Cannabis Use in Hepatic Disease
Dr. Andre discusses the use of Cannabis in hepatic disease or in patients with elevated liver enzymes.
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Safety Considerations in Cannabis Medicine
As the fields of endocannabinoid system (ECS) science and Cannabis medicine develops, veterinary practitioners are learning how to guide the use of this medicine in our animal patients. The molecules produced by the Cannabis plant offer practitioners multiple, unique treatment options to offer their patients. However, the scientific and medical communities are still learning about how to best utilize these molecules as well as what monitoring parameters need to be in place to protect our patients from harm.
The most commonly reported adverse side effects from Cannabis use in dogs and cats are liver enzyme elevation and mild GI upset.
The most commonly reported adverse side effects from Cannabis use in dogs and cats are liver enzyme elevation and mild GI upset.
Evaluating Hepatic Health
There are several ways that clinicians are able to monitor the hepatic (liver) health of a patient.
Chemistry panel
These values may be used to evaluate hepatic health:
It is not uncommon to see liver enzyme elevation when a patient is placed on a cannabis product…particularly the CBD-dominant products. Our current understanding of this clinical result is that cannabinoids, particularly CBD, have interactions with a hepatic enzyme complex called cytochrome p450. Although our understanding of this mechanism may develop in the future, medical practitioners currently believe that the metabolism of CBD (as well as other cannabinoids) require this enzyme to function at a higher level. As a result, this enzyme complex takes up extra space in its containing cell - think about a bodybuilder who bulks up after lots of workouts! As the liver cell is stretching to accommodate its new, bulky occupants, the ALP enzyme can escape out of the cell into the blood to then be detected in the blood serum on a chemistry panel.
It’s important to recognize that an ALP elevation is not synonymous with liver cell injury. It is more of an identifying “flag” that tells us that there is some mechanism occurring in these liver cells that bears watching. ALP is a value that is also frequently elevated with the use of pharmaceuticals such as steroids, anti-seizure medications as well as extra-hepatic (outside the liver) causes such as bone damage or repair, GI disease, dental disease, renal (kidney) disease and others. Because the liver is the filter for all of the body…many other processes can affect liver values. Again, this is why an ALP elevation tells us to “pay attention” and is not automatically a sign of a severe issue or developing condition.
Bile acid assay
Bile acids are secreted by the liver and aid in the digestion of food. After working to break food down into more digestible parts, the bile acids are absorbed by the intestines, into the bloodstream, and recycled back into the liver. Some of the bile acids remain in the intestines and are lost in the feces.
A healthy, functioning liver will do a good job of filtering bile acids out of the bloodstream and be able to reuse the majority of these molecules. A less healthy liver will do a poor job of recycling the bile acids and a higher number will remain in the bloodstream.
A bile acid assay or test will evaluate the functional health of the liver and whether the liver able to do its job well. By evaluating the efficiency of the liver at recycling bile acids, we can gain a clinical picture of overall liver efficiency and function.
Abdominal ultrasound
In addition to evaluating the functional health of the liver, practitioners may also recommend a structural evaluation of this important organ. An abdominal ultrasound enables practitioners to gain a visual assessment of the liver. Problems such as hepatic or biliary (gallbladder) inflammation, neoplasia (cancer) and other structural abnormalities can be identified.
Chemistry panel
These values may be used to evaluate hepatic health:
- Alkaline phosphatase (ALP)
- Alanine transaminase (ALT)
- Aspartate transaminase (AST)
- Gamma-glutamyl transpeptidase (GGT)
It is not uncommon to see liver enzyme elevation when a patient is placed on a cannabis product…particularly the CBD-dominant products. Our current understanding of this clinical result is that cannabinoids, particularly CBD, have interactions with a hepatic enzyme complex called cytochrome p450. Although our understanding of this mechanism may develop in the future, medical practitioners currently believe that the metabolism of CBD (as well as other cannabinoids) require this enzyme to function at a higher level. As a result, this enzyme complex takes up extra space in its containing cell - think about a bodybuilder who bulks up after lots of workouts! As the liver cell is stretching to accommodate its new, bulky occupants, the ALP enzyme can escape out of the cell into the blood to then be detected in the blood serum on a chemistry panel.
It’s important to recognize that an ALP elevation is not synonymous with liver cell injury. It is more of an identifying “flag” that tells us that there is some mechanism occurring in these liver cells that bears watching. ALP is a value that is also frequently elevated with the use of pharmaceuticals such as steroids, anti-seizure medications as well as extra-hepatic (outside the liver) causes such as bone damage or repair, GI disease, dental disease, renal (kidney) disease and others. Because the liver is the filter for all of the body…many other processes can affect liver values. Again, this is why an ALP elevation tells us to “pay attention” and is not automatically a sign of a severe issue or developing condition.
