Ketoconazole

For an informed discussion with your doctor or pharmacist. This information collection is not a clinically validated interaction checker. Missing data do not establish safety. Do not change or stop prescribed medicines on the basis of this information. The findings apply to the specific conditions studied; laboratory and animal studies cannot be directly extrapolated to humans.

Active substance: Ketoconazole

Examples of brand names: Ketoconazole HRA [EU]

ATC code: J02AB02

Main use (for orientation): Fungal infections; Cushing's syndrome depending on product

Documented research summary

The human nabiximols study shows increased CBD/THC/11-OH-THC with ketoconazole; additional human liver microsome and animal studies establish metabolism, not clinical consequences for CBN/Delta8THC or the other 28 cannabinoids.

Uncertainties and limitations

Oral tablets; do not equate with topical preparations.

Shared enzymes must not be equated with clinical evidence of an interaction; CBD/THC findings cannot be extrapolated to other cannabinoids.

Separately recorded findings

2 separately recorded findings. Each statement applies to its documented study context.

CBD + Δ9-THC (nabiximols) – clinically investigated

Finding ID: B0043

Type of result: Positive finding / indication

Observation: Ketoconazole increased exposure after a single nabiximols dose. Geometric ratios, combination/alone, for THC, CBD and 11-OH-THC: Cmax 1.252/1.961/3.074; AUC0–t 1.770/2.715/3.823; AUC∞ 1.840/1.923/3.616. All associated 90% confidence intervals were above 1. With the combination, 11/11 people reported adverse events, mostly mild.

Mechanism: CYP3A inhibition

Study type: Randomised open-label phase I crossover pharmacokinetics

Context studied: 12 healthy men assigned; oral ketoconazole 400 mg once daily for five days in total (four pretreatment days plus co-administration on day five). A single four-spray oromucosal nabiximols dose = 10.8 mg THC plus 10 mg CBD. Paired Cmax/AUC0–t analysis n=11; AUC∞ n=10 for THC/11-OH-THC and n=9 for CBD.

Clinical interpretation: Possible; cannabinoid adverse effects

Limitations and uncertainties: Direction: ketoconazole → cannabinoids in the nabiximols mixture, not pure CBD or THC. Small group of healthy men; no formal power calculation. High variability and sometimes >20% extrapolated AUC∞; no general dose-adjustment rule or safety clearance.

Original sources for this finding: A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers [CL18]

CBD – laboratory and animal studies

Finding ID: B0173

Type of result: In vitro

Observation: CBD and 7-OH-CBD intrinsic clearance substantially reduced.

Mechanism: CYP3A4 inhibition control in human liver microsomes

Study type: Positive enzyme control in human liver microsomes

Context studied: 2026; antiseizure-medication mixtures and selective inhibitors; ketoconazole as a control substance.

Clinical interpretation: Laboratory finding, not a human interaction prediction or dose recommendation.

Limitations and uncertainties: Abstract read; clinical magnitude cannot be inferred outside specific human studies.

Original sources for this finding: Potential Role of CYP3A4 in Determining In Vivo Exposure to Cannabidiol (CBD) and its Active Metabolite 7-OH-CBD: Evidence from an In Vitro Study. [CA_P_42728549]

References and access status

[BWEB10] Ketoconazole tablets USP 200mg — Amerisyn LLC DailyMed

Original source / bibliographic reference

Authors: Amerisyn LLC

Year: 2026

Source type: Official US SPL

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

[CL18] A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers

Original source / bibliographic reference

Authors: Stott C; White L; Wright S; Wilbraham D; Guy G

Year: 2013

Source type: Randomised open-label phase I crossover study

DOI: 10.1186/2193-1801-2-236

PMID: 23750331

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

PubMed – bibliographic reference / abstract

DOI – publisher access (access restrictions may apply)

[BMED33381645] Nonlinear Disposition and Metabolic Interactions of Cannabidiol Through CYP3A Inhibition In Vivo in Rats.

Original source / bibliographic reference

Authors: Nagao M, Nakano Y, Tajima M, Sugiyama E, Sato VH, Inada M, Sato H.

Year: 2020

Source type: Primary publication; abstract reviewed

DOI: 10.1089/can.2019.0098

PMID: 33381645

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

PubMed – bibliographic reference / abstract

PubMed Central – archived text

DOI – publisher access (access restrictions may apply)

[CA_P_42728549] Potential Role of CYP3A4 in Determining In Vivo Exposure to Cannabidiol (CBD) and its Active Metabolite 7-OH-CBD: Evidence from an In Vitro Study.

Original source / bibliographic reference

Authors: Jaisupa N, Birgersson S, Ashton M.

Year: 2026

Source type: Journal Article

DOI: 10.1007/s13318-026-01032-y

PMID: 42728549

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[BMED17303175] Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes.

Original source / bibliographic reference

Authors: Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I.

Year: 2007

Source type: Publication; title and abstract reviewed

DOI: 10.1016/j.lfs.2006.12.032

PMID: 17303175

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

PubMed – bibliographic reference / abstract

DOI – publisher access (access restrictions may apply)

[BMED21704641] Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes.

Original source / bibliographic reference

Authors: Jiang R, Yamaori S, Takeda S, Yamamoto I, Watanabe K.

Year: 2011

Source type: Publication; title and abstract reviewed

DOI: 10.1016/j.lfs.2011.05.018

PMID: 21704641

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

PubMed – bibliographic reference / abstract

DOI – publisher access (access restrictions may apply)

[BMED11038155] CYP3A4 is a major isoform responsible for oxidation of 7-hydroxy-Delta(8)-tetrahydrocannabinol to 7-oxo-delta(8)-tetrahydrocannabinol in human liver microsomes.

Original source / bibliographic reference

Authors: Matsunaga T, Kishi N, Higuchi S, Watanabe K, Ohshima T, Yamamoto I.

Year: 2000

Source type: Publication; title and abstract reviewed

PMID: 11038155

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

PubMed – bibliographic reference / abstract

Research as of 23 October 2026. Not all original full texts could be reviewed in full. Source accessibility and the strength of scientific evidence must be assessed separately. An accessible link does not establish medical approval; a bibliographic record with an abstract does not replace the original full text.

Drug search and explanation of the evidence · Guide: cannabinoids and medicines · Author and responsibility