Meta Information
ID:cbd
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/cyp3a4-substrates
Target name:
CYP3A4 Substrates
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD is a potent inhibitor of the CYP3A4 enzyme, which can significantly increase the concentration and risk of side effects from many common medications, including certain statins, calcium channel blockers, and immunosuppressants.
Actionable advice:
CBD inhibits CYP3A4 and can raise levels of CYP3A4 drugs (e.g., some statins, tacrolimus, clobazam). Have your prescriber review and adjust those doses, and watch for increased side effects.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
However, strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir)
may increase the plasma concentrations of amlodipine to a greater extent.
Label source:
Action type:
adjust_with_prescriber
Target id:
/class/cyp2c19-substrates
Target name:
CYP2C19 Substrates
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD strongly inhibits the CYP2C19 enzyme, increasing levels of drugs like the anticonvulsant clobazam, proton pump inhibitors (omeprazole), and some antidepressants (citalopram), which can lead to toxicity.
Actionable advice:
This should be avoided or used with extreme caution and medical supervision alongside medications metabolized by CYP2C19.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
For current labeling information, please visit https://www.fda.gov/drugsatfda
12.5 Pharmacogenomics CYP2C19, a polymorphic enzyme, is involved in the metabolism of omeprazole.
Label source:
Action type:
avoid
Target id:
/intervention/warfarin
Target name:
Warfarin
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD inhibits the CYP2C9 enzyme responsible for metabolizing warfarin, which can dangerously increase warfarin levels and elevate the risk of severe bleeding.
Actionable advice:
Concurrent use should be avoided; if necessary, frequent INR monitoring and dose adjustments under strict medical supervision are required.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CYP2C9, a polymorphic enzyme, is likely to be the principal form of human liver CYP450 that modulates the in vivo anticoagulant activity of warfarin.
Label source:
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Hepatic Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD is metabolized by the liver, and impaired liver function can lead to higher CBD concentrations and an increased risk of side effects, including further liver injury (elevated transaminases).
Actionable advice:
Use should be avoided, or a specialist consulted for significant dose reduction, in cases of moderate to severe liver disease.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
However, there were clinically relevant increases in subjects with moderate (GMR, 2.45; 90%CI, 1.50-4.01) and severe (GMR, 5.15; 90%CI, 2.94-9.00) hepatic impairment, relative to subjects with normal hepatic function.
Label source:
PubMed: Journal of clinical pharmacology (2019)
Source url:
Exact phrase from label:
Adverse effects related to exposure of humans to CBD include changes in appetite, gastrointestinal discomfort, fatigue, and elevated liver aminotransferase enzymes.
Label source:
PubMed: Journal of environmental science and health. Part C, Toxicology and carcinogenesis (2024)
Source url:
Exact phrase from label:
CBD is hydroxylated to 7-OH-CBD and 7-COOH-CBD by cytochrome P450 enzymes CYP3A4 and CYP2C9 in the liver and is excreted mainly in feces and less in urine.
Label source:
PubMed: The Permanente journal (2020)
Action type:
avoid
Target id:
/intervention/valproate
Target name:
Valproate / Valproic Acid
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Concurrent use of CBD and valproate, an anti-seizure medication, is associated with a significantly higher incidence of liver enzyme elevation than with either drug alone.
Actionable advice:
This combination should be avoided, or undertaken only with very close liver function monitoring under specialist care.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Sedation was more frequent with higher N-desmethylclobazam levels in adults (p = 0.02), and AST/ALT levels were significantly higher in participants taking concomitant valproate (p < 0.01).
Label source:
PubMed: Interactions between cannabidiol and commonly used antiepileptic drugs. (PMID 28782097)
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The effects of CBD on fetal development are unknown, and it may cross the placental barrier. The FDA strongly advises against its use during pregnancy due to potential risks.
Actionable advice:
This should be strictly avoided during pregnancy.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Source url:
Exact phrase from label:
For one thing, we need a lot more research into the effects of CBD on pregnant mothers and unborn babies.
