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Liver Disease and Sex: An Informative Guide

Is CBD Safe for You and Your Liver?

This article examines various studies on the safety of CBD for you and your liver. We expose missing details and unanswered questions concerning a recent, controversial study claiming that CBD can damage your liver.

These days, everyone is saying CBD is this miracle substance that can potentially remedy multiple ailments – from insomnia to pain, to even possibly helping cope with cancer treatment – with little to no side effects.

But, while many people are on board with trying this possible miracle drug, some are questioning if CBD is actually as safe for your liver as it’s cracked up to be.

The Controversial Study on CBD and Liver Safety: The Test Was Flawed from the Start

In an article, “Marijuana Study Finds CBD Can Cause Liver Damage,” published by Forbes.com on June 18, 2019, the contributor seems to be trying to scare people with liver issues into not trying CBD – by not telling the complete story.

The contributor references a study performed on mice published in the April 2019 edition of the Molecules Journal titled Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model. In this study, researchers at the University of Arkansas for Medical Sciences were trying to determine if hepatotoxicity was possible in mice that were consistently given high volumes of CBD oil.

Tests on 2 Groups of Mice

They performed various tests on two groups of mice. In the first group labeled, the acute toxicity group, the mice were given varying concentrations of 0, 246, 738, or 2,460 mg/kg of CBD.

In the second group labeled, the sub-acute toxicity group, the mice were given varying concentrations of 0, 61.5, 184.5, or 615 mg/kg of CBD.

In the second group, 75% of the mice that were given the 615 mg dosage either died or were dying within 72-96 hours. They exhibited symptoms of liver damage that were similar to those of the mice given the highest dosages in the acute phase (increases in LBW ratios, ALT, AST, and total bilirubin).

What the contributor failed to tell you is the results above were based on dosages of 615 mg or more of CBD, which are all extremely high dosages of CBD.

How to Convert the CBD Dosages Used in the Mice to Equivalent Human Dosages

If you take the maximum dosages for each group (615 mg and 2,460 mg) and convert them to equivalent human dosages, the amount of CBD a human would be given is totally unrealistic and would never be taken.

  • Group 1: Acute toxicity group max dosage level – 2,460 mg/kg
  • Group 2: Sub-acute toxicity group max dosage level – 615 mg/kg

Now let’s convert that to an average adult human being weighing 150 lbs.

  1. Step 1: Convert pounds to kilograms. 150 lbs = 68 kg
  2. Step 2: Multiply the milligrams of CBD given to the mice in each group by the kilograms of weight of the human.
  • Group 1 – 2,460 mg x 68 kg = 167,280 mg of CBD per day
  • Group 2 – 615 mg x 68 kg = 41,820 mg of CBD per day

As you can see, you would never take the comparable dosage when converted to the weight of a human being. The test was flawed from the start.

Epidiolex

The contributor then refers to an FDA-approved drug containing CBD called Epidiolex which is recommended for children with severe epilepsy.

It is worth noting that Epidiolex is only given to children who are suffering from epileptic seizures when conventional drugs don’t work. It is not for everyone. Epidiolex went through many trials, and liver damage is listed as a side effect and has a liver warning associated with it.

The actual results and facts are listed below.

Epidiolex does not require dose adjustment in patients with mild (Child-Pugh A) hepatic impairment, but dose adjustment is recommended in patients with moderate (Child-Pugh B) hepatic impairment or severe (Child-Pugh C) hepatic impairment.

Details of the Dose Adjustments in Patients with Hepatic Impairment

Hepatic Impairment Starting Dosage Maintenance Dosage Maximum Recommended Dosage
Mild: Normal dosage given – no adjustment required 2.5 mg/kg twice daily (5 mg/kg/day) 5 mg/kg twice daily (10 mg/kg/day) 10 mg/kg twice daily (20 mg/kg/day)
Moderate 1.25 mg/kg twice daily (2.5 mg/kg/day) 2.5 mg/kg twice daily (5 mg/kg/day) 5 mg/kg twice daily (10 mg/kg/day)
Severe 0.5 mg/kg twice daily (1 mg/kg/day) 1 mg/kg twice daily (2 mg/kg/day) 2 mg/kg twice daily (4 mg/kg/day)

 

The trials did find, at the regular dosages given, Epidiolex could cause dose-related elevations of liver transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST].

However, you were not told that, in about two-thirds of the cases the liver issues were resolved by discontinuation of Epidiolex or reduction in Epidiolex dosage. And, in one-third of the cases, the liver issues were resolved during continued treatment of Epidiolex, without dose reduction.

Below is a chart that details the number of patients in the trials and the percentage of them who actually had elevated liver enzymes. If you look closely, you will see the Placebo group, which did not receive any Epidiolex, also had 3% of its patients achieve elevated liver issues.

Adverse Reactions in Patients Treated with Epidiolex in Controlled Trials

Dosage Number of Patients in Trials Percentage of Patients with Elevated Liver Issues
Placebo 227 3%
10 mg/kg/day 75 8%
20 mg/kg/day 238 15%

 

So, even the group that did not take any Epidiolex had patients with elevated liver issues.

