Tolbutamide

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: Tolbutamide

Examples of brand names: Orinase [USA; historical example]

ATC code: A10BB03

Main use (for orientation): Type 2 diabetes; CYP probe substance

Documented research summary

Tolbutamide used as a CYP2C9 probe substrate in several laboratory studies. In the 2023 human-liver-microsome paper, pure CBD/THC and characterised extracts inhibit tolbutamide hydroxylation; a CBG extract is not a pure-CBG experiment. Clinical hypoglycaemia/AUC not measured.

Uncertainties and limitations

Methods/results/discussion of PMC9940649 read. Do not add substrate-dependent extract effects linearly.

Retain existing ME01 tolbutamide rows as laboratory probe substrates; do not present them as clinical findings.

Separately recorded findings

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

CBD – clinically studied

Finding ID: B0005

Type of result: No / minor effect under the conditions studied

Observation: No exposure change measured.

Mechanism: CYP2C9 probe

Study type: Human pharmacokinetics according to product information

Context studied: CBD 7.5 mg/kg twice daily; tolbutamide 500 mg; n not stated.

Clinical interpretation: No relevant pharmacokinetic signal with this regimen

Limitations and uncertainties: Not safety evidence for all CYP2C9 substrates.

Original sources for this finding: EPIDIOLEX (cannabidiol) oral solution – US Prescribing Information, revised 5/2026 [V5_US_LABEL_2026]; EPIDIOLEX (cannabidiol) oral solution – Prescribing Information, revised 6/2025 [CL02]

CBDA – laboratory and animal studies

Finding ID: B0121

Type of result: Context-specific finding; read the limitations

Observation: Apparent IC50 0.4 µM.

Mechanism: CYP2C9 inhibition

Study type: Laboratory measurement: recombinant CYP2C9 probe-substrate assay

Context studied: Tolbutamide exclusively as a CYP2C9 probe substrate in the laboratory; not a patient experiment or prediction of a tolbutamide–cannabinoid interaction.

Clinical interpretation: Not a drug-interaction prediction; enzyme probe-substrate measurement only

Limitations and uncertainties: Apparent IC50 is a laboratory parameter, not a clinical risk measure; neither a demonstrated nor modelled tolbutamide interaction. Do not present as an antidiabetic drug-interaction prediction.

Original sources for this finding: Cannabinoid Interactions with Cytochrome P450 Drug Metabolism: a Full-Spectrum Characterization [ME01]

CBDV – laboratory and animal studies

Finding ID: B0122

Type of result: Context-specific finding; read the limitations

Observation: Apparent IC50 4.3 µM.

Mechanism: CYP2C9 inhibition

Study type: Laboratory measurement: recombinant CYP2C9 probe-substrate assay

Context studied: Tolbutamide exclusively as a CYP2C9 probe substrate in the laboratory; not a patient experiment or prediction of a tolbutamide–cannabinoid interaction.

Clinical interpretation: Not a drug-interaction prediction; enzyme probe-substrate measurement only

Limitations and uncertainties: Apparent IC50 is a laboratory parameter, not a clinical risk measure; neither a demonstrated nor modelled tolbutamide interaction. Do not present as an antidiabetic drug-interaction prediction.

Original sources for this finding: Cannabinoid Interactions with Cytochrome P450 Drug Metabolism: a Full-Spectrum Characterization [ME01]

CBDVA – laboratory and animal studies

Finding ID: B0123

Type of result: Context-specific finding; read the limitations

Observation: Apparent IC50 1.3 µM.

Mechanism: CYP2C9 inhibition

Study type: Laboratory measurement: recombinant CYP2C9 probe-substrate assay

Context studied: Tolbutamide exclusively as a CYP2C9 probe substrate in the laboratory; not a patient experiment or prediction of a tolbutamide–cannabinoid interaction.

Clinical interpretation: Not a drug-interaction prediction; enzyme probe-substrate measurement only

Limitations and uncertainties: Apparent IC50 is a laboratory parameter, not a clinical risk measure; neither a demonstrated nor modelled tolbutamide interaction. Do not present as an antidiabetic drug-interaction prediction.

