Evidence map›Paper›PMID 41398552›Full record

ArticleBritish journal of clinical pharmacology2026

Low-dose cannabidiol increases plasma concentrations of amitriptyline: A clinical drug-drug interaction study.

Andriy A Gorbenko, Titiaan E Post, Pamela K Strugala, Erica S Klaassen, Linda E Klumpers, Saco J de Visser, Cristina Sempio, Jost Klawitter, Jules A A C Heuberger, Geert J Groeneveld

Abstract read
In one paragraph

Article in British journal of clinical pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Andriy A GorbenkoCentre for Human Drug Research, Leiden, The Netherlands.ORCID https://orcid.org/0000-0001-5917-7888
Titiaan E PostCentre for Human Drug Research, Leiden, The Netherlands.ORCID https://orcid.org/0000-0002-4844-6402
Pamela K StrugalaCentre for Human Drug Research, Leiden, The Netherlands.ORCID https://orcid.org/0009-0008-2525-2323
Erica S KlaassenCentre for Human Drug Research, Leiden, The Netherlands.ORCID https://orcid.org/0000-0003-0089-1846
Linda E KlumpersVerdient Science, LLC., Denver, CO, USA.ORCID https://orcid.org/0000-0003-3453-9744
Saco J de VisserCentre for Future Affordable and Sustainable Therapy development (FAST), the Hague, the Netherlands.ORCID https://orcid.org/0000-0003-3649-5714
Cristina SempioDepartment of Anesthesiology, University of Colorado, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0002-8095-612X
Jost KlawitterDepartment of Anesthesiology, University of Colorado, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0002-6413-4820
Jules A A C HeubergerCentre for Human Drug Research, Leiden, The Netherlands.ORCID https://orcid.org/0000-0001-7202-5088
Geert J GroeneveldCentre for Human Drug Research, Leiden, The Netherlands.ORCID https://orcid.org/0000-0002-4655-6667

Funding

ZonMw 848120001
6 · The paper itself

Abstract

aimsCannabidiol (CBD), the main non-intoxicating compound from the cannabis plant, is regularly used by patients with chronic pain who also take analgesics. CBD has previously been shown to inhibit CYP-mediated drug metabolism. This study aimed to characterize the potential pharmacokinetic interaction of CBD with amitriptyline and tramadol, two commonly used analgesics.

methodsThis was an open-label, fixed-sequence, 2-way crossover study in 13 healthy participants. On Day 1, 25 mg amitriptyline and 50 mg tramadol were co-administered orally in a fasted condition, followed by a 7-day washout period. On Day 8, 30 mg CBD was administered orally 1 h prior to amitriptyline and tramadol. Pharmacokinetic sampling was performed for CBD, amitriptyline, tramadol and their respective active metabolites nortriptyline and O-desmethyltramadol for up to 24 h post-dose. The areas under the curve (AUCs) were compared between visits using a mixed effects model.

resultsTwelve participants (4M/8F) completed the study; one participant (M) dropped out for personal reasons. CBD significantly increased the AUC

conclusionsA single dose of 30 mg CBD significantly influenced the metabolism of amitriptyline in healthy volunteers. In patients, CBD-induced drug interactions may be more pronounced in chronic dosing and dependent upon prandial status.

Indexed as

AmitriptylineCannabidiolAdultAnalgesics, OpioidArea Under CurveCross-Over StudiesDrug InteractionsFemaleHealthy VolunteersHumansMaleMiddle AgedNortriptylineTramadolYoung AdultAmitriptylineAnalgesics, OpioidCannabidiolNortriptylineO-demethyltramadolTramadolamitriptylinecannabidiolCBDCYP2C19DDIinteractiontramadol

Identifiers

PMID41398552
PMCPMC13206195

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.