How Much CBD Were They REALLY Given

If we use the same calculations we performed above, but this time on a child weighing 75 lbs, they were given the following:

Dosage Milligrams of CBD for a child weighing 75 lbs.
5 mg/kg/day 170 milligrams
10 mg/kg/day 340 milligrams
20 mg/kg/day 680 milligrams

 

Now let’s convert the dosage from a child’s dosage to an average adult weighing 150 lbs.

Dosage Milligrams of CBD for an average adult weighing 150 lbs.
5 mg/kg/day 340 milligrams
10 mg/kg/day 680 milligrams
20 mg/kg/day 1360 milligrams

 

So, yes, liver damage did occur but only when given extremely high dosages of CBD daily. And almost all the liver enzyme levels returned to normal upon stopping the drug or reducing the daily dosage.

When purchasing CBD in a store or on the web, none of those retail outlets will ever sell you a CBD supplement with a daily serving anywhere close to the dosages in Epidiolex.

As always, too much of a good thing can be bad for you. However, if you take reasonable doses and follow the recommended serving amounts on over-the-counter CBD, you and your liver should be safe to enjoy CBD’s many health benefits.

And, don’t forget, in the Epidiolex study, for those whose liver issues did not normalize at the dosage they were given, the remainder of liver issues were resolved by discontinuation of Epidiolex or reduction in Epidiolex dosage.

5 Studies Supporting CBD for Liver Health

Numerous studies prove that CBD is helpful in reducing pain and inflammation, both of which benefit a liver patient.

Below are 5 studies that support people who suffer from various forms of liver disease.

1. Mechanistic Potential and Therapeutic Implications of Cannabinoids in Nonalcoholic Fatty Liver Disease.

It was shown that CBD, the endocannabinoid system and its associated cannabinoid have demonstrated promising effects with respect to increased resistance to hepatic steatosis, and reversal of hepatic steatosis.

2. Potential of Cannabidiol for the Treatment of Viral Hepatitis

Preliminary screening of cannabidiol (CBD) revealed that CBD is active against HCV in vitro. CBD inhibited HCV replication by 86.4% at a single concentration of 10 μM with EC50 of 3.163 μM in a dose-response assay. These findings suggest that CBD could be further developed and used therapeutically against HCV.

3. Marijuana is not associated with progression of hepatic fibrosis in liver disease: a systematic review and meta-analysis.

Nine studies with 5, 976, 026 patients were included in this meta-analysis. Prevalence of hepatic fibrosis was evaluated in nonalcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis C and HIV coinfection.

CONCLUSION: Marijuana use did not increase the prevalence or progression of hepatic fibrosis in HCV and HCV/HIV-coinfected patients. In fact, to the contrary, they noted a reduction in the prevalence of NAFLD in marijuana users.

4. Two non-psychoactive cannabinoids reduce intracellular lipid levels and inhibit hepatosteatosis.

Obesity and associated metabolic syndrome have quickly become a pandemic and a major detriment to global human health. The presence of non-alcoholic fatty liver disease in obesity has been linked to the worsening of the metabolic syndrome, including the development of insulin resistance and cardiovascular disease.

The effects of THC and CBD on lipid levels were examined in a variety of in vitro and in vivo systems, with special emphasis on models of hepatosteatosis.

RESULTS: THC and CBD directly reduce accumulated lipid levels in vitro in a hepatosteatosis model and adipocytes. Nuclear magnetic resonance-based metabolomics confirmed these results and further identified specific metabolic changes in THC and CBD-treated hepatocytes.

CONCLUSIONS: These results suggest that THC and CBD might be used as new therapeutic agents for the pharmacological treatment of obesity- and metabolic syndrome-related NAFLD/hepatosteatosis.

5. The endocannabinoid system and liver diseases.

The Endocannabinoid System (ECS) is highly up-regulated during chronic liver diseases and, to date, it has been implicated in the pathogenesis of non-alcoholic fatty liver disease, progression of fibrosis to cirrhosis, and the development of the cardiovascular abnormalities of cirrhosis, such as the hyperdynamic circulatory syndrome and cirrhotic cardiomiopathy.

Furthermore, the ECS influences the mechanisms responsible for cell damage and the inflammatory response during acute liver injury, such as that resulting from ischaemia-reperfusion.

By taking CBD, it triggers the CB(1) and CB(2) receptors of the ECS. At present, the CB(1) receptor represent the most attractive pharmaceutical tool to resolve fat accumulation in patients with non-alcoholic fatty liver disease and to treat patients with cirrhosis, as they may slow the progression of fibrosis and attenuate the cardiovascular alterations associated with the advanced stage of the disease.

CBD Has Minimal Side Effects

In fact, across most studies, CBD has shown to have considerably minimal side effects. In numerous studies testing CBD on human epilepsy patients, research found the most common side effects are:

    • tiredness
    • diarrhea
    • and changes of appetite/weight.

