Liver and CBD: what do clinical trials and pharmacovigilance really reveal?

Cannabidiol (CBD), a key component of medical cannabis, is generating increasing interest for its potential therapeutic effects. The growing number of clinical trials and the accumulation of pharmacovigilance data are prompting a better understanding of its safety profile, particularly its effect on the liver. What signals are emerging? How should we interpret the drug interactions and adverse effects reported in the scientific literature? Let’s explore the answers offered by recent research. What do we know about CBD metabolism in the liver? The liver plays a central role in the transformation of CBD after ingestion. Cannabinoids are metabolized there primarily via cytochrome P450 enzymes, a family of enzymes essential for the breakdown of chemical substances, including medications. This hepatic metabolism determines the bioavailability of cannabidiol and greatly influences its tolerability. In both animals and humans, clinical trials show that most CBD is converted by isoforms such as CYP3A4 or CYP2C19. These enzymes can become saturated, especially at high doses, which alters the elimination rate of cannabidiol and other molecules that utilize the same hepatic pathways. Some recent findings also highlight individual variability, particularly related to patient genetics. The liver metabolizes more than 90% of absorbed CBD. Interindividual differences depend on the patient’s enzyme profile. Several common medications share these same cytochromes. What adverse effects on the liver have been observed in clinical trials? The majority of clinical trials conducted on CBD show a very good liver safety profile at low to moderate doses. However, the administration of high concentrations, sometimes required for certain therapeutic effects, has raised several cases of Transient elevation of liver enzymes These elevations, often asymptomatic, are among the mainadverse effects monitored in scientific protocols. In the context of current research, it is also worth noting that new studies are highlighting the implications of CBD on the body particularly regarding its anti-inflammatory effects, its interaction with anxiety, and its anticancer potential. These increases mainly concern transaminases (ALT, AST) , considered early markers ofliver stress . In almost all the cases described, these changes were reversible upon discontinuation or reduction of the cannabidiol dose However, a few cases of

mild acute hepatitis

have been noted, occurring primarily during co-administration with other molecules having a similar metabolism . Adverse Effect Reported Frequency Severity Elevated Transaminases3-9% (high doses) Almost always mild Nausea/Vomiting

5-10% Mild to moderate Acute Hepatitis (rare) <1% May require discontinuation of treatment How to monitor the liver’s impact of CBD over time? Professionals generally recommend regular monitoring of liver function parameters, especially during the first few weeks following the introduction of CBD. This measure reassures both the patient and the prescriber, thus preventing any undetected adverse effects.For individuals already treated with another medication eliminated via the liver, this precaution becomes essential. This involves standard laboratory monitoring, including the measurement of transaminases and bilirubin, repeated according to the patient’s specific clinical situation. Why are some people more exposed to the risks? Individual vulnerability stems primarily from the overall health context and exposure to other medications metabolized by the same cytochrome enzymes.

• Those with pre-existing liver disease or the elderly should be even more vigilant, as theirliver
• is often less efficient. Genetic differences can amplify or inhibit the
• metabolism of CBD , altering the benefit-risk balance. Hence the importance, in cases of chronic use or self-medication, of consulting a healthcare professional before introducing cannabidiol into one’s routine.Drug interactions: what signals in pharmacovigilance?

Cannabinoids , particularly CBD , present potential risks of drug interactions via the inhibition or induction of certain cytochrome enzymes in the liver. In practice, this means that if a patient is simultaneously taking a medication metabolized by these same enzymes, their concentration can increase or decrease unpredictably. National and international pharmacovigilance databases are gradually accumulating reports of unexpected alterations in the efficacy or tolerability of treatments combined with cannabidiol.Anticonvulsants, anticoagulants, and immunosuppressants are among the most affected therapeutic classes.The effect of CBD on liver metabolism varies depending on the dose.The risks increase with polypharmacy or underlying liver disease. Not all cannabinoids have the same impact on liver cytochromes.

What concrete examples of interactions exist? In epileptic patients treated with valproate or clobazam, the addition of CBD frequently leads to an increase in adverse effects.linked to these molecules, sometimes even requiring a dosage adjustment. Similar cases involve anticoagulant treatments, where increased monitoring of blood tests is systematically recommended. Beyond potential liver disorders, there are also recent investigations into the anti-inflammatory effects of CBD and its involvement in various medical fields.In the field of cancer, certain anticancer molecules are also affected by these pharmacokinetic changes induced by cannabidiol. Although no serious adverse events have been documented on a large scale, caution is still advised, especially since clinical trials initiated on this subject are often short-term.How can the risk of drug interactions with CBD be limited? The doctor-patient dialogue remains the essential cornerstone. Clearly informing patients about all substances consumed, monitoring the clinical response, and adjusting the prescription based on the collected biological results: these practices help prevent most adverse events. When it comes to self-medication, choosing acertified preparationand favoringlow doses limits exposure. Regularliver function tests

or generating

unforeseen drug interactions .Innovation focuses on personalization: adapting the molecule, the dosage form, and the dose to each user. New clinical trials

in advanced stages are specifically examining the liver safety of CBDin “vulnerable” populations. Frequently Asked Questions about CBD and the Liver Can CBD damage the liver with daily use? Current data suggest thatmoderate CBD consumption

is well tolerated by the

liver for most healthy users. The rareadverse effects observed during clinical trials mainly concern high doses

, exceeding those used in everyday life. Controlling thequality of the product and adjusting the dose significantly reduces the risk of liver-related side effects.

Medical monitoring is necessary if amaintenance treatment is being used or in cases of diagnosed liver disease.What are the known drug interactions between CBD and the liver? CBDinterferes with many

medications metabolized by cytochrome P450 enzymes. This primarily concerns certain antiepileptics, anticoagulants, immunosuppressants, andantidepressants. These are all examples where pharmacovigilance experience recommends adjusting dosages. Reporting any

• self-medication to your doctor helps anticipate potential adverse effects. Regular
• liver function tests prevent any abnormal increases in transaminases. MedicationType of interaction observed
• Clobazam Increased plasma levels, increased sedative potential Warfarin Potentialization of anticoagulationShould liver function be monitored while taking CBD even without other medication?

Even without a specific condition or treatment, minimal vigilance is recommended to monitor the liver.

Tolerance when first using CBD . A fewblood tests are enough to dispel any doubts or concerns. This is especially true for prolonged use, increasing doses, or in at-risk individuals. Start with small amounts and increase gradually. Listen to your body’s reactions to CBD .Discuss any new or persistent symptoms with a

healthcare professional .Does CBD offer benefits for the liver in certain conditions? Currently, no large-scale human study has definitively demonstrated a direct benefit of CBD for liver health in chronic liver diseases such as non-alcoholic fatty liver disease, viral hepatitis, or cirrhosis. However, some preclinical results in animal models suggest interesting anti-inflammatory and antifibrotic effects. Indeed, CBD appears in several studies to mitigate the progression of liver damage induced by various toxic or infectious agents, due to its antioxidant and endocannabinoid system-modulating properties. However, the transition to human applications still requires robust evidence from controlled clinical trials to rule out any risk of long-term toxicity or interaction with standard treatments. Therefore, further scientific rigor is necessary before recommending cannabidiol as a “liver protector.” Any therapeutic use should be based on informed medical advice, particularly for individuals with chronic liver disease.

Julien( Rédacteur en chef spécialisé en CBD )