Summary: Cannabinoids (especially CBD and, to a lesser extent, THC and some metabolites) can alter the way many prescription drugs are metabolized by inhibiting or inducing cytochrome P450 enzymes and certain transporters (e.g., P-glycoprotein). This can raise or lower drug concentrations, sometimes producing clinically important effects — especially with narrow-therapeutic-index drugs (e.g., warfarin, tacrolimus, certain antiepileptics, and some immunosuppressants). Always consult the prescriber and monitor (labs, symptoms) when starting/stopping cannabis products.

How cannabinoids affect drug metabolism — the CYP basics (concise primer)

• The cytochrome P450 (CYP) enzyme family in the liver (and gut) metabolizes the majority of prescription drugs. Key isoforms relevant to cannabinoids include CYP3A4, CYP2C9, CYP2C19, CYP2D6, CYP2B6, and others.
• CBD is a known inhibitor of multiple CYP isoforms (notably CYP3A4 and CYP2C19 and also CYP2C9, CYP2D6 to varying degrees), meaning CBD can reduce the metabolism of drugs using those enzymes and raise their blood levels. THC and cannabinoid metabolites can also inhibit (and sometimes induce) certain CYPs. The degree of inhibition depends on dose, formulation (isolated CBD vs. full-spectrum cannabis), route (oral vs inhaled), and product purity.
• Some cannabinoids affect drug transporters (e.g., P-glycoprotein), altering absorption and excretion of drugs that are transporter substrates.

Which commonly prescribed drugs may interact — short list with mechanisms and clinical notes

Below are high-priority drugs/classes (selected because they are commonly prescribed, have narrow therapeutic indices, or have documented case reports/studies with cannabinoids). For each: mechanism → what can happen → practical monitoring advice.

1. Warfarin (anticoagulant)

• Mechanism: Warfarin is metabolized primarily by CYP2C9 (and CYP3A4/CYP1A2 to a lesser extent). CBD and some cannabinoids inhibit CYP2C9 and CYP3A4, which can raise warfarin levels and increase INR/bleeding risk.
• Evidence: Multiple case reports and small series show elevated INR after initiation/escalation of CBD or cannabis products; systematic reviews flag warfarin among the most reported interactions.
• Actionable: If a patient on warfarin uses cannabis/CBD: check INR more frequently after starting/changing product; expect possible need to lower warfarin dose; coordinate with anticoagulation service.

2. Tacrolimus / Sirolimus (calcineurin inhibitors, immunosuppressants)

• Mechanism: Both are mainly CYP3A4 substrates with narrow therapeutic windows. Cannabinoids (especially CBD) can inhibit CYP3A4, raising levels and risk of nephrotoxicity, neurotoxicity, or infection.
• Evidence & caution: Case reports and reviews emphasize concern; transplant teams often advise avoiding unregulated cannabinoids or, if used, close therapeutic drug monitoring.

3. Anti-epileptics (e.g., clobazam, valproate, carbamazepine, phenytoin)

• Mechanism: CBD interacts with clobazam via CYP2C19 (increases active metabolite) causing excess sedation; other AEDs may be affected through CYP inhibition/induction. Some AEDs (like carbamazepine, phenytoin) can induce CYPs and may lower cannabinoid levels.
• Clinical note: For patients on AEDs, changes to seizure control or increased adverse effects have been reported — monitor drug levels and clinical response if cannabinoids are started/stopped.

4. Statins (especially simvastatin, atorvastatin)

• Mechanism: Many statins are metabolized by CYP3A4 (simvastatin/atorvastatin); inhibition can raise statin levels → increased myopathy risk. Some statins (pravastatin, rosuvastatin) rely less on CYP3A4 and are lower risk.
• Actionable: Prefer statins with minimal CYP3A4 metabolism if patient is using high-dose CBD or frequent cannabis, or counsel on symptoms (muscle pain) and consider CK monitoring when appropriate.

5. Benzodiazepines & CNS depressants (e.g., diazepam, alprazolam); opioids

• Mechanism: Many benzodiazepines are CYP3A4 substrates; opioids vary (e.g., oxycodone CYP3A4/CYP2D6 pathways). CBD/THC effects can increase sedation when combined and can alter metabolism via CYP inhibition, increasing concentrations.
• Clinical note: Even without large PK changes, additive CNS depression (drowsiness, respiratory depression with opioids) is a real safety concern — caution with co-use, especially in older adults.