Compared to other drugs that have also been tested on epilepsy patients, CBD has been found to have a better side effects profile. The one conclusion across all of these studies, though, is that more research needs to be done before we can have a true understanding of CBD’s effects on the human liver and the body in general.

Choosing the Right CBD Supplement

If you are looking to purchasing CBD to treat we recommend you should ask yourself these 4 questions as you shop.

1. Do you want a vape, tincture, cream or pill?

  • Vapes and tinctures are the most effective and quickest forms. They quickly get absorbed into your bloodstream and can get utilized by your body the fastest.
  • Creams are recommended for pain and are the best for being able to directly target the area causing your pain.
  • Pills are the least effective, since they have to go through your stomach, take longer to work and part of their benefit can be destroyed while being digested by your body.

2. Does the CBD bottle have a supplement facts panel?

For a CBD in liquid form, make sure the bottle has supplemental information right on the label in the form of a supplement facts panel.

For a cream, make sure CBD is listed in the ingredients list. In both cases, make sure it clearly tells you how much CBD is in the container.

3. Do you want to use CBD isolate or full spectrum?

  1. CBD Isolate is pure canabidiol that has no THC or terpenes in it. It will not give you the high associated with cannabis, but will provide you with the medical benefits of CBD.
  2. Full Spectrum CBD will have trace amounts of THC and terpenes in it, up to .03%. This will provide what is known as the “entourage effect,” giving you a bit of a high.

4. Where was the CBD derived and manufactured?

To ensure quality and safety, we recommend you purchase CBD which is:

  • 100% USA-grown, non-GMO industrial hemp
  • Manufactured in an FDA-Registered facility maintaining cGMP compliance and food certified
  • 3rd-party lab tested for purity and potency, ensuring what is on the label is what’s inside each bottle

Natural Wellness’ THC-Free CBD Products meet all our suggested guidelines.

Natural Wellness's THC-Free Hemp Oil is safe for your liver.

All their CBD products are derived from 100% USA-grown, non-GMO industrial hemp, manufactured in an FDA-Registered facility maintaining cGMP compliance and food certification. They are then 3rd-party tested for purity and potency ensuring that you get what you pay for. All their products also meet FDA label specifications and tell you the amount of CBD in each serving and container.

If you are looking for the best option, Natural Wellness is your answer.

Adams, M. (2019, June 18). Marijuana Study Finds CBD Can Cause Liver Damage. Retrieved July 03, 2019, from https://www.forbes.com/sites/mikeadams/2019/06/18/marijuana-study-finds-cbd-can-cause-liver-damage/

Caraceni, P., Domenicali, M., & Bernardi, M. (2008). The Endocannabinoid System and Liver Diseases. Journal of Neuroendocrinology, 20(S1), 47-52. doi:10.1111/j.1365-2826.2008.01679.x

Citroner, G. (2019, April 15). Marijuana May Protect the Liver from Alcohol, But Experts Urge Caution. Retrieved July 08, 2019, from https://www.healthline.com/health-news/marijuana-may-protect-the-liver-from-alcohol-but-experts-urge-caution#How-does-cannabis-prevent-ALD

Dibba, P., Li, A., Cholankeril, G., Iqbal, U., Gadiparthi, C., Khan, M., . . . Ahmed, A. (2018). Mechanistic Potential and Therapeutic Implications of Cannabinoids in Nonalcoholic Fatty Liver Disease. Medicines, 5(2), 47. doi:10.3390/medicines5020047

Farooqui, M. T., Khan, M. A., Cholankeril, G., Khan, Z., Abdul, M. K., Li, A. A., . . . Ahmed, A. (2019). Marijuana is not associated with progression of hepatic fibrosis in liver disease. European Journal of Gastroenterology & Hepatology, 31(2), 149-156. doi:10.1097/meg.0000000000001263

Highlights of Prescribing Information. (2018, June). Retrieved July 03, 2019, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

Iffland, K., & Grotenhermen, F. (2017). An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis and Cannabinoid Research, 2(1), 139-154. doi:10.1089/can.2016.0034

Silvestri, C., Paris, D., Martella, A., Melck, D., Guadagnino, I., Cawthorne, M., . . . Marzo, V. D. (2015). Two non-psychoactive cannabinoids reduce intracellular lipid levels and inhibit hepatosteatosis. Journal of Hepatology, 62(6), 1382-1390. doi:10.1016/j.jhep.2015.01.001

Toyang, N., Lowe, H. C., & Mclaughlin, W. (2017). Potential of cannabidiol for the treatment of viral hepatitis. Pharmacognosy Research, 9(1), 116. doi:10.4103/0974-8490.199780

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About the Author

Stephen Holt, MD, PhD, FACP

Stephen Holt, M.D. is a Distinguished Professor of Medicine NYCPM (Emerite) and a medical practitioner in New York State. He has published many peer-review papers in medicine and he is a best-selling author with more than twenty books in national and international distribution. He has received many awards for teaching and research. Dr. Holt is a frequent lecturer at scientific meetings and healthcare facilities throughout the world. He is a best selling author and the founder of the Holt Institute of Medicine.

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