Caffeine
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: Caffeine
Examples of brand names: Coffeinum N [DE]; Peyona [EU]
ATC code: N06BC01
Main use (for orientation): Fatigue; apnoea of prematurity depending on formulation
Documented research summary
CBD can clinically increase caffeine exposure at high pharmaceutical doses. Newer human pharmacodynamic combination data show dose/product-dependent effects; no individual human pair evidence for rare cannabinoids. Preclinical memory effects and a coronary-spasm case justify neither blanket causal claims nor safety claims.
Uncertainties and limitations
Peyona is neonatal oral/intravenous citrate; do not directly extrapolate adult CBD studies and caffeine-base doses to premature infants.
Shared enzymes must not be equated with clinical evidence of an interaction; CBD/THC findings cannot be extrapolated to other cannabinoids.
Separately recorded findings
8 separately recorded findings. Each statement applies to its documented study context.
CBD – clinically studied
Finding ID: B0018
Type of result: Positive finding / indication
Observation: AUC0–∞ +95%, AUC0–t +88%; Cmax +15%; mean half-life 5.4→10.9 hours (not statistically tested).
Mechanism: CYP1A2 inhibition
Study type: Open-label phase I pharmacokinetics
Context studied: CBD 750 mg twice daily; caffeine 200 mg; 9/16 completed.
Clinical interpretation: Possible, exposure-dependent
Limitations and uncertainties: High CBD range; substantial attrition.
Original sources for this finding: A Phase 1 Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Trial to Investigate the Effect of Cannabidiol on the CYP1A2 Probe Caffeine in Healthy Subjects [CL06]
CBD + Δ9-THC (oral extract) – clinically studied
Finding ID: B0024
Type of result: Positive finding / indication
Observation: AUC +39%.
Mechanism: CYP1A2 probe
Study type: Randomised crossover pharmacokinetic study
Context studied: n=18; caffeine 100 mg within a shared CYP probe cocktail 30 minutes after CBD-rich plant extract (640 mg CBD plus 20 mg THC) in a brownie versus placebo. Double-blind randomised crossover; at least one-week washout; standardised low-fat breakfast one hour before the brownie; sampling 0–24 hours.
Clinical interpretation: Pharmacokinetic signal; clinical consequences undetermined
Limitations and uncertainties: Not a CBD-only study.
Original sources for this finding: Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants [CL09]
Δ9-THC (oral extract without CBD) – clinically studied
Finding ID: B0029
Type of result: No / minor effect under the conditions studied
Observation: No inhibition signal.
Mechanism: CYP probe
Study type: Randomised crossover pharmacokinetic study
Context studied: n=18; caffeine 100 mg within a shared CYP probe cocktail 30 minutes after THC plant extract (20 mg THC, no CBD) in a brownie versus placebo. Double-blind randomised crossover; at least one-week washout; standardised low-fat breakfast one hour before the brownie; sampling 0–24 hours.
Clinical interpretation: Null finding
Limitations and uncertainties: Single administration; no general assurance of safety.
Original sources for this finding: Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants [CL09]
Δ9-THC with/without CBD – clinically investigated
Finding ID: B0232
Type of result: Clinical evidence
Observation: Caffeine alone changed THC effects/metabolism only slightly; CBD in the triple combination increased THC/11-OH-THC and subjective/performance impairment.
Mechanism: Human pharmacokinetics/pharmacodynamics
Study type: Randomised double-blind crossover study
Context studied: n=20; cumulative oral THC 7.5 mg, caffeine 180 mg, CBD 105 mg.
Clinical interpretation: Context-specific finding, not a recommendation for use
Limitations and uncertainties: No general assurance of safety; the CBD triple combination is not an isolated caffeine–CBD pair effect.
Original sources for this finding: Effect of caffeine and cannabidiol (CBD) co-administration on Δ9-tetrahydrocannabinol (Δ9-THC) subjective effects, performance impairment, and pharmacokinetics. [BMED40962814]
CBD – clinically studied
Finding ID: B0233
Type of result: Clinical evidence – limited
Observation: A preliminary online experiment found few changes in subjective effects and no newly apparent negative effects.
Mechanism: Subjective acute effect
Study type: Randomised exploratory study
Context studied: n=54; caffeine 200 mg plus CBD 25–240 mg; self-report over 140 minutes.
