The liver is a complex organ performing numerous functions, including processing nutrients, producing bile, and detoxifying harmful substances. Given its extensive involvement in maintaining overall health, there is growing public interest in understanding how cannabis use might affect its function.
How the Liver Processes Cannabis
The liver is the primary site for metabolizing cannabinoids like tetrahydrocannabinol (THC) and cannabidiol (CBD). This process largely involves the cytochrome P450 (CYP450) enzyme family, which converts cannabinoids into metabolites for elimination.
THC, the main psychoactive component, is metabolized by CYP2C9, CYP2C19, and CYP3A4 enzymes in the liver. This forms 11-hydroxy-THC (11-OH-THC), an active metabolite, which is then oxidized to 11-nor-9-carboxy-THC (THC-COOH), an inactive form. Both are further processed by UDP-glucuronosyltransferase (UGT) enzymes, making them water-soluble for excretion.
CBD also undergoes extensive metabolism by the CYP450 system, primarily through hydroxylation. CYP2C9, CYP2C19, and CYP3A4 enzymes play significant roles, forming metabolites like 7-hydroxy-CBD (7-OH-CBD) and 7-carboxy-CBD (7-COOH-CBD). These metabolites, like those of THC, are then glucuronidated for elimination.
Cannabis Research and Liver Health
Research into cannabis and liver health is ongoing, suggesting both potential adverse effects and therapeutic benefits. For non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), some observational studies show an inverse association between cannabis use and NAFLD prevalence, suggesting a reduction among users. The endocannabinoid system, interacting with cannabinoids, is recognized for its role in metabolic disorders and liver homeostasis, potentially offering a target for NAFLD treatment.
For viral hepatitis, particularly Hepatitis C (HCV), findings are mixed. Earlier studies suggested cannabis could worsen liver fibrosis and steatosis in HCV patients. However, more recent studies, including a systematic review, found no association between cannabis use and increased hepatic fibrosis progression in HCV and HCV-HIV co-infected patients. Some research reported lower HCV-related cirrhosis, reduced health costs, and improved HCV virologic outcomes by enhancing patient adherence to antiviral treatment.
Regarding cirrhosis and liver fibrosis, some studies indicate heavy cannabis use might be associated with an increased risk, especially in individuals with pre-existing liver conditions. Elevated liver enzymes, indicating liver stress or damage, have been linked to chronic cannabis use.
Conversely, certain cannabinoids, particularly CBD, have demonstrated anti-inflammatory and anti-fibrotic properties in preliminary studies, reducing liver inflammation and fibrosis in animal models. This suggests potential protective effects, though more human studies are needed.
The potential for drug-induced liver injury (DILI) from cannabis is being investigated. Some clinical studies, particularly with high doses of CBD, have shown elevated liver enzymes, a marker of liver cell damage. One study found 5% of participants had greatly elevated aminotransferase levels, which normalized after stopping CBD. While rare, DILI has been reported with natural marijuana, and high oral CBD doses (exceeding 1000 mg daily) have been linked to a higher risk of liver injury.
Factors Influencing Liver Response
The liver’s response to cannabis is influenced by dosage, frequency, and consumption method. Higher doses and more frequent use may present different risks than occasional, low-dose use. For instance, very high oral CBD doses (over 1000 mg per day) are associated with a higher risk of liver toxicity.
Consumption methods affect how cannabinoids reach and are processed by the liver. Smoked or vaped cannabis leads to rapid absorption through the lungs and quicker effects. Edibles, however, undergo first-pass metabolism in the liver, resulting in different metabolite profiles and concentrations compared to inhalation.
Individual variability plays a role due to genetic factors and overall health. Genetic variations in cannabinoid metabolism enzymes (e.g., CYP450 system) influence how quickly the liver processes these compounds, affecting therapeutic outcomes and side effects. People with compromised liver function may process cannabinoids differently, leading to slower elimination and increased side effects.
Individuals with pre-existing liver conditions may be more vulnerable to adverse effects. For example, daily cannabis use in those with underlying liver disease, particularly hepatitis C, has been advised against due to concerns about fibrosis progression.
Concomitant medications are also a consideration, as cannabinoids can affect liver enzymes that metabolize many common drugs. This interaction can alter medication levels, potentially causing heightened side effects or reduced effectiveness.
Current Scientific Perspective
The current scientific understanding of cannabis and liver health is still developing. While some research points to potential benefits, such as anti-inflammatory and anti-fibrotic properties (especially for CBD), overall evidence for widespread safety remains incomplete, particularly in vulnerable populations or with heavy use. Studies show CBD can reduce liver inflammation and fibrosis in animal models, and some human observational studies suggest a lower prevalence of NAFLD among cannabis users.
However, potential risks exist, such as elevated liver enzymes with high CBD doses, suggesting liver stress or injury. The impact on conditions like viral hepatitis is conflicting, with some studies suggesting worsening fibrosis while others report no negative impact. Healthcare professionals advise caution and consultation, especially for individuals with pre-existing liver conditions or those taking other medications, given potential drug interactions. Ongoing research continues to explore these complex interactions.