Label source:
Anecdotal: WebMD
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD is transferred into breast milk, and its effects on a nursing infant are unknown and potentially harmful. The FDA strongly advises against its use while breastfeeding.
Actionable advice:
It should be avoided completely while breastfeeding.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
Additionally, the CDC states that mothers should be advised not to use products containing CBD in any form while breastfeeding.
Label source:
Anecdotal: Healthline
Action type:
avoid
Target id:
/class/immunosuppressants
Target name:
Calcineurin Inhibitors (e.g., Tacrolimus, Cyclosporine)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD's inhibition of CYP3A4 can lead to dangerously high levels of immunosuppressants like tacrolimus, increasing the risk of kidney damage and other severe toxicities.
Actionable advice:
This combination should be avoided unless managed by a specialist with frequent therapeutic drug monitoring.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Drug interactions are major causes of interindividual variability in tacrolimus exposure and effect. Tacrolimus, a widely used drug in transplant patients, is metabolized by CYP3A4 and CYP3A5. Cannabidiol (CBD) use after transplant is common.
Label source:
PubMed/primary literature: https://pubmed.ncbi.nlm.nih.gov/39921332/
Action type:
avoid
Target id:
/dietary/high-fat-meal
Target name:
High-Fat Meal
Severity:
moderate
Interaction type:
adverse
Nature:
conditional
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
A high-fat meal can increase the absorption and total blood concentration of CBD by roughly four- to five-fold compared with an empty stomach. This large, unpredictable swing in exposure can intensify sedation and amplify CBD's inhibition of drug-metabolizing enzymes (raising levels of co-administered medications); unexpectedly high exposure is a safety concern rather than a simple benefit.
Actionable advice:
It is worth being aware that taking CBD with a high-fat meal can raise its blood levels four- to five-fold, intensifying its effects and its interactions with other drugs. Keeping intake consistent relative to meals and titrating cautiously is a good idea, rather than relying on food to boost the dose.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
SIGNIFICANCE: CBD and metabolite exposures were most affected by a high-fat/calorie meal.
Label source:
PubMed: A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. (PMID 32012251)
Action type:
monitor
Target id:
/class/cns-depressants
Target name:
Central Nervous System Depressants (e.g., Alcohol, Benzodiazepines, Opioids)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD can cause drowsiness and sedation. These effects are additive with other CNS depressants, potentially leading to excessive sleepiness, dizziness, and impaired coordination.
Actionable advice:
Alcohol is best avoided, and caution is warranted alongside other sedating medications, especially when driving.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
clinicians should discuss harm reduction strategies, including avoiding concurrent use with alcohol or other central nervous system depressants such as benzodiazepines, using the lowest effective dose, and avoiding use when driving or operating machinery.
Label source:
PubMed: JAMA (2026)
Source url:
Exact phrase from label:
Cannabis produces sedation, impairs psychomotor performance, and increases blood pressure and heart rate. Pharmacodynamic interactions with other sedatives can potentiate the central effects but can be decreased by psychostimulants.
Label source:
PubMed: CNS & neurological disorders drug targets (2017)
Source url:
Exact phrase from label:
Its consumption can thus have psychoactive effects, such as sedation and drowsiness for example.
Label source:
PubMed: Therapie (2022)
Action type:
avoid
Target id:
/class/cyp2d6-substrates
Target name:
CYP2D6 Substrates
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD is a moderate inhibitor of the CYP2D6 enzyme, which can increase levels of many antidepressants (e.g., SSRIs, tricyclics), antipsychotics, and beta-blockers.
Actionable advice:
This is best used with caution, keeping in mind the potential for increased side effects from medications metabolized by CYP2D6.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Bupropion and its metabolites (hydroxybupropion, erythrohydroxybupropion, threohydroxybupropion) are inhibitors of
CYP2D6.
Label source:
Action type:
informational_none
Target id:
/class/cyp2c9-substrates
Target name:
Drugs Metabolized by CYP2C9
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD inhibits the CYP2C9 enzyme, which can increase levels of certain medications like some NSAIDs (ibuprofen, celecoxib) and antidiabetic drugs (glipizide), potentially increasing their side effects.
