Diclofenac
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: Diclofenac
Examples of brand names: Voltaren [DE]
ATC code: M01AB05
Main use (for orientation): Pain; inflammation
Documented research summary
Diclofenac has substance-specific in-vitro enzyme findings and numerous experimental pharmacodynamic findings, but no clinical cannabinoid interaction confirmed from them. Static AUC models, animal gastroprotection and antibacterial cell findings are explicitly not equivalent to clinical results.
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
8 separately recorded findings. Each statement applies to its documented study context.
CBD, THC, CBN – laboratory and animal studies
Finding ID: B0380
Type of result: Preclinical / no confirmed clinical interaction
Observation: Diclofenac 4′-hydroxylation was inhibited concentration-dependently. Not time/metabolism-dependent in the experimental setup investigated.
Mechanism: Direct CYP2C9 inhibition in human liver microsomes/recombinant enzyme.
Study type: In-vitro enzyme study; abstract
Context studied: S-warfarin and diclofenac served as probes; Ki values depend on substrate/enzyme source.
Clinical interpretation: Not directly transferable to clinical dose adjustment
Limitations and uncertainties: Do not present a specific Ki from the cross-substrate abstract as a diclofenac value; no measured human AUC increase.
Original sources for this finding: Comparison in the in vitro inhibitory effects of major phytocannabinoids and polycyclic aromatic hydrocarbons contained in marijuana smoke on cytochrome P450 2C9 activity. [CA_P_22166891]
D8THC – laboratory and animal studies
Finding ID: B0381
Type of result: Preclinical / no confirmed clinical interaction
Observation: Non-competitive inhibition of diclofenac metabolism in microsomes; static models predict interaction potential.
Mechanism: Reversible CYP2C9 inhibition, also by 11-OH-D8THC.
Study type: In vitro and static model; abstract
Context studied: Recombinant and pooled human liver microsomes; carboxylated metabolite without relevant inhibition.
Clinical interpretation: Not directly transferable to clinical dose adjustment
Limitations and uncertainties: Not a clinical study; abstract alone does not justify classification as an established strong human interaction.
Original sources for this finding: Inhibitory effects of Δ8-tetrahydrocannabinol on major hepatic cytochrome P450 enzymes and implications for drug disposition. [CA_P_40829519]
CBD, THC – laboratory and animal studies
Finding ID: B0382
Type of result: Preclinical / no confirmed clinical interaction
Observation: Maximum predicted diclofenac AUC ratios: oral CBD 700 mg, 9.6; oral THC 130 mg, 6.6, or inhaled 75 mg, 2.3.
Mechanism: Static CYP inhibition modelling.
Study type: In-vitro-based static models; abstract
Context studied: Figures are model maxima under different assumptions, not measurements in treated patients.
Clinical interpretation: Not directly transferable to clinical dose adjustment
Limitations and uncertainties: Do not use as an actual exposure increase or dosage rule; clinical validation absent.
Original sources for this finding: Comprehensive Predictions of Cytochrome P450 (P450)-Mediated In Vivo Cannabinoid-Drug Interactions Based on Reversible and Time-Dependent P450 Inhibition in Human Liver Microsomes. [BMED35115300]
CBD – laboratory and animal studies
Finding ID: B0383
Type of result: Preclinical / no confirmed clinical interaction
Observation: Synergy for ATCC S. epidermidis (FICI 0.258), additive effect for ATCC S. aureus; four clinical isolates showed only indifferent/additive interactions. No effect against tested Gram-negative bacteria.
Mechanism: Experimental antibacterial pharmacodynamics.
Study type: In-vitro bacterial strains and fibroblasts
Context studied: Checkerboard: combination, for example, 3.906 µg/ml of each component; time-kill used CBD 3.906 and diclofenac 500 µg/ml.
Clinical interpretation: Not directly transferable to clinical dose adjustment
Limitations and uncertainties: Do not equate the different diclofenac doses. Mechanism hypothetical only; not human efficacy/safety evidence. Abstract is broader than the clinical-isolate findings.
Original sources for this finding: Combining Diclofenac and Cannabidiol to Enhance the Antibacterial Capacity of Nonantibiotic Drugs Through Potentiation. [C_PR_42450264]
CBD (CBD-rich extract) – laboratory and animal studies
Finding ID: B0384
Type of result: Preclinical / no confirmed clinical interaction
Observation: CBD plus diclofenac suppressed the acetylcholine response more than CBD alone: approximately 5.1% versus 26.5% of baseline contraction.