Original sources for this finding: Cannabinoid Interactions with Cytochrome P450 Drug Metabolism: a Full-Spectrum Characterization [ME01]

CBG – laboratory and animal studies

Finding ID: B0124

Type of result: Context-specific finding; read the limitations

Observation: Apparent IC50 1.0 µM.

Mechanism: CYP2C9 inhibition

Study type: Laboratory measurement: recombinant CYP2C9 probe-substrate assay

Context studied: Tolbutamide exclusively as a CYP2C9 probe substrate in the laboratory; not a patient experiment or prediction of a tolbutamide–cannabinoid interaction.

Clinical interpretation: Not a drug-interaction prediction; enzyme probe-substrate measurement only

Limitations and uncertainties: Apparent IC50 is a laboratory parameter, not a clinical risk measure; neither a demonstrated nor modelled tolbutamide interaction. Do not present as an antidiabetic drug-interaction prediction.

Original sources for this finding: Cannabinoid Interactions with Cytochrome P450 Drug Metabolism: a Full-Spectrum Characterization [ME01]

CBGA – laboratory and animal studies

Finding ID: B0125

Type of result: Context-specific finding; read the limitations

Observation: Apparent IC50 6.4 µM.

Mechanism: CYP2C9 inhibition

Study type: Laboratory measurement: recombinant CYP2C9 probe-substrate assay

Context studied: Tolbutamide exclusively as a CYP2C9 probe substrate in the laboratory; not a patient experiment or prediction of a tolbutamide–cannabinoid interaction.

Clinical interpretation: Not a drug-interaction prediction; enzyme probe-substrate measurement only

Limitations and uncertainties: Apparent IC50 is a laboratory parameter, not a clinical risk measure; neither a demonstrated nor modelled tolbutamide interaction. Do not present as an antidiabetic drug-interaction prediction.

Original sources for this finding: Cannabinoid Interactions with Cytochrome P450 Drug Metabolism: a Full-Spectrum Characterization [ME01]

THCVA – laboratory and animal studies

Finding ID: B0126

Type of result: Context-specific finding; read the limitations

Observation: Apparent IC50 4.0 µM.

Mechanism: CYP2C9 inhibition

Study type: Laboratory measurement: recombinant CYP2C9 probe-substrate assay

Context studied: Tolbutamide exclusively as a CYP2C9 probe substrate in the laboratory; not a patient experiment or prediction of a tolbutamide–cannabinoid interaction.

Clinical interpretation: Not a drug-interaction prediction; enzyme probe-substrate measurement only

Limitations and uncertainties: Apparent IC50 is a laboratory parameter, not a clinical risk measure; neither a demonstrated nor modelled tolbutamide interaction. Do not present as an antidiabetic drug-interaction prediction.

Original sources for this finding: Cannabinoid Interactions with Cytochrome P450 Drug Metabolism: a Full-Spectrum Characterization [ME01]

CBN – laboratory and animal studies

Finding ID: B0127

Type of result: Context-specific finding; read the limitations

Observation: No effect in the tolbutamide assay assessed.

Mechanism: CYP2C9 assessment

Study type: Laboratory measurement: recombinant CYP2C9 probe-substrate assay; no effect

Context studied: Tolbutamide exclusively as a CYP2C9 probe substrate in the laboratory; not a patient experiment or prediction of a tolbutamide–cannabinoid interaction.

Clinical interpretation: Not a drug-interaction prediction; enzyme probe-substrate measurement only

Limitations and uncertainties: Substrate-dependent negative laboratory result. Other CYP2C9 substrates in ME02 were inhibited; no general assurance of safety or clinical interaction prediction.