Clinical interpretation: Context-specific finding, not a recommendation for use
Limitations and uncertainties: No pharmacokinetics, small groups, no long-term safety or equivalence established.
Original sources for this finding: A preliminary investigation of the simultaneous effects of cannabidiol and caffeine. [BMED37917507]
Cannabis/cannabinoids not quantified – clinical signals
Finding ID: B0234
Type of result: Clinical observation – not causal
Observation: A high-risk patient had recurrent coronary spasms/cardiac arrests with cannabis use and high cola consumption.
Mechanism: Coronary spasm
Study type: Single case
Context studied: Aged 47, chronic coronary syndrome; at least 3 litres of cola daily; cannabinoid content unclear.
Clinical interpretation: Context-specific finding, not a recommendation for use
Limitations and uncertainties: No isolated pair causality; comorbidity and exposure uncertainty.
Original sources for this finding: When coronary spasm strikes: a case report on the dreadful association between cannabinoids and caffeine. [BMED40458770]
THC – laboratory and animal studies
Finding ID: B0235
Type of result: Preclinical evidence
Observation: Caffeine enhanced THC memory deficits in selected rat/mouse models; an older rabbit model showed different EEG/behavioural antagonism.
Mechanism: Adenosine/CB1-dependent memory effects
Study type: Animal/synapse models
Context studied: Different doses, chronic versus acute exposure and endpoints.
Clinical interpretation: Context-specific finding, not a recommendation for use
Limitations and uncertainties: Not a clinical antidote or universal potentiation prediction.
Original sources for this finding: Combined effects of THC and caffeine on working memory in rats. [BMED21699509]; Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration: implications for the effects of Δ9-tetrahydrocannabinol on spatial memory. [BMED20927050]; Control of cannabinoid CB1 receptor function on glutamate axon terminals by endogenous adenosine acting at A1 receptors. [BMED20071517]; EEG and behavioral effects of delta9-tetrahydrocannabinol in combination with stimulant drugs in rabbits. [BMED827761]
CBD – laboratory and animal studies
Finding ID: B0236
Type of result: Preclinical evidence
Observation: Caffeine pretreatment prevented a CBD-related memory change in zebrafish; CBD/theanine improved caffeine-disrupted sleep in a mouse model.
Mechanism: Memory/sleep models
Study type: Zebrafish/mouse
Context studied: High-dose/multiple-combination models; theanine and pentobarbital in the sleep experiment.
Clinical interpretation: Context-specific finding, not a recommendation for use
Limitations and uncertainties: Does not support use in humans.
Original sources for this finding: Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio). [BMED26099242]; Combined Administration of Cannabidiol and L-Theanine Improves Sleep-Related Outcomes in Caffeine-Induced Sleep Disturbances Mouse Model. [BMED42375087]
References and access status
[BWEB11] Peyona 20 mg/ml solution for infusion and oral solution – SmPC
Original source / bibliographic reference
Authors: Chiesi Limited
Year: 2024
Source type: Official prescribing information (UK)
Source access – 23 October 2026: Source destination was accessible when checked.
Bibliographic attribution or source identity cross-checked.
[CL06] A Phase 1 Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Trial to Investigate the Effect of Cannabidiol on the CYP1A2 Probe Caffeine in Healthy Subjects
Original source / bibliographic reference
Authors: Thai C; Tayo B; Critchley D
Year: 2021
Source type: Open-label phase I study, fixed sequence
DOI: 10.1002/cpdd.950
PMID: 33951339
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.
[CL09] Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants
Original source / bibliographic reference
Authors: Bansal S; Zamarripa CA; Spindle TR; Weerts EM; Thummel KE; Vandrey RG; Paine MF; Unadkat JD
Year: 2023
Source type: Randomised placebo-controlled crossover probe study
DOI: 10.1002/cpt.2973
PMID: 37313955
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.
[BMED40962814] Effect of caffeine and cannabidiol (CBD) co-administration on Δ9-tetrahydrocannabinol (Δ9-THC) subjective effects, performance impairment, and pharmacokinetics.
Original source / bibliographic reference
Authors: Strickland JC, Tilton HE, Patton NM, Vandrey R, Austin Zamarripa C, Spindle TR, Lee DC, Bergeria CL, Wolinsky D, Klawitter J, Sempio C, Campos-Palomino J, Christians U, Feldner MT, Irons JG, Bonn-Miller MO.
