CBD and losartan share a metabolic pathway in the liver, and combining them raises the risk of a drug interaction that could amplify losartan’s blood-pressure-lowering effect or its side effects. The interaction centers on an enzyme called CYP2C9, which the liver uses to convert losartan into its active form. CBD inhibits that same enzyme, slowing down how your body processes losartan. Whether this matters for you depends on the dose of CBD, the form you take it in, and how your individual liver handles both substances.
How the Interaction Works
Losartan is a blood-pressure medication classified as an angiotensin II receptor blocker, or ARB. When you swallow a losartan tablet, your liver converts it into a more potent metabolite called E-3174, and this metabolite does most of the actual work of lowering blood pressure.1PubMed. Role of CYP2C9 polymorphism in losartan oxidation The enzyme responsible for that conversion is CYP2C9, one of several liver enzymes in the cytochrome P450 family.
CBD is a potent inhibitor of CYP2C9. In laboratory studies, nearly all major cannabinoids blocked CYP2C9 activity at very low concentrations.2PubMed. Cannabinoid Interactions with Cytochrome P450 Drug Metabolism: a Full-Spectrum Characterization A systematic review of the literature confirmed that CBD consistently acts as a potent inhibitor of several CYP enzymes, including CYP2C9 and the closely related CYP2C19.3PubMed Central. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants When CBD occupies those enzymes, losartan has to wait its turn, so to speak. The result is that losartan and its metabolites linger in your bloodstream longer and at higher concentrations than your doctor intended when they chose your dose.
A published review of potential CBD drug interactions explicitly flags CYP2C8/9 substrates like losartan as having an increased risk of side effects when co-administered with CBD, and recommends either avoiding the combination, reducing the substrate dose, or closely monitoring for adverse effects.4PubMed Central. Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use Losartan also undergoes metabolism through a second pathway, UGT2B7, which CBD may also inhibit, adding another layer to the interaction.4PubMed Central. Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use
What a Clinical Trial Actually Measured
Most drug-interaction research on CBD comes from lab dishes and computer models, but there is at least one human trial that directly measured what happens to losartan levels when people take CBD. In a study of healthy adults, participants consumed a brownie containing both CBD and THC. Compared to a placebo brownie, the cannabinoid-laced version increased the amount of losartan circulating in the blood by about 77%, measured as the area under the plasma concentration-time curve.3PubMed Central. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants That is a substantial jump. For context, the same study showed even larger effects on omeprazole (a stomach acid drug metabolized by CYP2C19), whose levels rose by about 207%.
A 77% increase in losartan exposure does not automatically mean you will feel terrible or have dangerously low blood pressure, but it is the kind of change that could matter clinically. It effectively means your prescribed dose of losartan is acting more like a higher dose. Symptoms of excessive losartan exposure can include dizziness, lightheadedness when standing, and in extreme cases, fainting, especially in people who are already on the lower end of normal blood pressure or who take other medications that lower it further.
Does Dose Matter?
Enormously. The CBD market includes products ranging from a few milligrams per serving (typical of wellness gummies and tinctures) to hundreds of milligrams per dose (used in clinical epilepsy treatment, where the FDA-approved product Epidiolex can reach 10-20 mg per kilogram of body weight daily). The interaction risk scales with how much CBD actually reaches your liver.
One analysis concluded that clinically relevant drug interactions with CBD probably arise only at doses above roughly 300 mg per day.5PubMed Central. Drug Interactions of Tetrahydrocannabinol and Cannabidiol in Cannabinoid Drugs That is well above what most people take from an over-the-counter supplement. If you are using a 25 mg CBD gummy once a day, the enzyme inhibition is likely far smaller than what was measured in the clinical trial above, which used a more substantial dose. But “likely smaller” is not the same as “zero,” and this threshold has not been rigorously tested across different patient populations or with the wide variety of products available.
Oral bioavailability is another wild card. When you swallow CBD, an estimated 70 to 75% of the absorbed dose gets removed by the liver before it even reaches your general circulation.6PubMed. Critical Aspects Affecting Cannabidiol Oral Bioavailability and Metabolic Elimination, and Related Clinical Implications That means most of the CBD you take by mouth is already interacting heavily with liver enzymes on its first pass through. Paradoxically, this is both reassuring (less CBD reaches the rest of your body) and concerning (the liver is exactly where the interaction with losartan metabolism takes place). Taking CBD with a fatty meal, or using sublingual or inhaled products, can change how much CBD the liver sees and when.
