Tramadol

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: Tramadol

Examples of brand names: Tramal [DE]

ATC code: N02AX02

Main use (for orientation): Pain

Documented research summary

Small controlled single-dose study (12 completed): CBD 30 mg before amitriptyline 25 mg/tramadol 50 mg; tramadol Cmax ratio 1.10 (95% CI 0.99–1.22), no statistically established Cmax increase; do not extrapolate to chronic high-dose CBD. CBD/tramadol in a diabetic rat model showed additive, not synergistic, antinociception. Cannabis was common in tramadol seizure cases, but there was no isolated causal enhancement by cannabis. Coronary thrombus burden and renal calcium excretion in misuse cohorts are not controlled pharmacological pair-specific drug–drug interactions.

Uncertainties and limitations

Do not equate frequent co-use with causality. The M1/parent ratio and long-term safety are not resolved by the null Cmax finding; rare cannabinoids are insufficiently studied.

Separately recorded findings

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

CBD – clinically studied

Finding ID: B0036

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

Observation: Tramadol AUClast: LSM ratio 1.04 (95% CI 0.97–1.12; p=0.259), Cmax 1.10 (0.99–1.22; p=0.064). O-desmethyltramadol AUClast 0.99 (0.91–1.08; p=0.830), Cmax 1.05 (0.96–1.16; p=0.261). No statistically significant changes in these endpoints in the single-dose experiment.

Mechanism: Pharmacokinetics investigated

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: Null finding with limited evidential value

Limitations and uncertainties: Full-text Table 3 now also includes O-desmethyltramadol AUClast; no significant effect on this endpoint. Nortriptyline AUClast 1.06 (95% CI 0.94–1.18), Cmax 1.04 (0.91–1.18). Single fasted CBD dose with an amitriptyline/tramadol cocktail, not an assurance of long-term or general 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_D0146] TRAMADOL HYDROCHLORIDE TABLET, FILM COATED [UNICHEM PHARMACEUTICALS (USA), INC.]

Original source / bibliographic reference

Authors: Unichem Pharmaceuticals (USA), Inc.

Year: 2026

Source type: Current published human-use SPL / product information

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_37205869] Pharmacological Interaction Between Cannabidiol and Tramadol on Experimental Diabetic Neuropathic Pain: An Isobolographic Analysis.

Original source / bibliographic reference

Authors: Evans AA, Jesus CHA, Martins LL, Fukuyama AH, Gasparin AT, Crippa JA, Zuardi AW, Hallak JEC, Genaro K, de Castro Junior CJ, Zanoveli JM, Cunha JMD.

Year: 2024

Source type: Research Support, Non-U.S. Gov't; Journal Article

DOI: 10.1089/can.2021.0242

PMID: 37205869

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)

[CA_P_33122481] Cannabis and tramadol addiction: Do they imply additive risk for acute myocardial infarction in adults younger than 45 years?

Original source / bibliographic reference

Authors: Mansour H, Rayan M, Shnoda M, Kamal D.

Year: 2020

Source type: research-article; Journal Article

DOI: 10.14744/anatoljcardiol.2020.67206

PMID: 33122481

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)

[CA_P_30603010] Effect of tramadol addiction alone and its co-abuse with cannabis on urinary excretion of Copper, Zinc, and Calcium among Egyptian addicts.

Original source / bibliographic reference

Authors: El-Safty I, Eltamany E, Shouman A, El-Gamel O, Nada A, Ali W.

Year: 2018

Source type: research-article; Journal Article

DOI: 10.4314/ahs.v18i3.35

PMID: 30603010

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_35167199] Tramadol-Induced Acute Seizures: A Report of Three Cases.

Original source / bibliographic reference

Authors: Fawale MB, Adebowale AA, Idowu AO, Balogun SA, Sanusi AA, Komolafe MA.

Year: 2022

Source type: Journal Article; Case Reports

PMID: 35167199

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 direct article link could not be opened in the review tool; free full text is not assured.

Journal issue – article on pages 90–94

[CA_P_40747723] Prevalence and characteristics of tramadol-induced seizures in young adult emergency admissions.

Original source / bibliographic reference

Authors: Nielsen AVA, Lassen CK, Cakar D, Christensen J, Ingeman ML, Eiset AH, Sædder EA.

Year: 2025

Source type: Journal Article

DOI: 10.61409/a02250108

PMID: 40747723

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)

[CA_P_37652187] Modulatory effects of Cannabis sativa co-administration with tramadol and codeine on cognitive function in male rats.

Original source / bibliographic reference

Authors: Ademosun AO, Ajeigbe OF, Lawrence BO, Oboh G.

Year: 2023

Source type: Journal Article

DOI: 10.1016/j.neuro.2023.08.005

PMID: 37652187

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)

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