Paracetamol

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: Paracetamol

Examples of brand names: Ben-u-ron [DE]

ATC code: N02BE01

Main use (for orientation): Pain; fever

Documented research summary

Direct human exposure with CBD has been investigated: no additional benefit in knee osteoarthritis and a liver-test signal, but without a CBD-only arm this does not prove a specific synergy. Extract/mouse toxicity and a weak single case are recorded separately. No assurance of safety for untested cannabinoids.

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 – clinically studied

Finding ID: B0368

Type of result: Clinical evidence

Observation: No additional analgesic benefit in the knee-osteoarthritis RCT; more liver-test elevations with CBD plus paracetamol than placebo plus paracetamol.

Mechanism: CBD as adjunctive therapy; liver-test signal, mechanism not isolated.

Study type: Randomised double-blind placebo-controlled study

Context studied: 86 randomised, 84 treated, 58 completed; CBD 600 mg/day for 8 weeks with intended additional paracetamol 3 g/day. WOMAC change 2.5 versus 2.4; p=0.80. Any liver-test elevation 15 versus 5; p=0.02.

Clinical interpretation: Direct combination exposure, but not an isolated pharmacokinetic interaction

Limitations and uncertainties: Relevant AST/ALT elevations individually NOT significant (2 versus 0, p=0.494 / 3 versus 0, p=0.24); γGT 11 versus 0 significant. No serious adverse events; elevations reversible at follow-up. No CBD-only arm or pharmacokinetics, therefore no proven hepatotoxic synergy; 28% reduced paracetamol.

Original sources for this finding: Oral cannabidiol (CBD) as add-on to paracetamol for painful chronic osteoarthritis of the knee: a randomized, double-blind, placebo-controlled clinical trial. [C_PR_38033459]

CBD-rich extract – laboratory and animal studies

Finding ID: B0369

Type of result: Preclinical evidence

Observation: Lower extract dose enhanced liver injury and mortality, higher dose did not; non-monotonic dose response.

Mechanism: Oxidative stress, impaired new glutathione synthesis/JNK; no increased paracetamol-protein adducts between paracetamol groups.

Study type: Mouse experiment

Context studied: Nine-month-old female CD1 mice, CBD 116 or 290 mg/kg orally in extract for 3 days, then paracetamol 400 mg/kg intraperitoneally; 3/8 deaths with 116 mg/kg plus paracetamol, none with the higher combination/paracetamol alone. Extract: 57.9% CBD, 2.03% CBC, 1.69% THC, 1.07% CBG.

Clinical interpretation: Not quantitatively transferable to humans

Limitations and uncertainties: Not pure CBD; high doses/different route/specific population; authors' allometry is not clinical dose evidence.

Original sources for this finding: Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration. [C_PR_31212965]

Cannabis oil (described as CBD) – clinical signals

Finding ID: B0370

Type of result: Very weak clinical signal

Observation: ALT >6000 IU/l after cannabis oil plus sporadic paracetamol and recent flucloxacillin; improvement after discontinuation. Causal contributions cannot be resolved.

Mechanism: Suspected multifactorial hepatotoxic reaction; not demonstrated CYP synergy.

Study type: Single case report

Context studied: 45-year-old woman, oil 1 ml 3–4 times/day for 14 days; cannabinoid concentration unknown; flucloxacillin 2 weeks earlier, paracetamol dose unclear, 1–1.5 g at presentation.

Clinical interpretation: Signal, not a proven pair interaction

Limitations and uncertainties: The R factor describes injury pattern, not a causality score; the article uses it incorrectly. A low single paracetamol concentration does not exclude preceding toxicity; delayed flucloxacillin-induced liver injury not excluded. No rechallenge/exposure analysis. Speculative CYP explanations not adopted.

Original sources for this finding: Unveiling the Unexpected: A Case of Synergistic Drug Reaction to Cannabidiol. [C_PR_41018322]

Cannabis resin – laboratory and animal studies

Finding ID: B0371

Type of result: Preclinical evidence

Observation: Paracetamol antagonised the cannabis-resin-induced increase in brain serotonin concentration in a rat experiment.

Mechanism: Pharmacodynamic/prostaglandin–serotonin modulation.

Study type: Animal experiment; abstract

Context studied: 1983 resin extract, not defined exposure to an individual cannabinoid.

Clinical interpretation: Human relevance not demonstrated

Limitations and uncertainties: Not transferable to pure THC/CBD/the other cannabinoids in the 28-cannabinoid set; full text not read.

Original sources for this finding: Prostaglandin synthesis inhibitors reduce Cannabis and restraint stress induced increase in rat brain serotonin concentrations. [C_PR_6683450]

References and access status

[C_LABEL_D0161_UK] Paracetamol 500 mg Tablet, Medley Pharma UK SmPC

Original source / bibliographic reference

Authors: Medley Pharma Limited

Year: 2025

Source type: Official UK SmPC

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

Bibliographic attribution or source identity cross-checked.

[C_PR_41018322] Unveiling the Unexpected: A Case of Synergistic Drug Reaction to Cannabidiol.

Original source / bibliographic reference

Authors: Balouch A, Balouch A, Muslim MO, Akram M, Haseeb SS, Chaudhary MN.

Year: 2025

Source type: Primary source, full text read

DOI: 10.7759/cureus.90992

PMID: 41018322

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

PubMed Central – archived text

DOI – publisher access (access restrictions may apply)

[C_PR_38033459] Oral cannabidiol (CBD) as add-on to paracetamol for painful chronic osteoarthritis of the knee: a randomized, double-blind, placebo-controlled clinical trial.

Original source / bibliographic reference

Authors: Pramhas S, Thalhammer T, Terner S, Pickelsberger D, Gleiss A, Sator S, Kress HG.

Year: 2023

Source type: Primary source, full text read

DOI: 10.1016/j.lanepe.2023.100777

PMID: 38033459

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

PubMed Central – archived text

DOI – publisher access (access restrictions may apply)

[C_PR_31212965] Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration.

Original source / bibliographic reference

Authors: Ewing LE, McGill MR, Yee EU, Quick CM, Skinner CM, Kennon-McGill S, Clemens M, Vazquez JH, McCullough SS, Williams DK, Kutanzi KR, Walker LA, ElSohly MA, James LP, Gurley BJ, Koturbash I.

Year: 2019

Source type: Primary source, full text read

DOI: 10.3390/molecules24122256

PMID: 31212965

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

PubMed Central – archived text

DOI – publisher access (access restrictions may apply)

[C_PR_6683450] Prostaglandin synthesis inhibitors reduce Cannabis and restraint stress induced increase in rat brain serotonin concentrations.

Original source / bibliographic reference

Authors: Bhattacharya SK, Bhattacharya D.

Year: 1983

Source type: Primary source, abstract read

DOI: 10.1515/znc-1983-3-430

PMID: 6683450

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)

[BMED12235269] Decrease in efficacy and potency of nonsteroidal anti-inflammatory drugs by chronic delta(9)-tetrahydrocannabinol administration.

Original source / bibliographic reference

Authors: Anikwue R, Huffman JW, Martin ZL, Welch SP.

Year: 2002

Source type: Publication; title and abstract reviewed

DOI: 10.1124/jpet.303.1.340

PMID: 12235269

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)

[C_PR_1666916] Tissue glutathione levels in mice treated with delta-9-tetrahydrocannabinol.

Original source / bibliographic reference

Authors: Husain S, Ahmed KM.

Year: 1991

Source type: Primary source, abstract read

DOI: 10.1016/0091-3057(91)90356-7

PMID: 1666916

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