD alleviated liver injury of NAFLD by suppressing NF-κB and the NLRP3 inflammasome (Mridha et al., 2017; Huang et al., 2019). In this study, besides inhibiting liver injury, we also found that CBD treatment prominently alleviated the inflammation induced by EHFD shown by counterbalancing the increment of macrophages in the liver induced by EHFD diet. Elevated infiltration of macrophages into the liver is an established pathological alteration of inflammation Zhang et al. (2018), resulting in the release of various cytokines, such as TNF-α, IL-1β, and MCP-1, which could exacerbate liver damage (Xiang et al., 2015). In line with this, we found that CBD treatment actually ameliorated the expression of TNF-α, IL-1β, and MCP-1 in the livers of EHFD-treated mice.

Although these detrimental factors can stimulate inflammatory response through diverse pathways, the most important one of these pathways is characterized by the activation of NF-κB. While these agonists combine with different receptors (Boaru et al., 2015), such as tumor necrosis factor receptor, toll-like receptors (TLRs) (Xiang et al., 2015), IL-1β receptor, and the cytosolic pattern recognition receptor (NOD2), the IκB kinase (IKK) subsequently is catalyzed into an active form, as well as NF-κB (Liu et al., 2017). Unsurprisingly, EHFD feeding caused the activation of IKK and NF-κB. However, CBD visibly inhibited these alterations. Of the NF-κB pathway network, the activation of the NLRP3 inflammasome is a major contributor to chronic liver diseases (Wu et al., 2017). Upgradation of NLRP3 by active NF-κB (signal 1), the so-called priming step, is the first and indispensable process in the activation of the NLRP3 inflammasome (Volt et al., 2016). Followed by the stimulation of signal 2, ACS is recruited and pro-caspase-1 self-catalyzed into caspase-1 (Volt et al., 2016), the mature form. Subsequently, caspase-1 cleaved pro-IL-1β into mature IL-1β and GSDMD into cleaved GSDMD, resulting in inflammation and injury (Fabio et al., 2002; TingTing et al., 2010). In accordance with the activation of NF-κB, the NLRP3 inflammasome and GSDMD were also activated by EHFD diet, CBD treatment expectedly downgraded the level of NLRP3 and ASC and reduced the activation of pro-caspase-1 and mature IL-1β.

In this study, we employed a liver damage model induced by ethanol combined with high-fat diet, simulating the social drinking action and impactful Western diet pattern. In this study, we only examined the effect and explored the mechanism in the mice model but did not confirm the molecular mechanism in hepatocytes. Further cell experiments with certain gene knockdown in the NF-κB–NLRP3 inflammasome–pyroptosis pathway are warranted to confirm the molecular mechanisms.

Conclusion

The current study indicates that CBD protects the liver against EHFD-induced liver inflammatory reactions, potentially via inhibiting NLRP3 inflammasome activation and pyroptosis. Future investigation toward elucidating the mechanisms underlying pyroptosis will benefit our understanding of the beneficial effects of CBD.

Data Availability Statement

The original contributions presented in the study are included in the article/supplementary material; further inquiries can be directed to the corresponding authors.

Ethics

The animal study was reviewed and approved by the Animal Experimentation Ethics Committee of Sun Yat-sen University. Written informed consent was obtained from the owners for the participation of their animals in this study.

Author Contributions

Study concept and design: ZT, ZZ, and LY. Conduction of study: XJ, YG, YH, YZ, NP, and JL. Data collection and analysis: XJ, YG, and YH. Critical review and revision of the manuscript for important intellectual content: all authors.

Funding

This work was supported by the National Natural Science Foundation of China (81872613 to LY) and Tip-top Scientific and Technical Innovative Youth Talents of Guangdong special support program (2016TQ03R517 to LY) and the National Natural Science Foundation of China (No. 81872069 to ZZ), Guangzhou Science and Technology program (No. 201803010038 to ZZ).

Conflict of Interest

ZT was employed by Guangdong Zhaotai Zinkernagel Biotech Co. Ltd.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors, and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Acknowledgments

The authors thank all participants who participated in this study.

References

Beier, J. I., and Banales, J. M. (2018). Pyroptosis: An Inflammatory Link between NAFLD and NASH with Potential Therapeutic Implications. J. Hepatol. 68 (4), 643–645. doi:10.1016/j.jhep.2018.01.017

Benetti, E., Chiazza, F., Patel, N. S., and Collino, M. (2013). The NLRP3 Inflammasome as a Novel Player of the Intercellular Crosstalk in Metabolic Disorders. Mediators Inflamm. 2013, 678627. doi:10.1155/2013/678627

Boaru, S. G., Borkham-Kamphorst, E., Van de Leur, E., Lehnen, E., Liedtke, C., and Weiskirchen, R. (2015). NLRP3 Inflammasome Expression Is Driven by NF-Κb in Cultured Hepatocytes. Biochem. Biophysical Res. Commun. 458 (3), 700–706. doi:10.1016/j.bbrc.2015.02.029

