CBD And Liver Toxicity
While the World Health Organization has stated in its 2018 critical review report that CBD is generally well-tolerated by the human body and non-addictive, one 2019 study on CBD and liver toxicity from the University of Arkansas found that, at large doses, CBD caused hepatotoxicity on mice. So, is CBD safe for your liver or not?
With increasing numbers of countries legalizing the consumption of CBD, more research is underway about its possible effects on the body. The 2019 study was one of them. Its publication caused concern among people who were already consuming CBD as they feared it could damage their liver.
CBD is metabolized by the liver through enzymes, so the study conducted by the University of Arkansas aimed at systematically analysing its effects on the liver. However, critics immediately pointed out a number of problems with the study, including the huge amounts of CBD administered on the mice.
Topics in this article:
How does CBD work in the body?
The connection between CBD and the liver
The University of Arkansas study
So, is CBD dangerous for your liver or not? To answer that question, we first need to understand how CBD enters the body and what its effects are.
How does CBD work in the body?
The human body contains the endocannabinoid system (ECS), which regulates many bodily functions such as appetite, mood, reproduction, inflammation, pain perception, motor perception, and even temperature perception. The role of the ECS is to keep our body in balance with all systems working properly and in harmony with each other.
The ECS took its name because it uses a family of lipid neurotransmitters called cannabinoids. When they are produced by the body, they are called endocannabinoids.
Cannabinoids are also found in hemp and other plants. These are called phytocannabinoids. These have subtle chemical differences to endocannabinoids but also great similarities.
Our ECS utilizes two endocannabinoids, called anandamide and 2-AG. When the ECS is triggered, it releases these to attach to their relevant receptors, CB1 and CB2.
Research has shown that CBD has a great affinity with the cannabinoid 2-AG. When consumed, CBD seems to help the body make better use of its own cannabinoids, thus assisting the ECS in restoring the body’s homeostasis—its natural harmony and balance. By gently nudging our endocannabinoids to be more efficient, CBD may help keep our bodies in physical and mental equilibrium.
The connection between CBD and the liver
How is CBD metabolized?
When CBD is consumed orally, it is absorbed by the digestive system. After reaching the stomach, it travels into the liver where it is metabolized by enzymes. Once CBD is metabolized, it enters the blood circulation. Only then does it act on the body.
When CBD reaches the liver, it monopolizes the enzymes necessary for its metabolism at the expense of other compounds. This is called the “first-pass effect.”
Most researchers studying CBD and liver toxicity focus on the cytochrome enzyme CYP450. This is the enzyme that metabolizes, among others, more than 60% of medicines.
What is the liver enzyme CYP450?
Upon CBD reaching the liver, CYP450 focuses on it and largely ignores any other compounds, including drugs. This is the reason why CBD interacts with several drugs and medicines, including blood-thinners, antidepressants, some antibiotics, some thyroid medications, and heart medication.
To metabolize CBD, the body uses up most of its CYP450 enzymes, leaving little behind for other medicines and drugs. CBD behaves as a competitive inhibitor and prevents chemical compounds from common medicines from being metabolized. As a result, they linger in the body longer than they should, potentially leading to liver damage and fatty liver.
For example, if CBD makes it more difficult for your body to metabolize your usual heart medication, the lingering compounds of the medicine could, in theory, build up into fatty acids and damage the liver.
More research is needed to determine if this risk is only theoretical. A 2016 study studying just this kind of interactions, reported that:
“The drug-drug interactions between cannabinoids and various drugs at the CYP level are reported, but their clinical relevance remains unclear. The direct activation/inhibition of nuclear receptors in the liver cells by cannabinoids may result in a change of CYP expression and activity.”
What affects CBD’s binding to the CYP450 enzyme?
It is still unclear how fast and how firmly CBD binds to the CYP450 enzymes. It is generally thought that this depends on several factors, including:
- The quantity of CBD consumed;
- whether it was isolate CBD or full-spectrum CBD;
- the frequency of CBD use;
- the metabolism and general health of the individual.
More research is required to understand how and why CBD reaches the CYP450 enzymes first and whether there is a way to make it less competitive towards other medicine. There is ongoing research about the activation and inactivation of the CYP450 enzymes and the inter-toxicities between drugs and/or CBD.
Researchers need to establish which drugs interact with each other and which ones displace CYP450 at the expense of the rest. Similar studies need to be performed with CBD and liver medicines.
What does the liver do?
The major role of the liver is to clean the blood from impurities and keep its chemical levels in balance. Picture the liver as the vacuum cleaner of our blood, cleaning it from waste and potentially harmful substances.
When we eat, our digestive system pushes the blood to the liver. The liver then refines the blood, keeping useful nutrients and discarding unnecessary ones.
Similarly, the liver metabolizes any drugs that have been ingested in the same way: the medicine is ingested and reaches the stomach. The blood from the stomach is processed by the liver, which metabolizes the medicine and uses it as intended.