Actionable advice:
This is best used with caution when combined with medications metabolized by CYP2C9, and is best avoided completely with warfarin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CYP2C9, a polymorphic enzyme, is likely to be the principal form of human liver CYP450 that modulates the in vivo anticoagulant activity of warfarin.
Label source:
Action type:
avoid
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Beyond the major interaction with warfarin via CYP2C9 inhibition, CBD may have additive blood-thinning effects with other anticoagulants and antiplatelets, theoretically increasing the overall risk of bleeding.
Actionable advice:
This is best used with caution, and it is important to talk to a healthcare provider before combining it with any blood-thinning medications or supplements.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
7.2 CYP450 Interactions CYP450 isozymes involved in the metabolism of warfarin include CYP2C9, 2C19, 2C8, 2C18, 1A2, and 3A4.
Label source:
Action type:
informational_none
Target id:
/class/broad-spectrum-inducers
Target name:
Strong Enzyme Inducers (e.g., Rifampin, St. John's Wort)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Drugs that strongly induce CYP3A4 and CYP2C19 enzymes can significantly accelerate the breakdown of CBD, reducing its blood concentration and effectiveness.
Actionable advice:
This combination is best avoided, or a higher CBD dose anticipated under medical guidance.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
A single dose of four sprays of THC/CBD spray (10.8/10 mg) following repeated doses of rifampicin (600 mg) reduced the Cmax and AUC of all analytes. Cmax reduced from 2.94 to 1.88 ng/mL (-36%), 1.03 to 0.50 ng/mL (-52%) and 3.38 to 0.45 ng/mL (-87%) for THC, CBD and 11-OH-THC, respectively compared to single dose administration of THC/CBD spray alone.
Label source:
PubMed: SpringerPlus (2013)
Source url:
Exact phrase from label:
Conversely, conventional drugs with strong inhibitory or inductive effects on CYP3A4 are expected to affect CBD disposition.
Label source:
PubMed: Journal of clinical psychopharmacology (2019)
Source url:
Exact phrase from label:
The simulated DDI studies using the in vitro-derived values produced AUC0-∞ treatment ratios comparable to observed: itraconazole 1.24 versus 1.07, fluconazole 1.45 versus 1.22, and rifampicin 0.49 versus 0.69.
Label source:
PubMed: CPT: pharmacometrics & systems pharmacology (2023)
Action type:
avoid
Target id:
/dietary/grapefruit-pomelo
Target name:
Grapefruit or Grapefruit Juice
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both CBD and grapefruit are inhibitors of the CYP3A4 enzyme. Consuming them together can amplify this effect, increasing the risk and severity of interactions with other medications metabolized by this pathway.
Actionable advice:
Grapefruit products are best avoided when taking CBD, especially if other medications are being taken.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Among the three major cannabinoids, CBD most potently inhibited CYP3A4 and CYP3A5 (IC(50)=11.7 and 1.65 μM, respectively).
Label source:
PubMed: Life sciences (2011)
Source url:
Exact phrase from label:
Given CBD effects on common biological targets implicated in drug metabolism (e.g., CYP3A4/2C19) and excretion (e.g., P-glycoprotein), the potential for DDIs with commonly used medication is high.
Label source:
PubMed: Journal of clinical medicine (2019)
Source url:
Exact phrase from label:
Cannabidiol (CBD) is known to affect the pharmacokinetics of other drugs through metabolic inhibition of CYP2C19 and CYP3A4. However, there is a lack of in vivo evidence for such drug interactions.
Label source:
PubMed: Cannabis and cannabinoid research (2020)
Action type:
avoid
Target id:
/biomarker/alanine-aminotransferase
Target name:
Liver Enzymes (ALT/AST)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High doses of CBD can cause a dose-dependent elevation in liver enzymes (transaminases), indicating potential liver stress. This risk is higher when combined with other drugs affecting the liver.
