Evidence-based cannabis–medication interactions for 40 medications across 15 categories
Coumadin · Jantoven
CBD strongly inhibits CYP2C9, the primary enzyme responsible for warfarin metabolism. This can significantly increase warfarin blood levels and bleeding risk.
Eliquis
CBD inhibits CYP3A4 and P-glycoprotein, both involved in apixaban metabolism and transport. May increase apixaban exposure and bleeding risk.
Xarelto
Similar to apixaban, rivaroxaban is metabolized by CYP3A4 and transported by P-gp. CBD inhibition may increase drug exposure.
Onfi · Sympazan
CBD inhibits CYP2C19, which metabolizes clobazam to its active metabolite N-desmethylclobazam. This interaction is well-documented in Epidiolex clinical trials and can cause significant sedation.
Depakote · Depakene · Stavzor
CBD and valproate both carry hepatotoxicity risk. Concurrent use significantly increases the risk of liver enzyme elevation and liver damage.
Dilantin · Phenytek
CBD inhibits CYP2C9 and CYP2C19, both involved in phenytoin metabolism. May increase phenytoin levels and toxicity risk.
Tegretol · Carbatrol · Epitol
CBD may inhibit CYP3A4-mediated carbamazepine metabolism. Conversely, carbamazepine is a strong CYP3A4 inducer that may reduce CBD levels.
Topamax · Trokendi XR
Additive CNS depressant effects. Both agents can cause cognitive slowing and sedation.
Prozac · Sarafem
CBD inhibits CYP2D6, which metabolizes fluoxetine. May increase fluoxetine levels. Both agents also affect serotonin signaling.
Zoloft
CBD may mildly inhibit CYP2D6-mediated sertraline metabolism. Clinical significance is generally low.
Phenelzine (Nardil) · Tranylcypromine (Parnate) · Selegiline (Emsam)
MAOIs combined with cannabis (particularly THC) may cause hypertensive crisis and serotonin syndrome. Cannabis can trigger sympathomimetic effects that interact dangerously with MAOIs.
Amitriptyline (Elavil) · Nortriptyline (Pamelor) · Imipramine (Tofranil)
CBD inhibits CYP2D6, which metabolizes most TCAs. THC adds CNS depressant and anticholinergic effects. Combined use increases sedation and cardiac risk.
Clozaril · FazaClo
Cannabis smoke inhibits CYP1A2 (via polycyclic aromatic hydrocarbons), which metabolizes clozapine. Smoking cannabis can significantly alter clozapine levels. THC may also worsen psychotic symptoms.
Haldol
CBD inhibits CYP2D6-mediated haloperidol metabolism. THC may worsen psychotic symptoms and counteract antipsychotic effects.
Diazepam (Valium) · Lorazepam (Ativan) · Alprazolam (Xanax) · Clonazepam (Klonopin)
CBD inhibits CYP3A4, which metabolizes most benzodiazepines. THC adds CNS depressant effects. Combined use significantly increases sedation and respiratory depression risk.
Ambien · Edluar · Intermezzo
CBD may inhibit CYP3A4-mediated zolpidem metabolism. Both agents cause CNS depression and sedation.
Oxycodone (OxyContin) · Hydrocodone (Vicodin) · Morphine · Fentanyl · Codeine
Cannabis and opioids have additive CNS depressant effects. However, evidence also suggests cannabis may allow opioid dose reduction (opioid-sparing effect). The interaction is complex and bidirectional.
Dolophine · Methadose
CBD inhibits both CYP3A4 and CYP2D6, the primary enzymes metabolizing methadone. This can significantly increase methadone levels and QT prolongation risk.
Lanoxin
Cannabis may inhibit P-glycoprotein, increasing digoxin absorption. THC also causes tachycardia which can worsen heart failure and interact with digoxin's rate-controlling effects.
Metoprolol (Lopressor) · Atenolol (Tenormin) · Propranolol (Inderal)
THC causes initial tachycardia and blood pressure changes that may partially counteract beta-blocker effects. CBD may inhibit CYP2D6 metabolism of some beta-blockers.
Atorvastatin (Lipitor) · Simvastatin (Zocor) · Lovastatin (Mevacor)
CBD inhibits CYP3A4, which metabolizes atorvastatin, simvastatin, and lovastatin. This can increase statin levels and myopathy risk.
Amlodipine (Norvasc) · Diltiazem (Cardizem) · Verapamil (Calan)
CBD inhibits CYP3A4, which metabolizes most calcium channel blockers. May increase drug levels and hypotensive effects.