Original sources for this finding: Cannabinoid Interactions with Cytochrome P450 Drug Metabolism: a Full-Spectrum Characterization [ME01]

CBD – laboratory and animal studies

Finding ID: B0399

Type of result: Laboratory probe-substrate finding

Observation: Inhibition of tolbutamide hydroxylation; reported IC50 for pure CBD 0.76 µM or THC 0.081 µM.

Mechanism: CYP2C9 probe-substrate hydroxylation

Study type: Pooled human liver microsomes

Context studied: Tolbutamide 100 µM; human liver microsomes from 150 donors. Pure substances and several characterised extracts tested separately.

Clinical interpretation: Interpret within the stated study context; no independent dosage or treatment recommendation.

Limitations and uncertainties: Probe substrate, not a clinical tolbutamide interaction or glucose measurement. Substrate-dependent extract effects; CBG extract is not pure CBG.

Original sources for this finding: Phytochemical Comparison of Medicinal Cannabis Extracts and Study of Their CYP-Mediated Interactions with Coumarinic Oral Anticoagulants. [CA_P_36814687]

THC – laboratory and animal studies

Finding ID: B0400

Type of result: Laboratory probe-substrate finding

Observation: Inhibition of tolbutamide hydroxylation; reported IC50 for pure CBD 0.76 µM or THC 0.081 µM.

Mechanism: CYP2C9 probe-substrate hydroxylation

Study type: Pooled human liver microsomes

Context studied: Tolbutamide 100 µM; human liver microsomes from 150 donors. Pure substances and several characterised extracts tested separately.

Clinical interpretation: Interpret within the stated study context; no independent dosage or treatment recommendation.

Limitations and uncertainties: Probe substrate, not a clinical tolbutamide interaction or glucose measurement. Substrate-dependent extract effects; CBG extract is not pure CBG.

Original sources for this finding: Phytochemical Comparison of Medicinal Cannabis Extracts and Study of Their CYP-Mediated Interactions with Coumarinic Oral Anticoagulants. [CA_P_36814687]

References and access status

[RLABEL_D0246] Tolbutamide Tablets – Summary of Product Characteristics,15.01.2026

Original source / bibliographic reference

Authors: Regulatory product information; respective marketing authorisation holder

Year: 2026

Source type: Product information / SmPC / US Prescribing Information

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

Bibliographic attribution or source identity cross-checked.

[CA_P_36814687] Phytochemical Comparison of Medicinal Cannabis Extracts and Study of Their CYP-Mediated Interactions with Coumarinic Oral Anticoagulants.

Original source / bibliographic reference

Authors: Treyer A, Reinhardt JK, Eigenmann DE, Oufir M, Hamburger M.

Year: 2023

Source type: research-article; Journal Article

DOI: 10.1159/000528465

PMID: 36814687

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)

PubMed Central – full-text access according to the literature database – Archive attribution confirmed by Europe PMC metadata. Direct retrieval was not fully verified here; access may require a browser check.

Europe PMC – full-text access according to the literature database – Listed as freely available HTML full text in the official Europe PMC metadata. Direct retrieval was not fully verified here.

[V5_US_LABEL_2026] EPIDIOLEX (cannabidiol) oral solution – US Prescribing Information, revised 5/2026

Original source / bibliographic reference

Authors: Jazz Pharmaceuticals, Inc. / DailyMed

Year: 2026

Source type: Regulatory US product information; not an additional independent clinical study

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

Bibliographic attribution or source identity cross-checked.

[CL02] EPIDIOLEX (cannabidiol) oral solution – Prescribing Information, revised 6/2025

Original source / bibliographic reference

Authors: FDA / Jazz Pharmaceuticals

Year: 2025

Source type: Regulatory product information

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

Bibliographic attribution or source identity cross-checked.

[ME01] Cannabinoid Interactions with Cytochrome P450 Drug Metabolism: a Full-Spectrum Characterization

Original source / bibliographic reference

Authors: Doohan PT; Oldfield LD; Arnold JC; Anderson LL

Year: 2021

Source type: Original study: recombinant CYP assays

DOI: 10.1208/s12248-021-00616-7

PMID: 34181150

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

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