CBD’s Own Effect on Blood Pressure
The metabolic enzyme story is only half the picture. CBD, independently of any drug interaction, appears to lower blood pressure on its own. In a crossover study of healthy volunteers, a single dose of CBD reduced resting systolic blood pressure by about 6 mmHg and blunted the blood-pressure spike that normally accompanies physical or cold stress.7PubMed Central. A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study A later trial in patients with actual hypertension found that CBD taken daily for a few weeks reduced 24-hour average systolic blood pressure by roughly 5 mmHg and diastolic pressure by about 2 mmHg, with no serious side effects reported.8PubMed Central. Chronic Effects of Oral Cannabidiol Delivery on 24-h Ambulatory Blood Pressure in Patients with Hypertension (HYPER-H21-4): A Randomized, Placebo-Controlled, and Crossover Study
Those drops are modest, but if CBD is simultaneously making losartan act like a higher dose and independently pushing blood pressure down, the combined effect could be enough to cause symptoms, especially when you stand up quickly, exercise, get dehydrated, or are exposed to heat. The risk is not catastrophic for most people, but it is additive in a way that neither your losartan prescriber nor the CBD product label is accounting for.
Research into CBD’s cardiovascular mechanisms suggests it causes relaxation of blood vessel walls and may alter how the autonomic nervous system regulates heart rate and vascular tone.9PubMed Central. Is the cardiovascular system a therapeutic target for cannabidiol? Some studies have also found that CBD shifts the balance of the autonomic nervous system toward parasympathetic (rest-and-digest) dominance, as reflected in heart rate variability measurements.10The FASEB Journal. The Effects of Acute Cannabidiol on Autonomic Balance Other work has found that acute CBD ingestion decreased heart rate.11PubMed Central. Comparison of Five Oral Cannabidiol Preparations in Adult Humans: Pharmacokinetics, Body Composition, and Heart Rate Variability These are generally benign changes in a healthy person, but they matter when stacked on top of a medication whose entire purpose is to lower cardiovascular strain.
Why Your Doctor Probably Does Not Know You Take CBD
One of the most practically important findings in this area is not pharmacological at all. A survey of emergency department patients found that about 29% reported using CBD at home. Among those CBD users, two-thirds were also taking at least one prescription medication with a potential drug interaction. The most common co-used categories were anxiety medications, followed by antihypertensives (which includes drugs like losartan), reported by about 44% of the at-risk group.12Annals of Emergency Medicine. Emergency Department Patient Use of Cannabidiol (CBD) and Potential Drug-Interactions
Meanwhile, primary care providers frequently report that their patients do not mention CBD use, and many providers feel uncertain about how to counsel patients on it.13PEC Innovation. Primary care provider attitudes, experiences and practices about cannabidiol (CBD) and barriers to patient-provider communication about CBD use: A qualitative study The practical consequence is that many people taking losartan and CBD simultaneously are doing so in a blind spot. Their doctor does not know, their pharmacist was never told, and the CBD product itself almost certainly does not carry a warning about CYP2C9 interactions. If you are in this group, simply mentioning your CBD use at your next visit lets your doctor watch for signs that losartan is hitting harder than expected and adjust accordingly.
What You Might Actually Feel
If the interaction is clinically significant for you, the most common signals are related to blood pressure dropping lower than intended. Dizziness when standing up from a chair or getting out of bed, feeling lightheaded during exercise, and unusual fatigue are the main ones. Some people notice headaches or a general “woozy” feeling. In more pronounced cases, you could faint, which is especially dangerous for older adults at risk of falls.
Losartan is also used to protect the kidneys in people with diabetes, and its potassium-sparing properties mean that higher-than-intended losartan levels could contribute to elevated blood potassium. This is unlikely from a mild interaction but worth mentioning because high potassium can cause heart rhythm problems and is something doctors already monitor in people on ARBs. If you are on losartan for kidney protection and also using CBD, periodic blood work becomes more rather than less important.
The Product Quality Problem
Even if you carefully select a low dose of CBD to minimize interaction risk, the supplement you buy may not contain what it says on the label. In a large analysis of commercially available CBD products, only about 42% fell within 10% of the CBD content claimed on the label. Roughly 40% contained less than 90% of the advertised amount, and 18% contained more than 110%.14Science of The Total Environment. Heavy metal and phthalate contamination and labeling integrity in a large sample of US commercially available cannabidiol (CBD) products That means the “25 mg” gummy you are relying on to keep you in a safe dose range might actually deliver 10 mg or 40 mg.
Contamination is also a concern. Testing of over 200 CBD products found heavy metals detected in about a fifth of them (lead being the most common), residual solvents in the vast majority, and pesticides in about 15%.15Frontiers in Pharmacology. Product labeling accuracy and contamination analysis of commercially available cannabidiol product samples Lead in particular was detected in 42% of edible CBD products in a separate study, with some exceeding California’s daily lead consumption threshold.14Science of The Total Environment. Heavy metal and phthalate contamination and labeling integrity in a large sample of US commercially available cannabidiol (CBD) products These contaminants are not directly related to the losartan interaction, but they add a layer of unpredictability to what you are actually putting in your body when you use an unregulated supplement alongside a prescription drug.