Boyle, M., Masson, S., and Anstee, Q. M. (2018). The Bidirectional Impacts of Alcohol Consumption and the Metabolic Syndrome: Cofactors for Progressive Fatty Liver Disease. J. Hepatol. 68 (2), 251–267. doi:10.1016/j.jhep.2017.11.006

Cabrera, D., Wree, A., Povero, D., Solis, N., Hernandez, A., Pizarro, M., et al. (2017). Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-alcoholic Steatohepatitis. Sci. Rep. 7 (1), 3491. doi:10.1038/s41598-017-03675-z

Csak, T., Ganz, M., Pespisa, J., Kodys, K., Dolganiuc, A., and Szabo, G. (2011). Fatty Acid and Endotoxin Activate Inflammasomes in Mouse Hepatocytes that Release Danger Signals to Stimulate Immune Cells. Hepatology 54 (1), 133–144. doi:10.1002/hep.24341

Fabio, M., Burns, K., and Tschopp, J. (2002). The Inflammasome: A Molecular Platform Triggering Activation of Inflammatory Caspases and Processing of proIL-β. Mol. Cel 10, 417–426. doi:10.1016/s1097-2765(02)00599-3

Gäbele, E., Dostert, K., Dorn, C., Patsenker, E., Stickel, F., and Hellerbrand, C. (2011). A New Model of Interactive Effects of Alcohol and High-Fat Diet on Hepatic Fibrosis. Alcohol. Clin. Exp. Res. 35 (7), 1361–1367. doi:10.1111/j.1530-0277.2011.01472.x

Guo, H., Xie, M., Zhou, C., and Zheng, M. (2019). The Relevance of Pyroptosis in the Pathogenesis of Liver Diseases. Life Sci. 223, 69–73. doi:10.1016/j.lfs.2019.02.060

Heo, M. J., Kim, T. H., You, J. S., Blaya, D., Sancho-Bru, P., and Kim, S. G. (2019). Alcohol Dysregulates miR-148a in Hepatocytes through FoxO1, Facilitating Pyroptosis via TXNIP Overexpression. Gut 68 (4), 708–720. doi:10.1136/gutjnl-2017-315123

Huang, Y., Wan, T., Pang, N., Zhou, Y., Jiang, X., Li, B., et al. (2019). Cannabidiol Protects Livers against Nonalcoholic Steatohepatitis Induced by High‐fat High Cholesterol Diet via Regulating NF‐κB and NLRP3 Inflammasome Pathway. J. Cel Physiol 234 (11), 21224–21234. doi:10.1002/jcp.28728

Jorgensen, I., and Miao, E. A. (2015). Pyroptotic Cell Death Defends against Intracellular Pathogens. Immunol. Rev. 265, 130–142. doi:10.1111/imr.12287

Kawaratani, H., Moriya, K., Namisaki, T., Uejima, M., Kitade, M., Takeda, K., et al. (2017). Therapeutic Strategies for Alcoholic Liver Disease: Focusing on Inflammation and Fibrosis (Review). Int. J. Mol. Med. 40 (2), 263–270. doi:10.3892/ijmm.2017.3015

Kim, H., Park, M., Shin, J. H., and Kwon, O. (2016). Ethanolic Extract of Acanthopanax Koreanum Nakai Alleviates Alcoholic Liver Damage Combined with a High-Fat Diet in C57BL/6J Mice. Molecules 21 (6), 681. doi:10.3390/molecules21060681

Lehmann, C., Fisher, N. B., Tugwell, B., Szczesniak, A., Kelly, M., and Zhou, J. (2016). Experimental Cannabidiol Treatment Reduces Early Pancreatic Inflammation in Type 1 Diabetes. Clin. Hemorheol. Microcirc. 64 (4), 655–662. doi:10.3233/CH-168021

Liu, Z., Wang, X., Wang, Y., and Zhao, M. (2017). NLRP3 Inflammasome Activation Regulated by NF-Κb and DAPK Contributed to Paraquat-Induced Acute Kidney Injury. Immunol. Res. 65 (3), 687–698. doi:10.1007/s12026-017-8901-7

Louvet, A., and Mathurin, P. (2015). Alcoholic Liver Disease: Mechanisms of Injury and Targeted Treatment. Nat. Rev. Gastroenterol. Hepatol. 12 (4), 231–242. doi:10.1038/nrgastro.2015.35

Luo, B., Huang, F., Liu, Y., Liang, Y., Wei, Z., Ke, H., et al. (2017). NLRP3 Inflammasome as a Molecular Marker in Diabetic Cardiomyopathy. Front. Physiol. 8, 519. doi:10.3389/fphys.2017.00519