6. Antidepressants / Antipsychotics (SSRIs, TCAs, some antipsychotics)

• Mechanism: Many are substrates of CYP2D6 and CYP2C19. CBD and cannabinoids can inhibit these isoforms, potentially raising drug levels and adverse effects (e.g., QT prolongation risk with some agents, increased sedation).
• Actionable: Monitor for increased side effects (sedation, anticholinergic effects, extrapyramidal symptoms) and consider dose adjustments under clinician supervision.

7. Calcium channel blockers, beta blockers, certain antihypertensives

• Mechanism: Several are metabolized by CYP3A4 or CYP2D6. CBD can alter levels and sometimes blunt effects; conversely, cannabinoids can alter hemodynamics (orthostasis) — additive effects matter.
• Practical: Monitor blood pressure and heart rate after starting cannabinoids.

Why timing, dose, and product type matter

• Oral CBD (oil/tinctures, edibles) undergoes first-pass metabolism and is most likely to produce clinically significant CYP inhibition because exposures are higher and longer. Inhaled cannabis (smoking/vaping) produces faster but often lower systemic CBD exposure (though THC exposure is significant) — both routes can interact, but oral forms of CBD carry higher interaction risk for many drugs.
• Product variability: unstandardized over-the-counter products vary in CBD/THC content and contaminants; pharmaceutical-grade CBD (Epidiolex) has documented PK interactions in trials. Unregulated products increase unpredictability.

Practical clinical guidance (patient-facing checklist)

1. Tell every prescriber and pharmacist if you use cannabis products — name the product, dose, route, and frequency. (This includes over-the-counter CBD.)
2. High priority to monitor: If you are on warfarin, tacrolimus/sirolimus, narrow-therapeutic-index antiepileptics, many immunosuppressants, or certain oncology drugs — coordinate close lab monitoring (INR, drug troughs) and dose review.
3. Start low / go slow: If a clinician approves trying cannabinoids, start at a low dose and monitor for side effects or lab abnormalities. Do not abruptly stop or start cannabis products without medical supervision if you're on interacting drugs.
4. Watch for additive effects: sedation, orthostatic hypotension, and impaired cognition — especially with benzodiazepines, opioids, antidepressants, antipsychotics.
5. Prefer trusted products with known composition or pharmaceutical formulations when concomitant drug use is necessary. Unlabeled or variable products make risk impossible to quantify.

Research & evidence quality — what we know and gaps

• There are robust in-vitro and pharmacokinetic studies showing cannabinoids inhibit multiple CYP enzymes; clinical evidence consists largely of case reports, small PK studies, and a few controlled trials (e.g., with pharmaceutical CBD). Systematic reviews flag interactions with warfarin, valproate, tacrolimus, sirolimus, and antiepileptics as most reported — but the overall evidence quality varies, and much is product- and dose-dependent.
• Regulatory guidance (FDA) and transplant/anticoagulation clinicians emphasize caution and therapeutic monitoring. Large, controlled interaction studies with commonly–used prescription drugs are still limited; ongoing trials are assessing specific interaction magnitudes.

Short, clinician-ready summary (one paragraph)

Cannabinoids — especially oral CBD — are inhibitors of several CYP enzymes (CYP3A4, CYP2C9, CYP2C19, CYP2D6 among others) and can therefore increase blood concentrations of drugs metabolized by those pathways. Clinically relevant interactions have been most frequently reported with warfarin, calcineurin inhibitors (tacrolimus/sirolimus), certain antiepileptics, and other narrow-therapeutic-index agents; additive CNS depression with benzodiazepines/opioids is also a safety risk. When patients on these medications use cannabis/CBD, prescribers should consider increased monitoring (INR, drug troughs), dose adjustments, and patient counseling.

References / further reading (select)

• Balachandran P, et al. Cannabidiol Interactions with Medications, Illicit Substances … 2021. (comprehensive review on CBD interactions).
• Kocis PT, et al. Delta-9-Tetrahydrocannabinol and Cannabidiol Drug-Drug Interaction list (2020).
• Systematic review: Nachnani R, et al. (2024) Systematic review of drug–drug interactions of delta-9-THC & CBD. (highlights warfarin, valproate, tacrolimus/sirolimus).
• Grayson L, et al. Interaction between warfarin and cannabidiol — a case report. 2017. (classic documented case).
• FDA: Examples of drugs that interact with CYP enzymes and transporter systems — overview of clinically important CYP interactions and monitoring.
• Recent PK trial summarizing quantitative interaction potential with cannabis extracts (2023).

Cannabis & CBD Drug Interaction Reference Table