CBD/THC drug interactions

Metabolism and clearance	Enzyme or efflux transporter inhibition or induction	Half-life (hours)	Pharmacokinetic interactions
CBD (pharmaceutical and standardized extract)*^[1,2]
Hepatic and gut metabolism via CYP2C19 (minor), CYP3A4 (major), glucuronidation (UGT1A7, UGT1A9, and UGT2B7) to active metabolite (7-OH-CBD) and inactive metabolite (7-COOH-CBD) Metabolites cleared in feces (primarily) and urine (minor)	Inhibits: CYP2C19 (moderate), CYP1A2 (weak), CYP2C9 (weak), CYP3A4 (weak), P-gp/ABCB1, BSEP/ABCB11	56 to 61	Potential for CBD to affect other medications
			CBD can increase serum concentrations, clinical effects, and toxicity of substrates of CYP2C19, CYP2C9, CYP1A2, CYP3A4, and P-gp (examples):
			Cilostazol Citalopram Clobazam Colchicine	Cyclosporine Dabigatran Digoxin Doxorubicin Phenytoin	Sirolimus Tacrolimus Tizanidine Vincristine Warfarin
			Potential for CBD to be affected by other medications
			Serum concentrations, clinical effects, and toxicity of CBD can increase if coadministered with CYP3A4 inhibitors (examples):^¶
			Clarithromycin Cobicistat and combinations	Itraconazole Ombitasvir combinations Posaconazole	Ritonavir combinations (eg, nirmatrelvir-ritonavir [Paxlovid])
			Serum concentrations and clinical effects of CBD can decrease if coadministered with CYP3A4 and/or CYP2C19 inducers (examples):^¶
			Carbamazepine	Phenobarbital	Rifampin
Cannabis (pharmaceutical THC and CBD)^Δ^[3]
Hepatic metabolism via CYP2C9 (major), 2C19 (minor), 2D6 (minor), and 3A4 (major), glucuronidation (UGT1A7, UGT1A9, and UGT2B7) to active metabolites (11-OH-THC, 7-OH-CBD) and oxidation to inactive metabolite (11-nor-9-COOH-THC, 7-COOH-CBD) Metabolites are cleared in feces (primarily) and urine (minor)	Preliminary in vitro data provided in the manufacturer's labeling suggest the possibility of metabolic inhibitory or induction effects, but clinical relevance is largely unconfirmed.^◊ In a pharmacokinetic study, THC extract alone did not alter CYP metabolism^[2].	24 to 36 (or longer)	Potential for cannabis to affect other medications
			Warfarin: Cannabis may increase INR values (by CBD inhibition of CYP2C9)	Cannabis may decrease efficacy of hormonal contraceptives according to product label^[3]; however, actual risk of contraceptive failure has not been adequately studied
			Potential for cannabis to be affected by other medications
			Serum concentrations, clinical effects, and toxicity of cannabis can increase if coadministered with CYP3A4 and/or 2C9 inhibitors (examples):^¶
			Clarithromycin Cobicistat and combinations	Fluconazole Ombitasvir combinations	Posaconazole Ritonavir combinations (eg, nirmatrelvir-ritonavir [Paxlovid])
			Serum concentrations and clinical effects of cannabis can decrease if coadministered with strong CYP3A4 inducers (examples):^¶
			Carbamazepine	Phenobarbital	Rifampin

NOTE: Examples of drug interactions are for illustrative purposes; many other interactions can occur. Specific interactions may warrant dose adjustment or avoidance of some combinations. Additive or antagonistic interactions (eg, additive sedation with opioids, alcohol, sedatives) are not addressed in this table. To determine a full set of potential interactions for a specific patient's medication list, use the Lexicomp drug interactions program included within UpToDate.

CYP, UGT, and P-gp classifications are based on US Food and Drug Administration guidance^[4,5]. Other sources may use a different classification system, resulting in some agents being classified differently.

CBD: cannabidiol; THC: tetrahydrocannabinol; CYP: cytochrome P450; UGT: uridine 5'-diphospho-glucuronosyltransferase; 7-OH-CBD: 7-hydroxycannabidiol; 7-COOH-CBD: 7-carboxy-cannabidiol; P-gp: P-glycoprotein drug efflux pump; BSEP: bile salt export pump; INR: international normalized ratio; 11-OH-THC: 11-hydroxytetrahydrocannabinol; 11-nor-9-COOH-THC: 11-nor-9-carboxytetrahydrocannabinol.

* CBD data are derived mainly from labeling for an orally administered pharmaceutical antiseizure drug^[1] and results of a pharmacokinetic study of an orally administered CBD extract containing a trace amount of THC^[2]. Other nonpharmaceutical CBD products (eg, herbal oils, gummies, etc) can vary widely in potency and are administered by other routes, which can variably alter metabolic effects and potential for interactions.

¶ Lists of strong and moderate CYP3A inhibitors and inducers are available as a separate table in UpToDate.

Δ Cannabis data are derived mainly from labeling for standardized THC-CBD (Sativex)^[3] administered as an oromucosal spray and a pharmacokinetic study of cannabis extracts^[2]. Other cannabis preparations and herbal products have different constituent potencies and are administered by other routes (inhaled, ingested, etc), which can variably alter metabolic effects and potential for interactions.

◊ According to the THC-CBD (Sativex) product monograph^[3] (Canada), in vitro data suggest cannabis components may inhibit CYP3A4 and UGT glucuronidation and/or induce CYP1A2, 2B6, and 3A4. The labeling advises a regimen review if administered with sensitive (eg, narrow therapeutic margin) substrates. These potential interactions have not yet been confirmed by adequate pharmacokinetic or clinical data.

References:

Cannabidiol (Epidiolex) US prescribing information (January, 2023); US NLM DailyMed. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8bf27097-4870-43fb-94f0-f3d0871d1eec (Accessed May 9, 2023).
Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of cytochrome P450-mediated cannabinoid-drug interactions in healthy adult participants. Clin Pharmacol Ther 2023; 114:693.
Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) (Sativex) (December, 2019) Canada Product Monograph; Health Canada. Available at: https://pdf.hres.ca/dpd_pm/00054388.PDF (Accessed May 9, 2023).
Clinical drug interaction studies – Cytochrome P450 enzyme- and transporter-mediated drug interactions guidance for industry, January 2020. US Food and Drug Administration. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-drug-interaction-studies-cytochrome-p450-enzyme-and-transporter-mediated-drug-interactions (Accessed May 9, 2023).
Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers, August 2022. US Food and Drug Administration. Available at: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers (Accessed May 9, 2023).

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CBD/THC drug interactions