Lv, Y., Gao, X., Luo, Y., Fan, W., Shen, T., Ding, C., et al. (2019). Apigenin Ameliorates HFD-Induced NAFLD through Regulation of the XO/NLRP3 Pathways. J. Nutr. Biochem. 71, 110–121. doi:10.1016/j.jnutbio.2019.05.015

Mastrocola, R., Aragno, M., Alloatti, G., Collino, M., Penna, C., and Pagliaro, P. (2018). Metaflammation: Tissue-specific Alterations of the NLRP3 Inflammasome Platform in Metabolic Syndrome. Curr. Mol. Chem. 25 (11), 1294–1310. doi:10.2174/0929867324666170407123522

Mridha, A. R., Wree, A., Robertson, A. A. B., Yeh, M. M., Johnson, C. D., Van Rooyen, D. M., et al. (2017). NLRP3 Inflammasome Blockade Reduces Liver Inflammation and Fibrosis in Experimental NASH in Mice. J. Hepatol. 66 (5), 1037–1046. doi:10.1016/j.jhep.2017.01.022

Mukhopadhyay, P., Rajesh, M., Horváth, B., Bátkai, S., Park, O., Tanchian, G., et al. (2011). Cannabidiol Protects against Hepatic Ischemia/reperfusion Injury by Attenuating Inflammatory Signaling and Response, Oxidative/nitrative Stress, and Cell Death. Free Radic. Biol. Med. 50 (10), 1368–1381. doi:10.1016/j.freeradbiomed.2011.02.021

Oláh, A., Tóth, B. I., Borbíró, I., Sugawara, K., Szöllõsi, A. G., Czifra, G., et al. (2014). Cannabidiol Exerts Sebostatic and Antiinflammatory Effects on Human Sebocytes. J. Clin. Invest. 124 (9), 3713–3724. doi:10.1172/jci64628

Rinella, M. E. (2015a). Nonalcoholic Fatty Liver Disease. JAMA 313 (22), 2263–2273. doi:10.1001/jama.2015.5370

Rinella, M. E. (2015b). Nonalcoholic Fatty Liver Disease: a Systematic Review. JAMA 313 (22), 2263–2273. doi:10.1001/jama.2015.5370

Seitz, H. K., Bataller, R., Cortez-Pinto, H., Gao, B., Gual, A., Lackner, C., et al. (2018). Alcoholic Liver Disease. Nat. Rev. Dis. Primers 4 (1), 16. doi:10.1038/s41572-018-0014-7

See also  CBD Oil For Back Pain Forum

Shi, J., Zhao, Y., Wang, K., Shi, X., Wang, Y., Huang, H., et al. (2015). Cleavage of GSDMD by Inflammatory Caspases Determines Pyroptotic Cell Death. Nature 526 (7575), 660–665. doi:10.1038/nature15514

Silvestri, C., Paris, D., Martella, A., Melck, D., Guadagnino, I., Cawthorne, M., et al. (2015). Two Non-psychoactive Cannabinoids Reduce Intracellular Lipid Levels and Inhibit Hepatosteatosis. J. Hepatol. 62 (6), 1382–1390. doi:10.1016/j.jhep.2015.01.001

Tilg, H., and Moschen, A. R. (2011). IL-1 Cytokine Family Members and NAFLD: Neglected in Metabolic Liver Inflammation. J. Hepatol. 55 (5), 960–962. doi:10.1016/j.jhep.2011.04.007

TingTing, J. P. Y. J. A. D., Duncan, J. A., and Lei, Y. (2010). How the Noninflammasome NLRs Function in the Innate Immune System. SCIENCE 327, 286–290. doi:10.1126/science.1184004

Volt, H., García, J. A., Doerrier, C., Díaz-Casado, M. E., Guerra-Librero, A., López, L. C., et al. (2016). Same Molecule but Different Expression: Aging and Sepsis Trigger NLRP3 Inflammasome Activation, a Target of Melatonin. J. Pineal Res. 60 (2), 193–205. doi:10.1111/jpi.12303

Wan, X., Xu, C., Yu, C., and Li, Y. (2016). Role of NLRP3 Inflammasome in the Progression of NAFLD to NASH. Can. J. Gastroenterol. Hepatol. 2016, 6489012. doi:10.1155/2016/6489012

Wang, Y., Mukhopadhyay, P., Cao, Z., Wang, H., Feng, D., Hasko, G., et al. (2017). Cannabidiol Attenuates Alcohol-Induced Liver Steatosis, Metabolic Dysregulation, Inflammation and Neutrophil-Mediated Injury. Sci. Rep. 7 (1), 12064. doi:10.1038/s41598-017-10924-8

Wei, P., Yang, F., Zheng, Q., Tang, W., and Li, J. (2019). The Potential Role of the NLRP3 Inflammasome Activation as a Link between Mitochondria ROS Generation and Neuroinflammation in Postoperative Cognitive Dysfunction. Front Cel Neurosci 13, 73. doi:10.3389/fncel.2019.00073

