01
CBD Pharmacokinetic Interactions
CYP3A4 and CYP2C19 inhibitor
CBD as Perpetrator
CBD inhibits CYP3A4 and CYP2C19, increasing levels of co-administered drugs metabolised by these enzymes
Drug / Class
Mechanism
Clinical Effect
Severity
Action Required
Clobazam
CYP3A4 + CYP2C19 inhibition
Increased N-desmethylclobazam levels (up to 5-fold)
red
Reduce clobazam dose by 50%. TDM recommended. Somnolence risk.
Clobazamred
Valproate
UGT pathway + hepatic PD
Additive hepatotoxicity; transaminase elevations
red
Mandatory baseline and periodic LFTs per Epidyolex labelling.
Valproatered
Warfarin
CYP2C19 inhibition
Increased INR; enhanced anticoagulant effect
red
Close INR monitoring at initiation and dose changes. Dose reduction likely.
Warfarinred
SSRIs (sertraline, citalopram)
CYP2C19 inhibition
Increased SSRI exposure
amber
Monitor for serotonergic effects. Consider dose reduction.
SSRIs (sertraline, citalopram)amber
Midazolam / benzodiazepines
CYP3A4 inhibition
Increased sedation and respiratory depression risk
amber
Reduce benzodiazepine dose. Monitor sedation levels.
Midazolam / benzodiazepinesamber
Tacrolimus / everolimus
CYP3A4 inhibition
Increased immunosuppressant levels
red
TDM mandatory. Dose reduction required. Nephrotoxicity risk.
Tacrolimus / everolimusred
Phenytoin
CYP2C19 inhibition
Increased phenytoin levels; toxicity risk
amber
TDM recommended. Monitor for ataxia, nystagmus.
Phenytoinamber
Rifampicin
CYP3A4 induction
Reduced CBD levels
amber
CBD efficacy may be reduced. Consider dose increase or alternative.
Rifampicinamber
02
THC Pharmacokinetic and Pharmacodynamic Interactions
CYP3A4 substrate + CNS depressant
THC as Victim and PD Interactions
THC is a CYP3A4 substrate (levels affected by inhibitors/inducers) and has additive CNS/cardiovascular effects
Drug / Class
Mechanism
Clinical Effect
Severity
Action Required
Ketoconazole / ritonavir
CYP3A4 inhibition
Increased THC exposure; enhanced CNS effects
red
Avoid combination or reduce THC dose significantly. Monitor CNS effects.
Ketoconazole / ritonavirred
Clarithromycin / erythromycin
CYP3A4 inhibition
Increased THC levels
amber
Monitor for increased psychoactive effects. Consider dose reduction.
Clarithromycin / erythromycinamber
Rifampicin
CYP3A4 induction
Reduced THC levels; loss of efficacy
amber
THC efficacy may be significantly reduced. Consider alternative.
Rifampicinamber
Carbamazepine / phenytoin
CYP3A4 induction
Reduced THC levels
amber
Monitor for reduced efficacy. Dose adjustment may be needed.
Carbamazepine / phenytoinamber
Warfarin
Unknown (possibly CYP-mediated)
Increased INR
red
Close INR monitoring. Enhanced anticoagulant effect documented.
Warfarinred
Opioids
Pharmacodynamic
Additive sedation and respiratory depression
red
Reduce opioid dose. Monitor respiratory function. Patient counselling.
Opioidsred
Benzodiazepines / gabapentinoids
Pharmacodynamic
Additive CNS depression
red
Dose reduction of CNS depressant. Monitor sedation and falls risk.
Benzodiazepines / gabapentinoidsred
Alcohol
Pharmacodynamic
Additive impairment; increased THC absorption
red
Advise abstinence or strict moderation. Driving risk.
Alcoholred
Sympathomimetics
Pharmacodynamic
Additive tachycardia and hypertension
amber
Caution in cardiovascular-risk patients. Monitor HR and BP.
Sympathomimeticsamber
Sources
Epidyolex SmPC, Sativex SmPC, Cesamet SmPC, Whiting PF et al. JAMA 2015, BNF Interactions Checker. All interactions require independent verification. This reference is non-promotional and does not constitute medical advice.