Bile acid assay
Bile acids are secreted by the liver and aid in the digestion of food. After working to break food down into more digestible parts, the bile acids are absorbed by the intestines, into the bloodstream, and recycled back into the liver. Some of the bile acids remain in the intestines and are lost in the feces.
A healthy, functioning liver will do a good job of filtering bile acids out of the bloodstream and be able to reuse the majority of these molecules. A less healthy liver will do a poor job of recycling the bile acids and a higher number will remain in the bloodstream.
A bile acid assay or test will evaluate the functional health of the liver and whether the liver able to do its job well. By evaluating the efficiency of the liver at recycling bile acids, we can gain a clinical picture of overall liver efficiency and function.
Abdominal ultrasound
In addition to evaluating the functional health of the liver, practitioners may also recommend a structural evaluation of this important organ. An abdominal ultrasound enables practitioners to gain a visual assessment of the liver. Problems such as hepatic or biliary (gallbladder) inflammation, neoplasia (cancer) and other structural abnormalities can be identified.
Liver Health in Cannabis Patients
Because liver enzyme elevation is not uncommon in patients receiving a cannabis product, routine monitoring is important. Talk to your animal’s veterinary healthcare team about a monitoring plan prior to starting any animal on a cannabis product.
Running a baseline chemistry panel that includes ALP and ALT prior to starting a cannabis product will allow your veterinarian to identify any existing liver issues as well as track any changes that occur over time with Cannabis use.
Frequently, when the appropriate cannabis product is utilized in a patient that already has elevated liver values, we see a clinical improvement in these values. Cannabis provides strong inflammation control and, in many cases, the use of Cannabis results in improved liver values and an improved overall wellbeing of the patient.
Based on current research on the use of Cannabis in dogs, if the ALP levels are less than 2x the normal range of this enzyme, it is appropriate to continue the cannabis product administration and monitor these values over time. When ALP elevation has been identified in research animals, further evaluation (through a bile acid assay) has demonstrated that the liver was still functionally healthy. Currently, there is no evidence of short-term hepatotoxicity (liver damage) from the use of Cannabis.
If this value continues to increase, your animal’s health care team may recommend incorporating additional testing (such as a more comprehensive chemistry panel, a bile acid test or an abdominal ultrasound).
Running a baseline chemistry panel that includes ALP and ALT prior to starting a cannabis product will allow your veterinarian to identify any existing liver issues as well as track any changes that occur over time with Cannabis use.
Frequently, when the appropriate cannabis product is utilized in a patient that already has elevated liver values, we see a clinical improvement in these values. Cannabis provides strong inflammation control and, in many cases, the use of Cannabis results in improved liver values and an improved overall wellbeing of the patient.
Based on current research on the use of Cannabis in dogs, if the ALP levels are less than 2x the normal range of this enzyme, it is appropriate to continue the cannabis product administration and monitor these values over time. When ALP elevation has been identified in research animals, further evaluation (through a bile acid assay) has demonstrated that the liver was still functionally healthy. Currently, there is no evidence of short-term hepatotoxicity (liver damage) from the use of Cannabis.
If this value continues to increase, your animal’s health care team may recommend incorporating additional testing (such as a more comprehensive chemistry panel, a bile acid test or an abdominal ultrasound).
Monitoring guidance for elevated liver values
There is no “one-size-fits-all” plan for monitoring a patient that demonstrates elevated liver enzymes. It is important to work with your veterinary healthcare team to determine an individual plan for each patient and their unique condition(s).
Below are some basic guidelines for pet owners and their veterinary team members to consider:
Baseline assessment
Below are some basic guidelines for pet owners and their veterinary team members to consider:
Baseline assessment
- Full serum chemistry profile including ALP, ALT +/- GGT
- Complete blood count (CBC)
- Start a hepatic support supplement i.e. Denamarin, Standard Process’ Hepatic Support, milk thistle, etc.)
- +/- bile acid assay (if existing liver condition is present)
- +/- abdominal ultrasound (if existing liver condition is present)
- Serum chemistry profile including ALP, ALT +/- GGT
- Continue on a hepatic support supplement i.e. Denamarin, Standard Process’ Hepatic Support, milk thistle, etc.)
- Serum chemistry profile including ALP, ALT +/- GGT
- Continue on a hepatic support supplement i.e. Denamarin, Standard Process’ Hepatic Support, milk thistle, etc.)
- +/- bile acid assay (if liver values are still abnormal or increased)
- Continue to recheck every 3-6 months
- Continue on a hepatic support supplement i.e. Denamarin, Standard Process’ Hepatic Support, milk thistle, etc.)
- If liver function is within normal limits and no signs of clinical disease (icterus, nausea, inappetence), okay to continue cannabis therapy with continued monitoring
- +/- abdominal ultrasound