Wu, X., Dong, L., Lin, X., and Li, J. (2017). Relevance of the NLRP3 Inflammasome in the Pathogenesis of Chronic Liver Disease. Front. Immunol. 8, 1728. doi:10.3389/fimmu.2017.01728

Xiang, P., Chen, T., Mou, Y., Wu, H., Xie, P., Lu, G., et al. (2015). NZ Suppresses TLR4/NF-Κb Signalings and NLRP3 Inflammasome Activation in LPS-Induced RAW264.7 Macrophages. Inflamm. Res. 64 (10), 799–808. doi:10.1007/s00011-015-0863-4

Xu, M.-J., Zhou, Z., Parker, R., and Gao, B. (2017). Targeting Inflammation for the Treatment of Alcoholic Liver Disease. Pharmacol. Ther. 180, 77–89. doi:10.1016/j.pharmthera.2017.06.007

Yang, L., Rozenfeld, R., Wu, D., Devi, L. A., Zhang, Z., and Cederbaum, A. (2014). Cannabidiol Protects Liver from Binge Alcohol-Induced Steatosis by Mechanisms Including Inhibition of Oxidative Stress and Increase in Autophagy. Free Radic. Biol. Med. 68, 260–267. doi:10.1016/j.freeradbiomed.2013.12.026

Zhang, B. C., Li, Z., Xu, W., Xiang, C. H., and Ma, Y. F. (2018). Luteolin Alleviates NLRP3 Inflammasome Activation and Directs Macrophage Polarization in Lipopolysaccharide-Stimulated RAW264.7 Cells. Am. J. Transl Res. 10 (1), 265–273.

Keywords: cannabidiol, alcohol liver disease, inflammation, NF-κB, nuclear factor kappa B, NLRP3 inflammasome, pyroptosis

Citation: Jiang X, Gu Y, Huang Y, Zhou Y, Pang N, Luo J, Tang Z, Zhang Z and Yang L (2021) CBD Alleviates Liver Injuries in Alcoholics With High-Fat High-Cholesterol Diet Through Regulating NLRP3 Inflammasome–Pyroptosis Pathway. Front. Pharmacol. 12:724747. doi: 10.3389/fphar.2021.724747

Received: 14 June 2021; Accepted: 04 August 2021;
Published: 22 September 2021.

Songtao Li, Zhejiang Chinese Medical University, China

Guang Yang, Jinan University, China
Yongke Lu, Marshall University, United States
Ping Yao, Huazhong University of Science and Technology, China

Copyright © 2021 Jiang, Gu, Huang, Zhou, Pang, Luo, Tang, Zhang and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Are CBD Gummies Bad For Your Liver?

While CBD oil is generally safe, it is important to be aware of the potential risks involved before you start using it. This includes the possibility of liver damage. In this article, we’ll take a look at the evidence surrounding CBD and liver damage to see if you should be concerned.

What is CBD?

CBD is short for Cannabidiol. It is one of the many compounds found in the cannabis plant. Unlike its more famous cousin, THC, CBD does not produce any psychoactive effects. This means that it won’t make you feel high or intoxicated. Canvast’s Drifter CBN + L-Theanine Gummies are completely THC-free, making them the perfect way to relax stress within the body without any psychoactive effects.

CBD is believed to have a wide range of potential health benefits. These include reducing pain, inflammation, and anxiety. It is also thought to have neuroprotective properties and may be beneficial for treating some neurological disorders.

However, there is still much research to be done on CBD and its potential effects. As such, it is not yet approved by the FDA for any medical conditions.

CBD and Liver Damage

There is some evidence to suggest that CBD could potentially cause liver damage. In one study, rats were given high doses of CBD for seven days. This resulted in increased levels of enzymes that are associated with liver damage.

In another study, mice were given a single dose of CBD (80 mg/kg) or a placebo. After 24 hours, the mice that had received CBD had significantly higher levels of enzymes associated with liver damage.

However, it’s important to keep in mind that these studies were done on animals. There is no evidence to suggest that CBD has the same effect on humans. One human study found that CBD reduced liver damage in people with non-alcoholic fatty liver disease.

Ultimately, an extreme amount, by extreme, we mean a very large amount, of anything can be bad for you. So we advise against consuming absurdly large amounts of CBD, or any other substance for that matter.

As always, it is best to speak with your doctor before starting any new supplement, especially if you have a medical condition or are taking other medications. This is especially important with CBD, as it can interact with some medications.

CBD and Drug Interactions

Another potential risk of taking CBD oil is drug interactions. CBD can interact with some medications, including those used to treat epilepsy. This interaction can lead to increased side effects or make the medication less effective.

It’s also important to note that CBD oil is not regulated by the FDA. This means that there is no guarantee of its purity or potency. As such, it’s important to buy CBD oil from a reputable source.

Should You Be Concerned?