Mechanism: Ex-vivo inhibition of intestinal contractility.
Study type: Ex-vivo rat intestine, n=5 replicates
Context studied: Diclofenac 100 µM; CBD 25 µg/ml (~80 µM), extract containing CBD 887.17 mg/g with small amounts of other phytocannabinoids.
Clinical interpretation: Not directly transferable to clinical dose adjustment
Limitations and uncertainties: High organ-bath concentrations; not proven clinical constipation. Endocannabinoid synthesis as an explanation not directly measured.
Original sources for this finding: Diclofenac and dexamethasone modulate the effect of cannabidiol on the rat colon motility ex vivo. [C_PR_38143819]
CBD + CBG + THCV (mixture) – laboratory and animal studies
Finding ID: B0385
Type of result: Preclinical / no confirmed clinical interaction
Observation: FCBD:std and diclofenac synergistically reduced IL-8; co-culture/3D additionally showed reduced inflammatory markers at selected concentrations.
Mechanism: Inflammatory markers/Bliss synergy in cell models.
Study type: In-vitro 2D/3D models
Context studied: KG1/A549, for example FCBD:std 30 µg/ml and diclofenac 50–100 µg/ml in macrophages.
Clinical interpretation: Not directly transferable to clinical dose adjustment
Limitations and uncertainties: Do not attribute to individual cannabinoids; not clinical anti-inflammatory synergy or safety.
Original sources for this finding: Phytocannabinoids Act Synergistically with Non-Steroidal Anti-Inflammatory Drugs Reducing Inflammation in 2D and 3D In Vitro Models. [C_PR_36559009]
THC – laboratory and animal studies
Finding ID: B0386
Type of result: Preclinical / no confirmed clinical interaction
Observation: THC reduced diclofenac-induced gastric haemorrhagic streaks in fasted mice; ED50 0.64 mg/kg orally or 0.06 mg/kg intraperitoneally.
Mechanism: Experimental protection against NSAID gastropathy.
Study type: Mouse experiment; abstract
Context studied: Oral diclofenac 100 mg/kg; THC before diclofenac.
Clinical interpretation: Not directly transferable to clinical dose adjustment
Limitations and uncertainties: No clinical gastroprotection established; does not replace established ulcer prophylaxis. Full text inaccessible.
Original sources for this finding: Acute Δ(9)-tetrahydrocannabinol blocks gastric hemorrhages induced by the nonsteroidal anti-inflammatory drug diclofenac sodium in mice. [C_PR_23769745]
D8THC – laboratory and animal studies
Finding ID: B0387
Type of result: Preclinical / no confirmed clinical interaction
Observation: Diclofenac attenuated D8THC-induced suppression of lever pressing in rats.
Mechanism: Arachidonic-acid/COX/prostanoid EP3-mediated behavioural pharmacodynamics.
Study type: Rat behavioural studies; abstracts
Context studied: 2001: among other substances, diclofenac 32 mg/kg intraperitoneally; mechanistic follow-up in 2004.
Clinical interpretation: Not directly transferable to clinical dose adjustment
Limitations and uncertainties: No evidence that diclofenac reverses human cannabis intoxication; do not count studies as clinical replications.
Original sources for this finding: Behavioral suppression induced by cannabinoids is due to activation of the arachidonic acid cascade in rats. [BMED11166698]; Activation of brain prostanoid EP3 receptors via arachidonic acid cascade during behavioral suppression induced by Delta8-tetrahydrocannabinol. [C_PR_14675158]
References and access status
[C_LABEL_D0164] DICLOFENAC SODIUM DELAYED RELEASE (DICLOFENAC SODIUM) TABLET, DELAYED RELEASE [PREFERRED PHARMACEUTICALS INC.]
Original source / bibliographic reference
Authors: PREFERRED PHARMACEUTICALS 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_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)
[BMED11166698] Behavioral suppression induced by cannabinoids is due to activation of the arachidonic acid cascade in rats.
Original source / bibliographic reference
Authors: Yamaguchi T, Shoyama Y, Watanabe S, Yamamoto T.
Year: 2001
Source type: Publication; title and abstract reviewed
DOI: 10.1016/s0006-8993(00)03127-9
PMID: 11166698
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)
[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_14675158] Activation of brain prostanoid EP3 receptors via arachidonic acid cascade during behavioral suppression induced by Delta8-tetrahydrocannabinol.
