Keywords: hepatic encephalopathy, cannabidiol, cognition, liver enzymes, Cannabidiol (CBD) is a non-psychoactive ingredient of Cannabis sativa (Izzo et al. May 7, There also is some indication that CBD might harm the liver. About 10 percent of people taking CBD in studies had increases in liver enzymes. A collection of published research articles and other educational resources about liver disease and CBD (cannabidiol).
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Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment.
Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. Hepatic encephalopathy HE is a syndrome observed in patients with end-stage liver disease. It is defined as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunction, after exclusion of other known brain diseases, and is characterized by personality changes, intellectual impairments and a depressed level of consciousness associated with multiple neurotransmitter systems, astrocyte dysfunction and cerebral perfusion Riggio et al.
HE, accompanying the acute onset of severe hepatic dysfunction, is the hallmark of fulminant hepatic failure FHF , and patients with HE have been reported to have elevated levels of ammonia in their blood Stahl, This infiltration was shown to be associated with activation of the cerebral endothelium and an increase in the expression of adhesion molecules Kerfoot et al.
Many mechanisms have been suggested for its action, such as agonism of 5-HT 1A receptors Russo et al. It also has a very strong anti-inflammatory activity both in vivo , as an anti-arthritic therapeutic Malfait et al. The finding that CBD is devoid of any psychotropic effects combined with its anti-inflammatory activity makes it a promising tool for treating HE, which is exacerbated by an inflammatory response Shawcross et al.
In the present work, we aimed to explore the effects of CBD in the acute model of HE induced by the hepatotoxin thioacetamide TAA , focusing on brain function, brain pathology and 5-HT levels, liver function and pathology as possible targets for therapeutic effects of CBD. Female Sabra mice 34—36 g , 8 to 10 weeks old, were assigned at random to different groups of 10 mice per cage and were used in all experiments. The mice had free access to water 24 h a day.
Mice were killed after each treatment by decapitation between 10h00min and 12h00min. Animals were kept at the animal facility in accordance with NIH guidelines and all experiments were approved by the institutional animal use and care committee, No.
We adapted the rat model of acute liver failure induced by TAA to mice Zimmermann et al. The TAA model in mice has been extensively validated previously Honda et al. Vehicle NS was also administered in a separate group of animals that served as controls. Twenty-four hours after injection of TAA all animals including control were injected s. The mice were intermittently exposed to infrared light in order to prevent hypothermia.
CBD was extracted from cannabis resin hashish and purified as previously reported Gaoni and Mechoulam, and was dissolved in a vehicle solution consisting of ethanol, emulphor and saline at a ratio of 1: Four groups of animals were studied: Neurological function was assessed by a point scale based on reflexes and task performance Chen et al. For each task failed or abnormal reflex reaction a score of 1 was assigned.
Thus, a higher score indicates poorer neurological function. The neurological score was assessed 1 day after induction of hepatic failure by TAA day 2. The mice were then divided between treatment groups so that all groups had similar baseline neurological scores after TAA induction.
The post-treatment neurological score was assessed 1 day after administration of CBD or vehicle day 3. The activity test was performed 2 days after the induction of hepatic failure. Activity of two mice was measured simultaneously for a 5 min period. Two mice were tested together to lower stress to the minimum, as it has been shown that separation of mice induces stress van Leeuwen et al.
Locomotor activity was recorded by counting the number of crossings by the mice at 1 min intervals. Cognitive function studies were performed 8 days after the induction of hepatic failure. The animals were placed in an eight-arm maze, which is a scaled-down version of that developed for rats Olton and Samuelson, ; Pick and Yanai, Animals were divided between treatment groups so that all groups had similar baselines neurological scores after TAA induction. The mice were tested no.
Hence, the lower the score the better the cognitive function. Food and water were given at the completion of the test. Maze performance was calculated on each day for five consecutive days. Results are presented as area under the curve AUC utilizing the formula: The brain was cut along the midline and separated into two pieces containing brain and cerebellum hemispheres. These slides were used for glial fibrillary acidic protein GFAP immunohistochemistry a total of 90 sections , according to standard protocol.
Briefly, paraffin sections were deparaffinized and hydrated in xylene and alcohol solutions, rinsed with tris buffer saline. Citrate buffer pH 6 was used for antigen retrieval. The endogenous peroxidase was blocked with H 2 O 2 0. Sections were then incubated in blocking buffer for 1 h. A series of reselected sections were then treated with primary antibody against GFAP 1: Immunoreactions were visualized with the avidin—biotin complex Vectastain and the peroxidase reaction was visualized with diaminobenzidine DAB Vector , as chromogen.