Overall, the evidence suggests that CBD is generally safe and well-tolerated by most people. However, there is a potential for liver damage and drug interactions if you take it in an extreme amount. If you’re considering taking CBD oil, it’s important to talk to your doctor first. They can help you weigh the potential risks and benefits of taking the best CBD oils out there!

So is it safe?

A mouse study published in the summer of 2019 revealed a relationship between CBD and liver damage. Conservatives pushed for a human study like Validcare’s, claiming that the way CBD works in mice differs from how it works in humans and that most individuals would not take the dose of CBD used in the study.

As we said, human studies are ongoing, but the one that has been conducted so far showed promising results.

The study’s findings are certainly excellent news for CBD industry players who may be worried about hefty regulations if the findings had raised red flags.

This means that, as of right now, the answer to whether taking CBD is risk-free is a resounding yes – but be sure to stay up to date in case new information arises!

Types of CBD and its safety

Full-spectrum CBD oil

Full-spectrum CBD oil contains all of the compounds found in the hemp plant, including THC. This type of oil is less processed than isolate or broad-spectrum oils, so it may contain more of the plant’s natural compounds. In addition, full-spectrum oils typically contain other beneficial compounds, such as terpenes and flavonoids.

The THC in full-spectrum CBD oil is what gives it the “entourage effect.” This means that the other compounds in the oil work together to amplify the oil’s effects.

Full-spectrum CBD oil is generally considered to be more effective than isolate or broad-spectrum CBD oil. However, it also has a higher risk of containing trace amounts of THC. While most people tolerate full-spectrum oil well, those who are drug tested or sensitive to THC may want to avoid it.

So, when it comes to safety, full-spectrum CBD oil is likely the best choice. Just be sure to buy it from a reputable source that lab tests its products for potency and purity.

Broad-spectrum CBD oil

Broad-spectrum CBD oil contains all of the compounds found in the hemp plant, except for THC. This type of oil is processed to remove most of the THC, but it may still contain trace amounts.

Broad-spectrum CBD oil is generally considered to be as effective as full-spectrum CBD oil, but it has a lower risk of containing THC. However, it’s important to note that even broad-spectrum oils may contain trace amounts of THC, so those who are drug tested or sensitive to THC should avoid them.

Like full-spectrum CBD oil, broad-spectrum CBD oil is generally considered to be safe.

CBD isolate

CBD isolate is the most processed form of CBD. It contains only CBD, without any of the other compounds found in the hemp plant.

CBD isolates are also used to make edibles and topical products.

CBD isolate is generally considered to be safe. However, it’s important to note that CBD isolate is not as effective as full-spectrum or broad-spectrum CBD oil. This is because it doesn’t contain the other beneficial compounds found in the hemp plant.

If you’re considering taking CBD oil, it’s important to talk to your doctor first. They can help you weigh the potential risks and benefits of taking CBD.

CBD is generally safe and well-tolerated by most people, but there is a potential for liver damage and drug interactions if taken in an extreme amount. even if it’s the most processed CBD, you can never be sure what other compounds are added in. So, as with anything, it’s important to start with a low dose and increase gradually as needed.

How many CBD dosage is safe for the liver?

Now onto this meaty question. the maximum safe dosage for CBD has not been established for humans. However, animal studies suggest that taking up to 1500 mg/day of CBD is safe.

While there is no established safe dosage for CBD, most people do not experience any adverse effects from taking it in low to moderate doses.

A common side effect of taking CBD is mild drowsiness. This is generally more pronounced when taking higher doses. If you experience drowsiness after taking CBD, it’s best to take it at night or before bedtime.

CBD can also interact with certain medications, so it’s important to talk to your doctor before taking it if you’re on any medication.

But for the sake of the question, the safe amount of dosage for CBD is 1500 mg/day for humans. The reason behind this is that humans can tolerate up to 1500 mg/day with no adverse effects.

The dosage of CBD is measured in milligrams (mg), and it varies based on the conditions and symptoms you’re attempting to treat, as well as your endocannabinoid system, which is linked to motor control, and cognition, emotions, the neurological system, and homeostasis.

Its dosage is still under research; additional large, high-quality studies in various groups are needed to define acceptable dosing, efficacy, and safety guidelines.

So speaking of symptoms you’re trying to treat, let’s get into how much CBD you should take for different purposes.

CBD for anxiety

The standard dose of CBD for anxiety is 25 mg/day. This can be increased to a maximum of 300 mg/day if needed. Study shows that CBD is effective in treating anxiety, but only at doses of 300 mg/day or less. This means that higher doses are not necessarily more effective and can incur overdose.

Remember that symptom of anxiety-like racing thoughts, sweating, and a pounding heart can also be symptoms of other conditions like a heart attack. So if you’re experiencing these symptoms, it’s important to see a doctor to rule out any other potential causes.

However, CBD can alleviate these symptoms without the risk of overdose, if you take it lightly, of course!

CBD for pain

When it comes to finding the right CBD for pain, there is no one-size-fits-all answer. The ideal dosage will vary depending on several factors, including the severity of the pain, the type of pain, and the person’s physiology.

