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Cannabidiol (CBD) and Liver Function: A Comprehensive Overview
Introduction to CBD and Liver Function
Cannabidiol (CBD), a non-psychoactive compound found in cannabis, has gained popularity for its potential therapeutic benefits. However, its effects on liver function have been a subject of debate and research. This article synthesizes findings from multiple studies to provide a clear understanding of how CBD interacts with the liver.
Pharmacokinetics of CBD and Liver Function
Variability in CBD Formulations
Research indicates significant pharmacokinetic variability between different commercial CBD formulations. This variability extends to CBD metabolites, which can influence the overall effect of CBD on the body1. Additionally, food intake can alter the pharmacokinetics of CBD, increasing its systemic availability1.
CBD and Liver Enzyme Levels
A phase I clinical trial involving healthy adults revealed that high doses of CBD (1,500 mg/day) could lead to elevations in serum alanine aminotransferase (ALT) levels, a marker for liver injury. Approximately 44% of participants experienced ALT levels above the upper limit of normal, with some cases meeting the criteria for drug-induced liver injury2. This suggests that while CBD is generally well-tolerated, high doses may pose a risk to liver health.
Protective Effects of CBD on Liver Conditions
Alcohol-Induced Liver Injury
CBD has shown promise in protecting against liver injuries induced by chronic alcohol consumption. Studies on mice have demonstrated that CBD can reduce serum transaminase levels, hepatic inflammation, oxidative stress, and fat accumulation in the liver5. These findings suggest that CBD may have therapeutic potential for treating alcoholic liver diseases.
Non-Alcoholic Fatty Liver Disease (NAFLD)
CBD has also been found to alleviate liver injuries in models of non-alcoholic fatty liver disease (NAFLD). In mice fed a high-fat, high-cholesterol diet, CBD treatment reduced liver steatosis, oxidative stress, and inflammation by inhibiting the NF-κB and NLRP3 inflammasome pathways3 7. These anti-inflammatory and antioxidative properties highlight CBD's potential in managing NAFLD.
Hepatic Ischemia/Reperfusion Injury
In cases of hepatic ischemia/reperfusion injury, a common issue during liver transplantation, CBD has been shown to reduce inflammation, oxidative stress, and cell death. These protective effects were observed even in the absence of classical cannabinoid receptors, suggesting a unique mechanism of action10.
Safety and Dosage Considerations
Impact of Hepatic Impairment
A study on the pharmacokinetics of CBD in individuals with varying degrees of hepatic impairment found that those with moderate to severe impairment had significantly higher CBD exposure. This indicates the need for dose adjustments in patients with liver conditions to avoid potential toxicity6.
Long-Term Use and Liver Architecture
Long-term use of CBD, even at high doses, did not show toxic effects on liver architecture in experimental rat models. This suggests that CBD, when used appropriately, may not cause structural damage to the liver9.
Conclusion
The interaction between CBD and liver function is complex and influenced by various factors, including dosage, formulation, and individual liver health. While high doses of CBD can lead to liver enzyme elevations, moderate use appears to offer protective benefits against various liver conditions. Clinicians should consider these findings when recommending CBD, especially for patients with pre-existing liver conditions. Further research is needed to fully understand the long-term effects of CBD on liver health.
Sources and full results
Most relevant research papers on this topic
Cannabidiol and Cannabidiol Metabolites: Pharmacokinetics, Interaction with Food, and Influence on Liver Function
CBD formulations vary in pharmacokinetics, but low-dose CBD does not pose a risk to normal liver function, and consuming CBD with food alters its metabolism and systemic availability.
RCT
Very Rigorous JournalCannabidiol and Abnormal Liver Chemistries in Healthy Adults: Results of a Phase I Clinical Trial
Healthy adults consuming CBD may experience elevations in serum ALT consistent with drug-induced liver injury, highlighting the need for clinicians to be aware of this potential effect.
RCT
Rigorous JournalCBD Alleviates Liver Injuries in Alcoholics With High-Fat High-Cholesterol Diet Through Regulating NLRP3 Inflammasome–Pyroptosis Pathway
CBD can alleviate liver injuries in heavy alcohol drinkers by regulating inflammation through the NLRP3 inflammasome-pyroptosis pathway.
Non-RCT
Animal StudyThe Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver Disease
Abn-CBD reduces inflammation and protects liver, pancreas, and adipose tissue in obese mice with non-alcoholic fatty liver disease, potentially offering novel pharmacological strategies for managing obesity-related metabolic disorders.
Non-RCTAnimal StudyCannabidiol attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation and neutrophil-mediated injury
CBD shows potential in treating alcohol-induced liver diseases associated with inflammation, oxidative stress, and steatosis, warranting further exploration in human trials.
Non-RCTAnimal Study
Highly CitedA Phase 1, Open‐Label, Parallel‐Group, Single‐Dose Trial of the Pharmacokinetics and Safety of Cannabidiol (CBD) in Subjects With Mild to Severe Hepatic Impairment
CBD is well-tolerated and well-tolerated in patients with mild to severe hepatic impairment, but dose modification is necessary based on benefit-risk considerations.
Rigorous JournalHighly CitedCannabidiol protects livers against nonalcoholic steatohepatitis induced by high‐fat high cholesterol diet via regulating NF‐κB and NLRP3 inflammasome pathway
CBD protects livers against nonalcoholic steatohepatitis induced by a high-fat, high cholesterol diet by suppressing NLRP3 inflammasome activation through deactivation of NFB in macrophages.
Non-RCTAnimal StudyCannabidiol (CBD) Dosing: Plasma Pharmacokinetics and Effects on Accumulation in Skeletal Muscle, Liver and Adipose Tissue
Oral CBD consumption in rats leads to significant accumulation in adipose tissue, with gender-specific effects influencing pharmacokinetics and tissue accumulation.
Very Rigorous JournalMICROSCOPIC ARCHITECTURE OF THE LIVER OF EXPERIMENTAL RATS AFTER CANNABIDIOL OIL APPLICATIONS
CBD oil use as a dietary supplement did not cause toxic effects on the liver or cause any damage in experimental rats.
Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death
CBD protects against hepatic ischemia/reperfusion injury by reducing inflammation, oxidative/nitrative stress, and cell death, independent of classical CB1/2 receptors.
Non-RCTAnimal StudyHighly Cited