Original source / bibliographic reference
Authors: Yamaguchi T, Kubota T, Watanabe S, Yamamoto T.
Year: 2004
Source type: Primary source, abstract read
DOI: 10.1046/j.1471-4159.2003.02151.x
PMID: 14675158
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_22166891] Comparison in the in vitro inhibitory effects of major phytocannabinoids and polycyclic aromatic hydrocarbons contained in marijuana smoke on cytochrome P450 2C9 activity.
Original source / bibliographic reference
Authors: Yamaori S, Koeda K, Kushihara M, Hada Y, Yamamoto I, Watanabe K.
Year: 2012
Source type: Comparative Study; Research Support, Non-U.S. Gov't; Journal Article
DOI: 10.2133/dmpk.dmpk-11-rg-107
PMID: 22166891
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_23769745] Acute Δ(9)-tetrahydrocannabinol blocks gastric hemorrhages induced by the nonsteroidal anti-inflammatory drug diclofenac sodium in mice.
Original source / bibliographic reference
Authors: Kinsey SG, Cole EC.
Year: 2013
Source type: Primary source, abstract read
DOI: 10.1016/j.ejphar.2013.06.001
PMID: 23769745
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)
[BMED35115300] Comprehensive Predictions of Cytochrome P450 (P450)-Mediated In Vivo Cannabinoid-Drug Interactions Based on Reversible and Time-Dependent P450 Inhibition in Human Liver Microsomes.
Original source / bibliographic reference
Authors: Bansal S, Paine MF, Unadkat JD.
Year: 2022
Source type: Primary publication; abstract reviewed
DOI: 10.1124/dmd.121.000734
PMID: 35115300
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_36557911] Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell Carcinoma.
Original source / bibliographic reference
Authors: Krajka-Kuźniak V, Papierska K, Narożna M, Jelińska A, Majchrzak-Celińska A.
Year: 2022
Source type: Primary source, relevant full-text sections read
DOI: 10.3390/molecules27248779
PMID: 36557911
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_36559009] Phytocannabinoids Act Synergistically with Non-Steroidal Anti-Inflammatory Drugs Reducing Inflammation in 2D and 3D In Vitro Models.
Original source / bibliographic reference
Authors: Vinayaka AC, Shalev N, Anil SM, Tiwari S, Kumar N, Belausov E, Mani KA, Mechrez G, Koltai H.
Year: 2022
Source type: Primary source, relevant full-text sections read
DOI: 10.3390/ph15121559
PMID: 36559009
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_38143819] Diclofenac and dexamethasone modulate the effect of cannabidiol on the rat colon motility ex vivo.
Original source / bibliographic reference
Authors: Chłopecka M, Kiraga Ł, Crowley K, Jank M, Latek U, Mendel M, Karlik W.
Year: 2023
Source type: Primary source, relevant full-text sections read
DOI: 10.2478/jvetres-2023-0029
PMID: 38143819
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)
[CA_P_40829519] Inhibitory effects of Δ8-tetrahydrocannabinol on major hepatic cytochrome P450 enzymes and implications for drug disposition.
Original source / bibliographic reference
Authors: Zhao M, Coates S, Bardhi K, Lazarus P.
Year: 2025
Source type: research-article; Journal Article
DOI: 10.1016/j.dmd.2025.100122
PMID: 40829519
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.
[C_PR_42450264] Combining Diclofenac and Cannabidiol to Enhance the Antibacterial Capacity of Nonantibiotic Drugs Through Potentiation.
Original source / bibliographic reference
Authors: Gradisteanu Pircalabioru G, Tihauan BM, Iliescu C, Iliescu FS.
Year: 2026
Source type: Primary source, relevant full-text sections read
DOI: 10.3390/ijms27135997
PMID: 42450264
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_42771648] Evaluating the impact of cannabinoid extracts on chronic pain and quality of life in endometriosis patients - a pilot study.
Original source / bibliographic reference
Authors: Kratz JW, Velho RV, Bock S, Sehouli J, Mechsner S.
Year: 2026
Source type: Primary source, relevant full-text sections read
DOI: 10.1371/journal.pone.0356768
PMID: 42771648
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)
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
Diclofenac and cannabinoids: documented findings, evidence, sources and data gaps. Research information for discussion with your doctor or pharmacist.