If you do choose to use CBD alongside losartan, choosing products that provide third-party certificates of analysis (COAs) from independent labs at least helps verify the CBD content, even if it does not eliminate the interaction risk.
Cross-Talk Between the Endocannabinoid and Blood Pressure Systems
Beyond the straightforward liver-enzyme conflict, there is emerging evidence that the body’s own cannabinoid signaling system and the system that losartan targets (the renin-angiotensin system, or RAS) are biologically intertwined. When angiotensin II activates its receptor (the same receptor losartan blocks), it triggers the release of the body’s own endocannabinoids, particularly one called 2-AG. Those endocannabinoids then feed back to modify the effects of angiotensin II.16PubMed Central. Cross-Talk between the (Endo)Cannabinoid and Renin-Angiotensin Systems: Basic Evidence and Potential Therapeutic Significance This cross-modulation has been observed in cell cultures, isolated blood vessels, and animal models.17PubMed Central. The interaction between the endocannabinoid system and the renin angiotensin system and its potential implication for COVID-19 infection
Animal research has found that endocannabinoid levels in brain regions involved in blood pressure regulation vary depending on the activity of the renin-angiotensin system, suggesting these two systems are in constant dialogue.18Frontiers in Physiology. Medullary Endocannabinoids Contribute to the Differential Resting Baroreflex Sensitivity in Rats with Altered Brain Renin-Angiotensin System Expression What this means for someone taking exogenous CBD alongside losartan is still speculative, but the implication is that adding CBD to a system already being manipulated by an ARB may produce effects beyond what simple enzyme inhibition would predict. Researchers have even explored whether the CBD-losartan combination could be therapeutically useful: one lab study found that co-treating cells with low concentrations of both losartan and CBD produced a synergistic 80% reduction in nitric oxide release from immune cells in the brain, far more than either compound managed alone.19PubMed Central. An Emerging Strategy for Neuroinflammation Treatment: Combined Cannabidiol and Angiotensin Receptor Blockers Treatments Effectively Inhibit Glial Nitric Oxide Release That is a cell-culture result with no direct clinical application yet, but it hints that the interaction is more complex than a simple enzyme-blocking story.
Practical Steps if You Use Both
None of this means you must never take CBD if you are on losartan. It means the combination deserves active management rather than casual use. A few concrete things are worth doing:
- Tell your prescriber: Even if it feels awkward, disclosing CBD use lets your doctor factor it into dosing decisions and monitoring schedules.
- Monitor your blood pressure at home: A simple wrist or arm cuff, used consistently at the same time of day, can reveal whether your readings are trending lower than usual after starting CBD.
- Start CBD low and go slow: If you are beginning CBD while already on losartan, use the lowest effective dose and increase gradually over weeks, watching for dizziness or lightheadedness.
- Time your doses apart: While this will not eliminate the enzyme interaction (CBD’s inhibitory effect on CYP2C9 can last for hours), spacing the two doses by several hours may reduce peak overlap in the liver.
- Watch for potassium: If your doctor already checks your kidney function and electrolytes, make sure those tests continue. Mention the CBD so they can interpret the results in context.
For people using very low doses of CBD (under 25 mg per day), the practical risk of a dangerous interaction with losartan is likely small, though not zero. For people using CBD at therapeutic doses for epilepsy, chronic pain, or anxiety (100 mg and above), the interaction is real enough that dose adjustments to losartan or additional monitoring become sensible precautions. The 300 mg threshold mentioned in the literature is a rough guideline, not a bright line, and individual variation in liver enzyme activity means some people will be more sensitive than others.
Genetic Variation in CYP2C9
Not everyone metabolizes losartan at the same rate to begin with. Genetic variants of CYP2C9 are well documented, and people carrying certain versions of the gene already process losartan more slowly. If you are a naturally slow metabolizer and then add CBD on top, the cumulative enzyme inhibition could be considerably larger than what the average-population studies suggest. Pharmacogenomic testing can identify these variants, and some health systems now test for CYP2C9 status before prescribing certain drugs. If you already know you are a CYP2C9 poor metabolizer, that is extra reason to be cautious about adding CBD.
The flip side is also true: people who are ultra-rapid metabolizers of CYP2C9 may experience less of an interaction because they start with more enzyme capacity to spare. Without genetic testing, though, you are guessing, and the conservative approach is to assume average metabolism and manage accordingly.