The liver is the body’s central chemical processing plant, responsible for filtering blood and metabolizing nearly every substance consumed, including compounds from the cannabis plant. The two most studied cannabinoids are delta-9-tetrahydrocannabinol (THC), which causes psychoactive effects, and cannabidiol (CBD), which is non-intoxicating. Since the liver is the primary site where these compounds are broken down, any health effects or interactions from cannabis use are linked to this organ’s function. Research into cannabis and liver health is ongoing, revealing potential risks mainly at high doses, alongside emerging evidence of therapeutic benefits.
How the Liver Processes Cannabinoids
The liver processes cannabinoids through a specialized system of enzymes known as Cytochrome P450 (CYP450), which works to transform fat-soluble compounds into water-soluble metabolites for excretion. When cannabis is consumed orally, it undergoes extensive first-pass metabolism, meaning a significant portion is processed by the liver before entering the bloodstream. This process is why edibles often produce effects that are stronger and last longer than inhaled cannabis.
THC is primarily metabolized by the CYP2C9, CYP2C19, and CYP3A4 enzymes. These enzymes first convert THC into 11-hydroxy-THC (11-OH-THC), which is itself psychoactive and often more potent than the parent compound. This metabolite is then further broken down into the inactive, water-soluble 11-carboxy-THC (11-COOH-THC), which is eventually eliminated from the body.
CBD also relies on the CYP450 system, mainly involving the CYP3A4 and CYP2C19 enzymes for its breakdown. The primary metabolite of CBD is 7-hydroxy-CBD (7-OH-CBD), which is then processed further for elimination. Because both THC and CBD utilize the same metabolic enzymes, consuming either cannabinoid can influence the body’s ability to process other substances that rely on these pathways.
Known Risks of Liver Injury
While moderate use of traditional cannabis is not associated with severe liver damage in healthy individuals, certain products carry risks of hepatotoxicity. The most significant concern arises from the use of high-dose CBD products, particularly the pharmaceutical grade used in clinical trials. Studies show that daily CBD doses of 1,000 milligrams or more are associated with elevated liver enzymes, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
These elevated enzyme levels are a marker of stress or injury to the liver cells, an effect that is dose-dependent and reversible upon discontinuing use. The risk of drug-induced liver injury (DILI) is heightened when high-dose CBD is co-administered with other medications known to stress the liver, such as the anti-epileptic drug valproate. Pre-existing liver conditions, such as chronic hepatitis C, may also increase vulnerability, with some studies linking daily cannabis use in these patients to accelerated fibrosis progression.
Consumption of synthetic cannabinoids, often sold illicitly and chemically distinct from plant-derived THC and CBD, is another risk factor. These unregulated compounds are potent and have been linked to severe toxicity, including acute liver failure, due to the metabolic burden on the liver. Consumers of commercially available CBD products must also be aware of product quality, as contamination with unlisted compounds or other toxins can lead to unexpected adverse effects.
Potential Protective and Therapeutic Roles
Despite the risks associated with high doses, research suggests that certain cannabinoids may possess properties that could protect the liver from chronic disease. Cannabidiol (CBD) has demonstrated anti-inflammatory and antioxidant activities in preclinical models. These properties are relevant for conditions like Non-Alcoholic Fatty Liver Disease (NAFLD) and alcohol-associated liver disease (ALD), which are driven by chronic inflammation and oxidative stress.
In animal models of liver injury, CBD has been shown to reduce both steatosis (fat accumulation) and inflammation by blocking cellular pathways. Certain cannabinoid precursors, such as delta-9-tetrahydrocannabinolic acid (\(\Delta^9\)-THCA), have also been found to attenuate liver fibrosis and inflammation in mice models of NAFLD. The mechanism is thought to involve the modulation of the endocannabinoid system, which becomes active during liver disease progression, helping to regulate immune and fibrotic responses.
These findings indicate that cannabinoids may hold promise for managing chronic liver conditions. However, most evidence comes from cell cultures and animal studies, often involving pure compounds at specific dosages. Further human investigation is needed to determine the clinical effectiveness and safety profile of cannabinoids as a therapeutic option for liver diseases.
Interactions with Other Medications
The liver’s CYP450 system is not only responsible for breaking down cannabinoids, but it also metabolizes approximately 70% of all prescription drugs. Cannabinoids, particularly CBD, can act as competitive inhibitors, monopolizing the CYP450 enzymes and slowing down the metabolism of other co-administered medications. This competition means that the concentration of the other drug remains higher in the bloodstream for a longer period, which can lead to increased side effects or toxicity.
An example of this is the interaction with warfarin, a common blood thinner metabolized by CYP2C9. When CBD is introduced, it inhibits CYP2C9, which can cause warfarin levels to rise, leading to an elevated International Normalized Ratio (INR) and an increased risk of severe bleeding. Similarly, co-administration of CBD with anti-seizure medications like clobazam can lead to increased clobazam levels and enhanced sedation due to the inhibition of CYP2C19.
Other drug classes that rely on the affected CYP450 enzymes include antidepressants, immunosuppressants, and chemotherapy agents. Healthcare providers must be aware of any concurrent cannabinoid use to carefully monitor drug levels and adjust dosages to prevent harmful interactions.