Apart from metabolizing food and medicine, the liver is also tasked with regulating fats throughout the body as well as amino acids for protein production. The liver also handles haemoglobin to build and store iron and keeps the blood in balance when it comes to blood clotting.
All in all, a healthy liver is essential for a healthy life. Any liver damage can affect a whole range of organs, disrupting sensitive balances and leading to health problems and disequilibrium.
It’s no wonder, then, that researchers have focused on CBD and liver toxicity.
The University of Arkansas study
The 2019 study by the University of Arkansas examined how large doses of CBD affected mice livers. They administered single doses of 246, 738, and 2,460 mg/kg of CBD to mice.
The study also looked at repeated but smaller doses of CBD and how they affected the mice livers. In this case, they administered 61.5, 184.5, and 615 mg/kg of CBD over a period of 10 days.
When the mice took the maximum dose of 2,460mg/kg they displayed liver toxicity, swelling, and damage. Mice showed sub-lethargic behaviour, loss of appetite, and elevated liver enzymes levels (AST and ALT).
Those taking a single CBD dose but lower than the 2,460mg/kg showed smaller but visible increases in the liver enzymes.
Mice taking the daily high dose also displayed liver toxicity and high enzyme levels. However, the mice taking the daily lower doses did not display any liver toxicity.
The findings of the study can be summarized as follows:
- The highest CBD dose resulted in high liver toxicity.
- A single administration of lower doses only caused increases in liver-to-body weight ratios.
- Doses of more than 50mg/kg, although well tolerated after a single administration, were toxic when repetitively delivered.
Interpreting the University of Arkansas study
The study showed that CBD has an impact on the mice liver, particularly at increased doses. More research is required to better understand the interplay between CBD and liver enzymes.
However, the study administered immense quantities of CBD to the mice, far beyond what a human might consume. Although there is no recommended daily allowance for CBD, the quantities given to the mice were not representative of any human use.
The FSA CBD guidelines recommend a top dose of 70mg a day. The lowest single dose the researchers gave the mice was 246 mg per kilo. This is equivalent to an 80-kg human consuming a whopping 19,680 mg of CBD. Even worse, the highest dose is ten times that: an 80-kg human would have to consume 191 grams of pure CBD—the equivalent of drinking almost 4 litres of 5% CBD oil in a single day.
All drugs and even some natural remedies become toxic when used in large enough quantities, including over-the-counter painkillers. Even water can kill you: in one notorious case, a 28-year-old California woman died after competing in a radio station’s on-air water-drinking contest. After downing six litres of water in three hours, she developed water intoxication—brain swelling that manifests as seizures, coma, respiratory arrest, brain stem herniation, and death.
Other problems with the study
Another problem with the study is that it used CBD isolate. Full-spectrum CBD contains all the cannabinoids found in hemp, including CBD, THC, CBC, CBG, and CBN, as well as terpenes, flavonoids, and fatty acids. Research suggests that taking full-spectrum CBD has different effects on the body compared to taking CBD isolate.
So, the study demonstrated that CBD can cause liver toxicity when taken in insane amounts, either as a one-off or over a longer timeframe. However, taking large enough amounts of even common over-the-counter drugs like ibuprofen or paracetamol also causes liver toxicity and other health problems. Even so, millions of people take these every day without experiencing any hepatotoxicity or health issue.
Apart from dosage, it is helpful to remember that the quality of the CBD consumed is also crucial to our health.
Why CBD quality matters
Mislabelling CBD products
A common problem with CBD is a lack of monitoring. This has led to mislabelling. Studies found that the content of CBD and other cannabinoids in many products differed from what was stated on the label. A 2019 report on the CBD market in the UK found that 38% of the tested products had less than 50% of the advertised CBD content. And one product from a high-street shop contained no CBD whatsoever!
Also, some CBD products contained more than the 0.2% of THC that is the legal threshold in the UK. This could be a problem for people being tested for drugs at work.
CBD products with heavy metals and pesticides
Worryingly, many CBD products contain heavy metals and pesticides above food limit safety levels.
Traces of heavy metals and pesticides are cleaned from the blood in the liver. Accumulating such harmful substances in our blood could lead to our liver overworking to clean the blood. It can also lead to liver damage if the harmful substances are consumed over a long time period and tiny particles start building up inside the liver itself.
The reason why CBD products might contain heavy metals and pesticides is that hemp is a bio-remediation plant. This means it has a useful ability to clean soils from heavy metals, pesticides, and herbicides with its deep roots.
Many farmers use hemp plants to clean their soils before planting their crops. Because hemp grows fast, this is a quick and effective way to clean soils. However, this is non-desirable for hemp products.
How can you choose high-quality CBD?
In order to make sure the CBD you consume is pure, clean, and properly labelled, you need to research your CBD producer and manufacturer.
Reputable producer
You must choose a reputable, experienced, and trustworthy producer who doesn’t cut corners. Look around, ask friends and relatives, and research online CBD producers who manufacture high-quality CBD products.