Prograf · Astagraf XL
Tacrolimus has a very narrow therapeutic index and is metabolized by CYP3A4 and transported by P-gp. CBD inhibition of both pathways can dramatically increase tacrolimus levels.
Neoral · Sandimmune · Gengraf
Like tacrolimus, cyclosporine has a narrow therapeutic index and is metabolized by CYP3A4/P-gp. CBD can significantly increase cyclosporine exposure.
Camptosar
Irinotecan is metabolized by CYP3A4 to its active metabolite SN-38. CBD inhibition may alter irinotecan pharmacokinetics and increase toxicity.
Taxotere
Docetaxel is a CYP3A4 and P-gp substrate. CBD inhibition may increase docetaxel exposure and toxicity.
Humalog · Lantus · NovoLog · Levemir
Cannabis can affect blood glucose levels. THC may cause hyperglycemia acutely; CBD may have insulin-sensitizing effects. The interaction with insulin is complex.
Glucophage · Glumetza · Fortamet
CBD may have complementary effects on insulin sensitivity and glucose metabolism. Limited direct interaction data.
Ritonavir (Norvir) · Atazanavir (Reyataz) · Lopinavir (Kaletra)
Protease inhibitors (especially ritonavir) are potent CYP3A4 inhibitors themselves and may increase cannabinoid levels. Conversely, CBD may affect PI metabolism.
Sustiva · Atripla
Efavirenz is a CYP3A4 inducer that may reduce cannabinoid levels. Limited direct clinical data.
Ibuprofen (Advil) · Naproxen (Aleve) · Celecoxib (Celebrex)
CBD inhibits CYP2C9, which metabolizes ibuprofen and celecoxib. May increase NSAID levels. Both agents have anti-inflammatory effects that may be additive.
Tylenol · Panadol
Cannabis smoke may inhibit CYP1A2, which metabolizes acetaminophen. Both agents are hepatically processed. High doses of both may increase liver stress.
Adderall · Vyvanse · Ritalin (methylphenidate) · Concerta
THC and stimulants both affect cardiovascular function and dopamine signaling. Combined use increases heart rate and blood pressure and may worsen anxiety.
Coffee · Energy drinks · Caffeine supplements
Cannabis smoke inhibits CYP1A2, which metabolizes caffeine. May increase caffeine levels and effects.
Beer · Wine · Spirits
Alcohol and THC have synergistic CNS depressant effects. Combined use ("crossfading") significantly impairs driving ability and cognitive function beyond either substance alone.
Lithobid · Eskalith
THC may increase lithium levels through unclear mechanisms. Both agents affect mood and neurological function. Cannabis use may destabilize bipolar disorder.
Theo-24 · Theochron · Uniphyl
Theophylline has a narrow therapeutic index and is metabolized by CYP1A2. Cannabis smoke can alter CYP1A2 activity and change theophylline levels.
Rifadin · Rimactane
Rifampin is a potent CYP3A4 inducer that can dramatically reduce CBD and THC plasma levels, potentially reducing therapeutic efficacy.
Prilosec · Nexium (esomeprazole) · Prevacid (lansoprazole)
CBD inhibits CYP2C19, which metabolizes omeprazole and other PPIs. May increase PPI levels.
Viagra · Cialis (tadalafil) · Levitra (vardenafil)
CBD inhibits CYP3A4-mediated PDE5 inhibitor metabolism. THC causes vasodilation. Combined use may cause significant hypotension.
The majority of cannabis–drug interactions occur through the cytochrome P450 (CYP450) enzyme system in the liver. Both CBD and THC inhibit multiple CYP450 enzymes, which can increase or decrease the blood levels of co-administered medications.
Inhibited by: CBD (strong)
Affected drugs: Warfarin, NSAIDs, phenytoin
Inhibited by: CBD (moderate)
Affected drugs: Clobazam, omeprazole, citalopram
Inhibited by: CBD (moderate)
Affected drugs: Benzodiazepines, statins, tacrolimus
Inhibited by: CBD (moderate)
Affected drugs: Antidepressants, opioids, antipsychotics
Inhibited by: Cannabis smoke
Affected drugs: Clozapine, theophylline, caffeine
Inhibited by: CBD
Affected drugs: Digoxin, tacrolimus, apixaban
Sources: Zendulka et al. (2016) Pharmacology; Stout & Cimino (2014) Drug Metabolism Reviews; Bornheim & Grillo (1998) Biochemical Pharmacology
Condition Guides with Drug Interaction Data