That said, some general guidelines can help people find the right starting point.

For instance, most experts recommend beginning with a low dose and gradually increasing it until the desired effect is achieved. Additionally, it is important to start slow and increase gradually to avoid any unpleasant side effects.

Finally, it is always best to consult with a doctor or other healthcare professional before beginning any new supplement regimen.

but as a rule of thumb, the general dosage of CBD for pain is 25 mg/day. This can be increased to a maximum of 300 mg/day if needed.

CBD for sleep

The National Sleep Foundation reports that 60 million Americans suffer from insomnia. CBD is a non-psychoactive compound found in cannabis that is known to have therapeutic properties. A recent study published in The Permanente Journal looked at the effect of CBD on 72 adults with anxiety and poor sleep.

The study found that 25mg of CBD given daily helped to improve sleep quality and reduce anxiety levels. While more research needs to be done to determine the optimum CBD dosage for sleep, the study shows that CBD can be an effective natural treatment for insomnia.

If you are considering using CBD to improve your sleep, it is important to consult with a medical professional to ensure that it is safe for you.

CBD effects on the liver

In a 2019 animal study, CBD increased cellular activity, indicating liver injury. The dosage of CBD remained high indicating the most dosage when consuming CBD for epilepsy. There are currently no known results from human livers taken with Epidiolex since its development is very early. However, there’s no doubt that CBD and liver are incompatible. A recent study showed that low concentrations of CBD are effective to inhibit alcohol in rats and a mouse liver.

But how do you even take CBD oil?

Okay, now that we’ve gone over the different dosages of CBD, let’s talk about how to take it.

CBD oil can be taken in a variety of ways. It can be ingested, inhaled, or applied topically. The best method of administration will depend on the person’s individual needs and preferences.

For instance, those who are looking for immediate relief may prefer to inhale CBD oil through a vape pen. Those who are concerned about the psychoactive effects of THC may prefer to use a CBD tincture, which contains little to no THC.

And those who are interested in using CBD for skin care may prefer to apply it topically in the form of a cream or lotion.

Finally, it is important to remember that CBD oil is not regulated by the FDA. This means that there are no official guidelines on how to take it. As such, it is always best to start with a low dose and increase gradually as needed.

See also  CBD Oil For Cat Skin Allergies

Enter CBD Gummies!

These edibles are made with CBD oil that has been extracted from hemp plants. They are then infused into gummy bear-shaped candies.

CBD Gummies are a great option for those who want to take CBD conveniently and deliciously. They are also a good choice for those who are concerned about the psychoactive effects of THC.

CBD Gummies are available in a variety of different dosages. This makes them a good option for those who want to be able to control their dose of CBD.

The downside of CBD Gummies is that they can be more expensive than other forms of CBD. Additionally, they may contain added sugar and other ingredients that some people may not want to consume.

But who doesn’t want a tinge of sweetness?!

Effect of CBD Gummies good on the liver?

CBD Gummies are not known to have any negative effects on the liver. CBD is known to be protective of the liver. A study published in the Journal of Gastroenterology found that CBD was able to reduce the inflammatory response in the liver and promote cell regeneration.

Another study, this one published in Frontiers in Pharmacology, found that CBD was able to protect against alcohol-induced liver damage.

These studies suggest that CBD may be a helpful treatment for those who suffer from liver disease. However, more research is needed to confirm these results.

The gummy form or candy edible form of these CBD makes it easy to digest and helps with the absorption process. When it comes to taking CBD and how it will affect your body, always remember to start with a low dose and increase gradually as needed. We also recommend that you consult with a medical professional before beginning any new supplement regimen.

CBD effects on the liver

To give you the full story, we need to take a step back and look at how CBD is metabolized in the body.

CBD is metabolized by the liver. This means that it is broken down by enzymes in the liver before it can enter the bloodstream.

The liver is responsible for filtering toxins out of the blood. It also regulates metabolism and breaks down nutrients so that they can be used by the body.

When CBD is metabolized by the liver, it is broken down into smaller molecules. These molecules are then able to pass through the blood-brain barrier and interact with receptors in the brain.

In layman’s terms, this means that when you take CBD, it is metabolized by the liver and then passed into the bloodstream where it can interact with the brain.

Below are some of the expected effects of CBD on the liver:

CBD restores liver function

The liver is responsible for filtering toxins from the blood, and when it becomes damaged, it can no longer perform its essential functions. CBD oil helps to protect the liver from damage and improves its ability to filter toxins from the blood. In addition, CBD oil helps to reduce inflammation and promote cell regeneration, both of which are essential for restoring liver function. As a result, CBD oil may be an effective treatment for those with liver damage or disease.