Actionable advice:
Regularly monitor liver function tests when taking high doses of CBD or using it with other potentially hepatotoxic medications.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
EPIDIOLEX can cause dose-related elevations of liver transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]). In controlled studies for LGS and DS (10 and 20 mg/kg/day dosages) and TSC (25 mg/kg/day), the incidence of ALT elevations above 3 times the upper limit of normal (ULN) was 13% (10 and 20 mg/kg/day dosages) and 12% (25 mg/kg/day dosage) in EPIDIOLEX-treated patients compared with 1% in patients on placebo.
Label source:
FDA label: Cannabidiol (Epidiolex)
Action type:
monitor
Target id:
/class/antihypertensives
Target name:
Antihypertensive Medications
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD may cause a modest decrease in blood pressure, which could have an additive effect with blood pressure-lowering medications, potentially causing dizziness or lightheadedness.
Actionable advice:
It is a good idea to check blood pressure when starting or adjusting CBD dosage while taking antihypertensive drugs.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In conclusion, chronic administration of CBD reduces ambulatory BP in those with untreated and treated hypertension.
Label source:
PubMed: 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. (PMID 37093160)
Action type:
monitor
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Some evidence suggests CBD may influence glucose metabolism and insulin sensitivity. This could theoretically alter the effects of antidiabetic medications, requiring dose adjustments.
Actionable advice:
Blood glucose levels are best monitored closely when initiating or changing a CBD dose during treatment for diabetes.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Label source:
Action type:
monitor
Target id:
/intervention/caffeine
Target name:
Caffeine
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
CBD may weakly inhibit the CYP1A2 enzyme that metabolizes caffeine, potentially slowing its clearance and prolonging its effects, which could lead to jitteriness or insomnia in sensitive individuals.
Actionable advice:
Consider reducing caffeine intake if you experience increased side effects after starting CBD.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
When caffeine was administered with steady-state CBD, caffeine exposure increased by 15% for Cmax and 95% for AUC0-∞ , tmax increased from 1.5 to 3.0 hours, and t1/2 increased from 5.4 to 10.9 hours compared with caffeine administered with placebo.
Label source:
PubMed: Clinical pharmacology in drug development (2021)
Source url:
Exact phrase from label:
The CBD + Δ9-THC brownie inhibited CYP2C19 > CYP2C9 > CYP3A > CYP1A2 (but not CYP2D6) activity, as evidenced by an increase in the geometric mean ratio of probe drug area under the plasma concentration-time curve (AUC) relative to placebo (AUCGMR ) of omeprazole, losartan, midazolam, and caffeine by 207%, 77%, 56%, and 39%, respectively.
Label source:
PubMed: Clinical pharmacology and therapeutics (2023)
Source url:
Exact phrase from label:
CBD also demonstrated mechanism-based inhibition (KI = 25.63 μM, Kinact = 0.063 min-1) against human CYP1A2-mediated MT metabolism.
Label source:
PubMed: Pharmaceuticals (Basel, Switzerland) (2025)
Action type:
separate
Target id:
/intervention/theophylline
Target name:
Theophylline
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High doses of CBD may weakly inhibit CYP1A2, the enzyme that metabolizes theophylline. This could potentially increase levels of theophylline, a drug with a narrow therapeutic window.
Actionable advice:
This is best used with caution, and it is worth monitoring for theophylline side effects when using high-dose CBD.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
If theophylline is being initiated in a patient who is already taking a drug that inhibits theophylline clearance (e.g., cimetidine, erythromycin), the dose of theophylline required to achieve a therapeutic serum theophylline concentration will be smaller.
Label source:
Action type:
monitor
Target id:
/condition/seizure-disorder
Target name:
Seizure Disorder / Epilepsy
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While used to treat certain seizures, CBD can also alter the blood concentrations of other anti-seizure medications through metabolic enzyme inhibition, requiring careful dose management by a neurologist.
Actionable advice:
For epilepsy, this is generally best used only under the direct supervision of a physician who can manage drug interactions.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Because of potential inhibition of enzyme activity, consider a reduction in dosage of substrates of UGT1A9, UGT2B7, CYP2C8, and CYP2C9, as clinically appropriate, if adverse reactions are experienced when administered
Label source:
FDA label: Cannabidiol (Epidiolex)
Action type:
informational_none