Ethosuximide

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: Ethosuximide

Examples of brand names: Petnidan [DE]

ATC code: N03AD01

Main use (for orientation): Absence epilepsy

Documented research summary

A small uncontrolled human pilot shows a signal in three CBD plus ethosuximide patients; an older rat experiment reports reduced ethosuximide potency with CBD. Different designs and unestablished mechanisms support neither a clinical synergy claim nor a general antagonism rule. The already fully read Gaston 2023 expanded-access programme (CL20/PMC10690661) found no statistical concentration signal in 9 exposed people (p=0.8956); small sample, not equivalence or safety evidence.

Uncertainties and limitations

Does not establish safety for less-studied cannabinoids or untested formulations/doses.

Do not infer clinical dosage from preclinical effects or enzyme hypotheses.

Separately recorded findings

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

CBD – clinical signals

Finding ID: B0061

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

Observation: No concentration signal; p=0.8956.

Mechanism: PK observation

Study type: Observational study: no signal detected

Context studied: n=9.

Clinical interpretation: Not ruled out

Limitations and uncertainties: Context / limitations of CL20; a lack of statistical significance does not establish equivalence.

Original sources for this finding: Final analysis of potential drug-drug interactions between highly purified cannabidiol and anti-seizure medications in an open-label expanded access program [CL20]

CBD – clinical signals

Finding ID: B0342

Type of result: Clinical signal

Observation: All three patients concurrently treated with ethosuximide belonged to the group with reduced spike-and-wave complexes.

Mechanism: Combination effect; mechanism not isolated

Study type: Uncontrolled human pilot, n=14

Context studied: 90 days of pharmaceutical CBD; overall 9/14 had increased and 5/14 decreased EEG burden; the three combination cases partly received other antiseizure medicines.

Clinical interpretation: No individual dose or treatment recommendation.

Limitations and uncertainties: Abstract only; tiny non-randomised subgroup, not proof of a favourable interaction.

Original sources for this finding: Efficacy of highly purified cannabidiol (CBD) in typical absence seizures: A pilot study. [C_PR_37980860]

CBD – laboratory and animal studies

Finding ID: B0343

Type of result: Preclinical evidence

Observation: CBD reduced the anticonvulsant potency of ethosuximide.

Mechanism: Combination effect; mechanism not isolated

Study type: Rat experiment

Context studied: Oral substances at peak effect; electroshock/audiogenic tests and other antiseizure-medication combinations.

Clinical interpretation: No individual dose or treatment recommendation.

Limitations and uncertainties: Abstract only; precise individual model/dose details absent; do not extrapolate to humans.

Original sources for this finding: Cannabidiol--antiepileptic drug comparisons and interactions in experimentally induced seizures in rats. [C_PR_850145]

THC – laboratory and animal studies

Finding ID: B0344

Type of result: Preclinical evidence

Observation: Ethosuximide blocked THC-induced seizures only at toxic doses.

Mechanism: Combination effect; mechanism not isolated

Study type: Rabbit experiment

Context studied: Specifically susceptible New Zealand White population, psychoactive Δ9-THC as the seizure trigger.

Clinical interpretation: No individual dose or treatment recommendation.

Limitations and uncertainties: Original abstract assessed; original full text remains unverified. Group sizes, specific exposures, toxicity criteria and complete statistics therefore remain unresolved. Special THC seizure model in rabbits, not evidence of a therapeutic combination effect or safe use in humans.

Original sources for this finding: Anticonvulsant drug antagonism of delta9tetrahydrocannabinol-induced seizures in rabbits. [C_PR_841172]

References and access status

[C_LABEL_D0058] ZARONTIN (ETHOSUXIMIDE) CAPSULE [PARKE-DAVIS DIV OF PFIZER INC]

Original source / bibliographic reference

Authors: PARKE-DAVIS DIV OF PFIZER INC

Year: 2026

Source type: US Structured Product Label

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

Bibliographic attribution or source identity cross-checked.

[C_LABEL_D0058_UK] Ethosuximide neuraxpharm 250 mg soft capsules – SmPC

Original source / bibliographic reference

Authors: Neuraxpharm UK Ltd

Year: 2026

Source type: UK SmPC

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

Bibliographic attribution or source identity cross-checked.

[C_PR_37980860] Efficacy of highly purified cannabidiol (CBD) in typical absence seizures: A pilot study.

Original source / bibliographic reference

Authors: Azevedo M, Benbadis SR.

Year: 2023

Source type: Primary source, abstract read

DOI: 10.1016/j.yebeh.2023.109512

PMID: 37980860

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

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[C_PR_850145] Cannabidiol--antiepileptic drug comparisons and interactions in experimentally induced seizures in rats.

Original source / bibliographic reference

Authors: Consroe P, Wolkin A.

Year: 1977

Source type: Primary source, abstract read

DOI: 10.1016/s0022-3565(25)30824-4

PMID: 850145

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)

[C_PR_841172] Anticonvulsant drug antagonism of delta9tetrahydrocannabinol-induced seizures in rabbits.

Original source / bibliographic reference

Authors: Consroe P, Martin P, Eisenstein D.

Year: 1977

Source type: Rabbit experiment; original abstract assessed, original full text not verified

PMID: 841172

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

Bibliographic attribution or source identity cross-checked.

Unresolved access questions / further review: The official original abstract was reassessed scientifically on 23 October 2026. The ethosuximide finding agrees with it, but remains limited to a special THC seizure model in rabbits. Europe PMC access provides bibliographic data and abstract, not full text. Sample size, specific exposures, toxicity criteria and complete statistics remain unassessed.

Europe PMC – bibliographic data and abstract (JSON; not full text) – Official bibliographic record successfully checked. The view is machine-readable and is not the original full text.

[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)

[CL20] Final analysis of potential drug-drug interactions between highly purified cannabidiol and anti-seizure medications in an open-label expanded access program

Original source / bibliographic reference

Authors: Gaston TE; Bebin EM; Cutter GR; Grayson L; Szaflarski JP

Year: 2023

Source type: Open-label longitudinal observational study

DOI: 10.1002/epi4.12815

PMID: 37593907

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)

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.

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