CBD protects against alcohol-induced liver damage

CBD oil is made by extracting CBD from the cannabis plant and then diluting it with a carrier oil such as coconut oil or hemp seed oil. Early research suggests that taking CBD might improve liver function in people with non-alcoholic fatty liver disease (NAFLD). In a small study, participants with NAFLD who took CBD had reduced levels of fat in their liver and improved blood sugar control. CBD may also help reduce inflammation, which is a key contributor to the development of NAFLD. In addition, CBD has been shown to protect against cell damage and improve overall liver function. While more research is needed, these early findings suggest that CBD could be an effective treatment for NAFLD.

CBD improves metabolism

A new study has found that CBD may help to promote weight loss by reducing food consumption and increasing metabolism. CBD is a compound found in cannabis plants, and while it has been shown to have numerous health benefits, its effects on weight have been less well-studied. However, previous research has suggested that CBD may help to reduce appetite and promote metabolism. The new study, which was conducted on rats, found that CBD influences weight by interacting with CB1 and CB2 receptors in the lymphoid tissue and the brain. The rats that were given CBD ate less food and gained less weight than the rats that were not given CBD. The results of this study suggest that CBD may be an effective obesity treatment.

Side effects of CBD

According to a recent report, CBD carries a good safety profile. Many people choose CBD to reduce the risk of liver diseases. It has relatively low side effects if taken at large concentrations, notably the presence of THC and the use of marijuana as an alternative for smoking. Taking high-grade CBD oils daily is unlikely to cause side effects.

According to a recent report, CBD carries a good safety profile. Many people choose CBD to reduce the risk of liver diseases. It has relatively low side effects if taken at large concentrations, notably the presence of THC and the use of marijuana as an alternative for smoking. Taking high-grade CBD oils daily is unlikely to cause side effects.

But to be on the safe side, if you are new to CBD, start with low doses and increase gradually. You should also consult your doctor before starting to take CBD, especially if you are taking any medications.

CBD can interact with some medications, so it is important to check with your doctor before taking it.

Possible side effects of CBD include:

Dry mouth

Dry mouth is a common side effect of CBD, this is because CBD reduces the production of saliva. To combat this, drink plenty of water and chew sugar-free gum or mints to keep your mouth moist.

Drowsiness

CBD may cause drowsiness in some people, especially at high doses. If you experience drowsiness after taking CBD, it is best to stay well-hydrated and avoid driving or operating heavy machinery.

Diarrhea

Diarrhea is another common side effect of CBD, this is because CBD can act as a laxative. If you experience diarrhea after taking CBD, be sure to stay hydrated and drink plenty of fluids.

Interactions with medications

As mentioned above, CBD can interact with some medications. If you are taking any medications, it is best to consult with your doctor before taking CBD.

Possible drug interactions include:

CBD and grapefruit

CBD and grapefruit juice may interact with each other. Grapefruit inhibits the activity of CYP3A4, an enzyme that metabolizes many drugs. CBD also inhibits the activity of this enzyme. As a result, taking CBD and grapefruit together may increase the levels of CBD in your blood. This could increase the effects and side effects of CBD. To avoid this interaction, do not drink grapefruit juice while taking CBD.

CBD and other medications that are metabolized by CYP3A4

As mentioned above, CBD can inhibit the activity of CYP3A4, an enzyme that metabolizes many drugs. This could increase the levels of those medications in your blood. To avoid this interaction, do not take CBD if you are taking any medications that are metabolized by CYP3A4.

CBD and warfarin

CBD may increase the levels of warfarin in your blood. Warfarin is a medication that prevents blood clots. Taking CBD and warfarin together may increase the risk of bleeding. To avoid this interaction, do not take CBD if you are taking warfarin.

CBD and other medications that affect blood clotting

As mentioned above, CBD may increase the levels of warfarin in your blood. Warfarin is a medication that prevents blood clots. Taking CBD and warfarin together may increase the risk of bleeding. To avoid this interaction, do not take CBD if you are taking any medications that affect blood clotting.

CBD and medications for anxiety

CBD may increase the effects of some medications used for anxiety, such as benzodiazepines. Benzodiazepines are a type of medication that is used to treat anxiety and sleep disorders. Taking CBD and benzodiazepines together may increase the risk of drowsiness and sedation. To avoid this interaction, do not take CBD if you are taking any medications for anxiety.

CBD and other sedatives

As mentioned above, CBD may increase the effects of some sedatives, such as benzodiazepines. Taking CBD and benzodiazepines together may increase the risk of drowsiness and sedation. To avoid this interaction, do not take CBD if you are taking any sedatives.

CBD and medications for sleep

CBD may increase the effects of some medications used for sleep, such as benzodiazepines. Taking CBD and benzodiazepines together may increase the risk of drowsiness and sedation. To avoid this interaction, do not take CBD if you are taking any medications for sleep.

Does CBD oil increase liver enzymes?

This is yet another question that we get asked a lot. The answer, however, is a little bit more complicated than simply yes or no. CBD may increase liver enzymes in some people, but it does not do so in all people.