Sections were finally counterstained with haematoxylin and examined under light microscope Zeiss Axioplan 2. Astrocytes were evaluated at the hippocampal area of both hemispheres. A total of five to seven randomly selected visual fields per hemisphere section were evaluated. Only those cells with an identifiable nucleus were counted. Two independent observers who were blinded to sample identity performed all quantitative assessments.
In cases where significant discrepancies were obvious between the two observers, the evaluation was repeated by a third one. Liver histopathological analysis and scoring of necrosis coagulative, centrilobular were performed as described previously Avraham et al. Serum for alanine transaminase ALT , aspartate transaminase AST , bilirubin and ammonia measurements was obtained on day 3 in glass tubes, centrifuged, and analysed on the day of sampling using a Kone Progress Selective Chemistry Analyzer Kone Instruments, Espoo, Finland.
All serum samples were processed in the same laboratory using the same methods and the same reference values. On day 12, mice killed by decapitation and their brains were dissected out for determination of 5-HT levels. Blood was drawn and separated for plasma, in which liver enzymes were quantified. This was identical to experiment 1 on days 1—3, only the mice were not killed on day 3 but were evaluated for cognitive function using the eight-arm maze test, on days 8— On day 12, the mice were killed and their livers and brains were dissected out for determination of 5-HT levels.
Food and Drug Administration advisory panel unanimously recommended approval of the CBD medication Epidiolex to treat two rare forms of childhood epilepsy. For the rest of CBD's potential uses, there is simply too little evidence to make a firm conclusion.
For example, some human clinical trials suggest that CBD could be effective in treating symptoms of anxiety, particularly social anxiety, Bonn-Miller said. This is the potential use for CBD with the most evidence after usefulness in epilepsy, but "there's a decent gap between those two," he said.
CBD's usefulness as an anti-inflammatory medication is the next most promising, but those results come mostly from animal studies, experts said. The rest of the potential uses -- as an antipsychotic, antidepressant or sleep aid "have all been studied in animals, with only one or two examples of studies in humans," Bonn-Miller said.
And Welty said the studies that have featured humans for these other CBD uses have either been case reports or studies that did not compare results against a control group that did not use the oil. There also are concerns about both the quality of CBD oil being produced and its potential side effects, the experts added.
States are struggling to put regulations in place, but they don't have the deep pockets of the federal government. Meanwhile, a study led by Bonn-Miller found that nearly 7 of 10 CBD products didn't contain the amount of marijuana extract promised on the label.
Nearly 43 percent of the products contained too little CBD, while about 26 percent contained too much, Bonn-Miller said. This list is by no means a reflection on the full extent of CBD , however.
As more research is done into this incredible cannabinoid, we are finding even more situations where CBD may just be the best natural option for patients! It seems that there are many ways that CBD consumption can benefit the disease, both with the symptoms and also in terms of preventing it all together!
We know from years of research, for example, that CBD is a potent anti-inflammatory compound, and it is this property in particular that has provided such a powerful effect on ALD.
A study was done in that showed how CBD could help reduce inflammation in a chronically damaged liver. The study which was done on mice revealed a significant reduction in inflammation when administered with the non-psychoactive compound.
CBD is a well-known anti-oxidant, for instance, and a study published in revealed that it could prevent oxidative stress, which ultimately results in further liver damage as a result of excess alcohol consumption. The group was split into three groups, and the results showed as follows:.
The results from this study ultimately revealed that those most dependent on alcohol had the most significant protection from cannabis use. However, this is certainly not to say that people who abuse alcohol should also abuse cannabis.
At the end of the day, the studies simply have provided a great eye-opener into the abilities of CBD and cannabis as a whole for treatment in this area! While marijuana advocates the world over continue to fight the good fight to make cannabis legal across the board, there are still many states that hold incredibly tight laws.
As research plows on, though, we live in the hope that this will soon change! Leave a Reply Cancel reply.
CBD For Alcohol Liver Disease and Disorders (ALD)
May 16, New studies are exploring how cannabis might help the liver . found that CBD is helpful in causing malignant cells found in liver fibrosis to. Jan 22, Here's what you need to know about cannabis and liver disease. In fact, CBD was able to restore normal liver functioning in the mice. MONDAY, May 7, (HealthDay News) -- Cannabidiol (CBD) oil has become the hot new . There also is some indication that CBD might harm the liver.