Table 3

Summary of cannabinoid-drug interactions used with permission from Samer Narouze, MD, PhD 63–67

EnzymeDrugsEffects and interventions
CYP2C9
CYP2C9 inducers

  • Antiarrhythmics: amiodarone

  • Anticonvulsants: valproic acid

  • Antidepressants: fluoxetine

  • Fluconazole, metronidazole, sulfamethoxazole

  • Decrease THC level

  • Unlikely to have significant effect on CBD

CYP2C9 inhibitors

  • Carbamazepine, rifampin

  • Increase THC level

  • Unlikely to have significant effect on CBD

CYP2C9 substrates

  • Warfarin

  • Buprenorphine

  • Non-steroidal anti-inflammatory drugs (NSAIDs): celecoxib, naproxen,

  • Anticonvulsants: phenobarbital, phenytoin

  • Fluvastatin, rosiglitazone, rosuvastatin, sulfonylureas, losartan, valsartan

  • CBD and possibly THC may increase drug levels

Interventions:

  • Decrease dose of substrate

  • Monitor for toxicity and side effects

  • Check INR within 3 days

CYP2C19
CYP2C19 inducers

  • Anticonvulsants: carbamazepine, phenytoin, phenobarbital

  • Rifampin, rifampicin, ketoconazole, St. John’s wort

  • Decrease CBD and THC levels

CYP2C19 inhibitors

  • Antidepressants: fluoxetine, fluvoxamine

  • Chloramphenicol, felbamate, isoniazid

  • Protease inhibitors

  • Increase CBD and THC levels

CYP2C19 substrates

  • Antidepressants: amitriptyline, citalopram, bupropion

  • Anticonvulsants: clobazam, diazepam, phenytoin, phenobarbital

  • Antiplatelets: clopidogrel

  • Proton pump Inhibitors: omeprazole, pantoprazole

  • CBD and THC may increase drug levels

Interventions:

  • Decrease dose of substrate

  • Monitor for toxicity

  • Consider using alternative antiplatelet instead of clopidogrel

CYP2D6
CYP2D6 Substrates

  • Opioids: codeine, morphine, hydrocodone, tramadol

  • Anticonvulsants: valproate

  • Antidepressants: amitriptyline, citalopram, nortriptyline

  • Antipsychotics: clozapine, haloperidol, risperidone

  • Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone

  • β-blockers: carvedilol, metoprolol

  • CBD>THC may increase drug levels.

Interventions:

  • Decrease dose of substrate

  • Monitor for toxicity and side effects

  • Monitor for opioids augmentation

  • Monitor QTc for antidepressants and antiarrhythmics

CYP3A4
CYP3A4 Inducers

  • Anticonvulsants: carbamazepine, phenytoin, phenobarbital, topiramate

  • Cimetidine, pioglitazone, rifampin, St. John’s wort

  • Decrease CBD and THC levels

CYP3A4 Inhibitors

  • Antiarrhythmic: amiodarone, dronedarone, quinidine, diltiazem, verapamil

  • Anticonvulsants: valproate

  • Antifungals: ketoconazole, itraconazole, posaconazole

  • Macrolides: clarithromycin, erythromycin

  • Protease inhibitors

  • Tyrosine kinase inhibitors

  • Increase CBD and THC levels

CYP3A4 Substrates

  • Opioids: fentanyl, alfentanil, methadone

  • · Benzodiazepines: midazolam

  • Calcium channel blockers: amlodipine, felodipine

  • Calcineurin inhibitor: cyclosporine, tacrolimus

  • PDE5 inhibitors: sildenafil

  • Propafenone

  • Statins

  • Zaleplon, zopiclone, zolpidem

  • Increase CBD and THC levels

UGT1A9 (Phase II)
UGT1A9 Substrates

  • Analgesics/NSAIDs: acetaminophen, ibuprofen, diflunisal

  • Anesthetics: propofol

  • Anticonvulsants: valproate

  • Antipsychotics: haloperidol

  • DOACs: dabigatran

  • Canagliflozin, dapagliflozin, irinotecan, mycophenolate mofetil, regorafenib, sorafenib

  • CBD increases substrate levels

Interventions:

  • Consider decreasing substrate dose

  • Monitor for side effects or toxicity

UGT2B7 (Phase II)
UGT2B7 substrates

  • Opioids: hydromorphone, morphine, buprenorphine

  • NSAIDs: ibuprofen, naproxen.

  • Benzodiazepines: lorazepam

  • Anticonvulsants: carbamazepine, valproate, lamotrigine

  • Statins: lovastatin, simvastatin

  • Ezetimibe, losartan

p-glycoprotein (transport protein)
P-glycoprotein substrates

  • DOACs: dabigatran, apixaban, rivaroxaban

  • Digoxin, loperamide

  • CBD and possibly THC may be a substrate and inhibitor of P-glycoprotein

Intervention:

  • Decrease dose of substrate

  • Monitor for toxicity and side effects

  • CBD, cannabidiol; INR, international normalized ratio ; THC, tetrahydrocannabinol.