Small details like the CBD coming in glass jars instead of plastic ones and the overall presentation of a manufacturer can tell you a lot about the quality and dedication this producer exhibits with regards to the production of CBD products.
No extravagant claims
There is no scientific proof as yet that CBD works for specific health conditions. CBD has only been approved as an NHS-approved medicine for two rare forms of epilepsy in children. Apart from that, CBD has shown some interesting preliminary evidence regarding its potential as an anti-inflammatory, anti-depressant, and anti-anxiety among other things, but further large-scale research is needed.
Therefore, right now CBD is considered a natural supplement consumed by healthy individuals to support their overall health.
If you see a CBD manufacturer claiming that their products cure hundreds of illnesses and chronic conditions, it is best to refrain from buying from this producer. Such claims are extravagant and could push people to substitute their prescribed medication for CBD, thus jeopardizing their health.
CoA
Many CBD producers display their Certificates of Analysis (CoA) publicly, usually on their website. Every batch can be traced and checked for heavy metals, CBD content—as well as THC content and other cannabinoids—pesticides, and various compounds.
The display of such a certificate from a third-party lab means that the producer is testing and checking their products, ideally throughout the production process. This suggests a thorough and consistent testing regime you can trust.
The CoA will also give the exact content of CBD in the product you will be consuming. You will be better able to gauge how much CBD you will be taking and how this could impact your health.
Organic
Because hemp can be used as a bio-remediation plant, sticking to organic hemp may be better for your health. Organic hemp ensures that your CBD product contains no heavy metals or pesticides and is not going to put extra pressure on your liver.
However, not having an organic certificate doesn’t necessarily imply a polluted product. Organic certification can be tricky to obtain and many CBD producers of excellent products are unable to get certified.
CBD intake: dosage and method
The CBD dosage that was administered to the mice was enormous by any standards.
But what is the right CBD dosage for you? There is no recommended daily allowance or NHS guidelines, so CBD dosage can be tricky. The usual advice is to “start low, go slow.” Start with a low CBD dosage and increase it incrementally until you have reached the intended effect.
What is an average CBD dosage?
It is usually accepted that a normal low dosage is between 5 and 15 mg per day, depending on your age, weight, metabolism, exercise levels, and general health condition.
What we do know about the liver and how it processes food and substances is that smaller doses are easier to handle than larger ones. The liver’s role is to clean the blood, therefore consuming normal quantities of CBD lets it do its job in a natural and unforced way. When quantities are extraordinarily large, the liver will process the quantity it can manage and discard the rest without processing it.
When it comes to the liver and CBD dosage, lower but more frequent doses may be better and more manageable than a single high one.
Micro-dosing and CBD
This has led some to suggest that micro-dosing CBD could be more effective for the body and healthier for the liver.
Microdosing involves taking multiple small quantities of CBD throughout the day rather than one large one.
Microdosing maintains a steady and consistent level of CBD in the blood. Also, the liver is not required to process a large quantity of CBD in a single instance.
Choose another method of CBD consumption
If you are concerned about ingesting CBD and its potential impact on your liver, you could choose other methods of consumption.
CBD topical creams
If you want to help your skin feel healthy or to assist with a painful joint, you could opt for a CBD topical cream. Although CBD bioavailability of topical products is low, around 5 to 10%, you could still benefit from its localized effect.
The skin is a challenging barrier to anything entering the body, whether this is a harmful substance or a therapeutic topical cream. Any CBD topical cream needs to cross all seven layers of skin before entering the bloodstream. With each layer, the topical cream loses part of its effectiveness, which is why only 5-10% manages to reach the bloodstream.
However, the use of a topical cream bypasses the digestive system and the liver and therefore does not burden the latter’s workload.
Vaping CBD
Another way to consume CBD is through inhalation. By inhaling your CBD with a vape pen, the CBD enters your lung capillaries and goes directly to the bloodstream, again bypassing the liver.
There are various ways to inhale CBD and you need to make sure you are using a vape juice specifically designed for inhaling.
Sublingual use
The last way to bypass the digestive tract and, ultimately, the liver, is CBD tinctures.
Tinctures are placed under the tongue where tongue capillaries are located. By keeping the CBD tincture there for 30 to 60 seconds, CBD enters the tongue capillaries and reaches the bloodstream directly through them, therefore circumventing the stomach.
More research is still needed
There is still a lot to discover about CBD and liver interaction. Just like many medicines and natural remedies, CBD is processed by the liver and the impact it can have on the liver is crucial for our general health.
The University of Arkansas study showed that huge quantities of CBD have a detrimental effect on the liver of mice. Research should now be performed on humans, focusing on long-term usage of normal and realistic quantities of CBD.
The consensus is that healthy people with a healthy liver can take normal quantities of CBD on a frequent basis. In addition, most conventional drugs also damage the liver. The same applies to alcohol.
Even so, it is best to discuss with your GP before experimenting with CBD to assess whether it might interact with any pre-existing condition or medication you are already taking. Your doctor will also evaluate your general health level and advise you on CBD dosage and frequency of use.
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