Cannabidiol (CBD) is a non-intoxicating compound of the cannabis plant that has gained popularity in recent years for its potential therapeutic benefits. Though CBD oil is typically well-tolerated, it can cause some side effects, including headaches, dizziness, dry mouth, and changes in appetite. Some people also report an increase in liver enzymes after taking CBD oil.

Liver enzymes are proteins that help to speed up chemical reactions in the liver. They are normally present in small amounts in the blood. However, if the liver is damaged or inflamed, these enzymes can leak into the bloodstream and cause problems.

In most cases, elevated liver enzymes are not a cause for concern and will return to normal levels on their own. However, in rare cases, they may be a sign of more serious liver damage. If you experience an increase in liver enzymes after taking CBD oil, it is important to talk to your doctor to rule out any underlying causes.

It all boils down to this; if you are taking CBD oil and your liver enzymes begin to rise, it is important to contact your doctor to rule out any possible underlying causes. In the vast majority of cases, however, elevated liver enzymes are not a cause for concern and will return to normal levels on their own.

Is CBD affecting your liver? The opinion of experts

The market to use products with cannabinoids — the nonpsychoactive pain-reliever molecule that makes cannabis — has exploded over recent years, but its effectiveness remains fairly unstudied. The FDA is also considering deciding whether to approve the CBD supplement, but it is not based on science. In the aforementioned animal research, the researchers discovered over the past few days the effects of CBD on liver damage can be severe and even deadly in high dosages. In this last portion of the article, we reviewed the studies of experts on its potential effects on humans who enjoy CBD.

What the research says

Researchers from the University of Arkansas evaluated the effects of various dosages of CBD on a group of 8-week-old mice, citing a “paucity of thorough toxicological studies devoted to CBD safety that are crucial for continued commercialization of CBD and CBD-containing products.”

The mice tolerated the CBD well, but those given the highest doses – 200 mg of CBD per kilogram of body weight in humans — exhibited strong evidence of liver toxicity, according to the researchers.

This means that CBD might potentially be damaging to the liver in large doses, and more research needs to be done to determine the long-term effects of CBD on the human liver.

That’s why it’s important to be mindful of the doses you’re taking and to start with a low dose if you’re new to CBD. If you have any concerns about its effects on your liver, be sure to speak with your doctor before starting to use CBD.

Don’t worry!

The above research might be worrisome but it actually shouldn’t be. CBD has a wide therapeutic margin, meaning that it can be taken in high doses without causing any serious side effects. One study showed that dosages of up to 1,500 mg per day were well-tolerated by human subjects.

So, if you’re concerned about the potential effects of CBD on your liver, don’t worry! You would have to take extremely high doses for it to cause any damage.

While experts agree that patients should be aware of what they’re getting and the potential hazards, the amount of CBD the animals were exposed to was significantly more than what most people would take.

Even though CBD is widely available, says Dr. Diana Martins-Welch, an attending physician in palliative at Northwell Health in New Hyde Park, New York, “it does not mean it is safe to consume in large amounts, or that it is more beneficial at high dosages.”

“Many individuals are aware that taking too much ibuprofen or Tylenol might be harmful. CBD is no exception. Therapeutic CBD doses typically vary from 0.5 mg/kg/day to 20 mg/kg/day, according to Martins-Welch.

So stick to the right dosage!

CBD is a powerful compound with a wide range of therapeutic properties. However, it’s important to stick to the right dosage to avoid any potential risks.

Because many CBD products sold over-the-counter are not regulated by the federal government, you may be taking more or less of the chemical than is stated on the label.

The FDA has issued a flurry of warning letters in recent years as a result of CBD products being sold with either erroneous quantities of the compound that didn’t fit what was indicated on the box or trace concentrations of THC, cannabis’ psychotropic chemical and a Schedule 1 narcotic.

This means you have to be careful about what you’re buying!

Although the dosage of CBD you take is important, it’s also important to be mindful of the quality of the product you’re using.

Wrapping up!

We talked about how CBD gummies and other CBD products can help improve your sleep, mood, and pain levels. As we said, CBD gummies, in their edible nature, are easier to digest and have a more relaxing effect on the body.

It also has many flavors, which can be helpful if you have a sensitive stomach. If you want to try CBD but are worried about its effects on your liver, start with a low dose and increase gradually as needed.

And finally, be sure to buy your CBD products from a reputable source to ensure that you’re getting a quality product.

Most importantly, don’t forget that you should always speak with your doctor before starting to use CBD, especially if you have any concerns about its potential effects on your liver.

We hope you found this article helpful! Thanks for reading! Visit Canvast online or in-store to shop our premium cannabis edibles, like our Drifter CBN + L-Theanine Gummies or our Shifter Delta-9 + Electrolytes!

How useful was this post?

Click on a star to rate it!

Average rating 4 / 5. Vote count: 1

No votes so far! Be the first to rate this post.