Amitriptyline

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: Amitriptyline

Examples of brand names: Saroten [DE]

ATC code: N06AA09

Main use (for orientation): Depression; neuropathic pain

Documented research summary

A single 30 mg CBD dose before amitriptyline 25 mg plus tramadol 50 mg increased amitriptyline AUC0–24 by 13% and Cmax by 17% in CL12. No evidence of an equally large change with chronic high doses. A new overdose case involving cannabis is highly confounded and is not quantitative interaction evidence.

Uncertainties and limitations

2026 overdose of approximately 750 mg amitriptyline, obesity and unknown genotype: cannabinoid contribution speculative. Do not confuse nortriptyline as a metabolite with direct nortriptyline administration.

Separately recorded findings

1 separately recorded finding. Each statement applies to its documented study context.

CBD – clinically studied

Finding ID: B0035

Type of result: Positive finding / indication

Observation: Amitriptyline AUClast with sampling up to 24 hours: least-squares mean ratio 1.13 (95% CI 1.01–1.26; p=0.033); Cmax 1.17 (1.01–1.36; p=0.041). Do not present as AUC∞.

Mechanism: CYP inhibition plausible; isoenzyme contribution not established

Study type: Open-label crossover pharmacokinetics

Context studied: Open-label fixed sequence, 13 healthy adults enrolled/dosed, 12 completed. Day 1: amitriptyline 25 mg and tramadol 50 mg given simultaneously; after at least seven days of washout, a single dose of CBD oil 30 mg (Clinican, 10% in almond oil) one hour before the same combined medicine administration. Fasted; samples up to 24 h.

Clinical interpretation: Small effect; clinical significance unclear

Limitations and uncertainties: Single CBD dose under fasting conditions; both medicines together. AUClast/AUC0–24h does not cover total terminal amitriptyline/nortriptyline exposure. CYP2D6/CYP2C19/CYP3A4 poor metabolisers and CYP2D6 ultrarapid metabolisers excluded. No blanket confirmation of safety.

Original sources for this finding: Low-dose cannabidiol increases plasma concentrations of amitriptyline: A clinical drug-drug interaction study [CL12]

References and access status

[CA_L_D0096] Amitriptyline 10mg Film-Coated Tablets – SmPC

Original source / bibliographic reference

Authors: Brown & Burk UK Ltd

Year: 2026

Source type: Official manufacturer's SmPC (eMC)

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

Bibliographic attribution or source identity cross-checked.

[CL12] Low-dose cannabidiol increases plasma concentrations of amitriptyline: A clinical drug-drug interaction study

Original source / bibliographic reference

Authors: Gorbenko AA; Post TE; Strugala PK; Klaassen ES; Klumpers LE; de Visser SJ; Sempio C; Klawitter J; Heuberger JAAC; Groeneveld GJ

Year: 2026

Source type: Open-label crossover study with a fixed sequence

DOI: 10.1002/bcp.70415

PMID: 41398552

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.

[CA_P_42583662] Prolonged Tricyclic Antidepressant Toxicity in a Pediatric Patient: The Importance of Understanding the Multifactorial Nature of Amitriptyline Metabolism.

Original source / bibliographic reference

Authors: Navarro AW, Sahhar H.

Year: 2026

Source type: Journal Article; Case Reports; case-report

DOI: 10.7759/cureus.112541

PMID: 42583662

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.

[CA_P_38129125] Assessing Dose- and Sex-Dependent Antinociceptive Effects of Cannabidiol and Amitriptyline, Alone and in Combination, and Exploring Mechanism of Action Involving Serotonin 1A Receptors.

Original source / bibliographic reference

Authors: Barnes RC, Banjara S, McHann MC, Almodovar S, Henderson-Redmond AN, Morgan DJ, Castro-Piedras I, Guindon J.

Year: 2024

Source type: Research Support, Non-U.S. Gov't; research-article; Journal Article; Research Support, N.I.H., Extramural

DOI: 10.1124/jpet.123.001855

PMID: 38129125

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.

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