Year: 2025
Source type: Publication; title and abstract reviewed
DOI: 10.1038/s41386-025-02232-x
PMID: 40962814
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)
[BMED42375087] Combined Administration of Cannabidiol and L-Theanine Improves Sleep-Related Outcomes in Caffeine-Induced Sleep Disturbances Mouse Model.
Original source / bibliographic reference
Authors: Kim J, Yu YJ, Kim HK, Ullah A, Bappi MH, Shim HJ, Cheong J, Compomayor NB, Kim HJ, Chae HJ.
Year: 2026
Source type: Publication; title and abstract reviewed
DOI: 10.4062/biomolther.2025.160
PMID: 42375087
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)
[BMED37917507] A preliminary investigation of the simultaneous effects of cannabidiol and caffeine.
Original source / bibliographic reference
Authors: Ferretti ML, Gustin ND, Sokol CM, Zamarripa CA, Feldner MT, Bonn-Miller MO, Irons JG.
Year: 2024
Source type: Publication; title and abstract reviewed
DOI: 10.1037/pha0000691
PMID: 37917507
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)
[BMED40458770] When coronary spasm strikes: a case report on the dreadful association between cannabinoids and caffeine.
Original source / bibliographic reference
Authors: Colombo G, Selimi A, Cesari A, Pedrotti P, Sacco A.
Year: 2025
Source type: Publication; title and abstract reviewed
DOI: 10.1093/ehjcr/ytaf252
PMID: 40458770
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)
[BMED32415526] Cannabidiol Prevents the Expression of the Locomotor Sensitization and the Metabolic Changes in the Nucleus Accumbens and Prefrontal Cortex Elicited by the Combined Administration of Cocaine and Caffeine in Rats.
Original source / bibliographic reference
Authors: Prieto JP, López Hill X, Urbanavicius J, Sanchez V, Nadal X, Scorza C.
Year: 2020
Source type: Publication; title and abstract reviewed
DOI: 10.1007/s12640-020-00218-9
PMID: 32415526
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)
[BMED26099242] Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio).
Original source / bibliographic reference
Authors: Nazario LR, Antonioli R, Capiotti KM, Hallak JE, Zuardi AW, Crippa JA, Bonan CD, da Silva RS.
Year: 2015
Source type: Publication; title and abstract reviewed
DOI: 10.1016/j.pbb.2015.06.008
PMID: 26099242
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)
[BMED21699509] Combined effects of THC and caffeine on working memory in rats.
Original source / bibliographic reference
Authors: Panlilio LV, Ferré S, Yasar S, Thorndike EB, Schindler CW, Goldberg SR.
Year: 2012
Source type: Publication; title and abstract reviewed
DOI: 10.1111/j.1476-5381.2011.01554.x
PMID: 21699509
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)
[BMED20927050] Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration: implications for the effects of Δ9-tetrahydrocannabinol on spatial memory.
Original source / bibliographic reference
Authors: Sousa VC, Assaife-Lopes N, Ribeiro JA, Pratt JA, Brett RR, Sebastião AM.
Year: 2011
Source type: Publication; title and abstract reviewed
DOI: 10.1038/npp.2010.179
PMID: 20927050
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)
[BMED28588361] Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats.
Original source / bibliographic reference
Authors: Owolabi JO, Olatunji SY, Olanrewaju AJ.
Year: 2017
Source type: Publication; title and abstract reviewed
DOI: 10.1159/000475895
PMID: 28588361
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)
[BMED20071517] Control of cannabinoid CB1 receptor function on glutamate axon terminals by endogenous adenosine acting at A1 receptors.
Original source / bibliographic reference
Authors: Hoffman AF, Laaris N, Kawamura M, Masino SA, Lupica CR.
Year: 2010
Source type: Publication; title and abstract reviewed
DOI: 10.1523/jneurosci.4920-09.2010
PMID: 20071517
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)
[BMED827761] EEG and behavioral effects of delta9-tetrahydrocannabinol in combination with stimulant drugs in rabbits.
Original source / bibliographic reference
Authors: Consroe P, Jones B, Laird H.
Year: 1976
Source type: Publication; title and abstract reviewed
DOI: 10.1007/bf00634153
PMID: 827761
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)
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
Caffeine and cannabinoids: documented findings, evidence, sources and data gaps. Research information for discussion with your doctor or pharmacist.