The DOI matches its Crossref record; 250 of the 250 references it cites were found in a registry or an index.
THE PHARMACOLOGY AND TOXICOLOGY OF CAFFEINE
Abstract
The widespread use of caffeine is most commonly linked to the stimulatory action it has on the central nervous system. Generally, adverse effects include gastrorrhea, insomnia, and diuresis. Tolerance and withdrawal symptoms have been observed and excessive consumption can lead to an anxiety neurosis condition (caffeinism). The actions of caffeine may involve its effects on neurotransmitter turnover and metabolism; its promotion of the cellular messenger, cAMP; its sensitization of the calcium releasing mechanisms of cellular reticulum; or its antagonism of the autacoid, adenosine. Caffeine lethality is rare in man but caffeine poisoning with its gastrointestinal, CNS, and cardiovascular stimulation could especially be hazardous to children. Most of the mutagenicity work has been performed in organisms whose cellular DNA synthesis and repair mechanism vary significantly from those found in man. The work in human cell lines suggests that caffeine‐induced chromosomal breakage, with its lack of chromatid exchange would promote cell lethality, not muta‐genticity. Nothing but circumstantial evidence implicates caffeine as a human carcinogen or teratogen. Involvement of caffeine as a cocarcinogen or a coteratogen (which includes effects on gamete production or fetal development) appears far more likely, but neither has even begun to be truly evaluated. Basic metabolism of caffeine involves the processes of N‐demethylation, hydration, and oxidation; and most likely requires the cytochrome P1‐450 system. Though various metabolites of caffeine are pharmacologically active, the extent of involvement of individual metabolites in the pharmacological or toxicological responses of caffeine in man is still unknown.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“However, its pain-reduction effects were not properly studied until 1984, when Lachance (96) documented that additive caffeine reduced the dose of acetaminophen necessary to achieve the target of a 40% reduction in pain scores (96).”
From The Safety of Ingested Caffeine: A Comprehensive Review (2017) · cites this paper as [96]
Citations
Cites
Items 201–250 of 250
EFFECT OF ENVIRONMENTAL TEMPERATURE ON THE TOXICITY OF CAFFEINE AND DEXTROAMPHETAMINE IN MICE
Pj, M., & Vernikos-Danellis, J. (1970) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)28456-7 · Cited by 17
BATEMAN, A. J. (1969) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(69)90121-3 · Cited by 17
Caffeine Pharmacokinetics in Young and Adult Dogs
Warszawski, D., Gorodischer, R., MOSES, S. W., & Bark, H. (2009) · Biology of the Neonate · doi:10.1159/000241007 · Cited by 17
Genetic tests in mice of caffeine alone and in combination with mutagens
Thayer, P. S., & Kensler, C. J. (1973) · Toxicology and Applied Pharmacology · doi:10.1016/s0041-008x(73)80002-x · Cited by 17
The effect of daily ingestion of caffeine on the microsomal enzymes of rat liver
Khanna, K. L., & Cornish, H. H. (1973) · Food and Cosmetics Toxicology · doi:10.1016/0015-6264(73)90057-6 · Cited by 17
Bowden, G. T., Hsu, I. C., & Harris, C. C. (1979) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(79)90067-8 · Cited by 16
Caffeine enhances skin tumor induction in MICE
Hoshino, H., & Tanooka, H. (1979) · Toxicology Letters · doi:10.1016/0378-4274(79)90078-x · Cited by 16
Meiosis suppression by caffeine in female mice
JAGIELLO, G. M., Ducayen, M. B., & Lin, J. (1972) · Molecular and General Genetics MGG · doi:10.1007/bf00333457 · Cited by 16
Metabolism of 1,3,7-trimethyldihydrouric acid in the rat: new metabolic pathway of caffeine
Arnaud, M. J. (1976) · Experientia · doi:10.1007/bf01953069 · Cited by 16
The effect of caffeine on barbiturate sleeping time and brain level.
Aeschbacher, H. U., Atkinson, J., & Domahidy, B. (1975) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)30105-9 · Cited by 15
Harrie, J. R. (1970) · JAMA · doi:10.1001/jama.1970.03170300072029 · Cited by 15
Caffeine Accumulation Associated with Alcoholic Liver Disease
(1976) · New England Journal of Medicine · doi:10.1056/nejm197607082950221 · Cited by 15
Fisher, D. L., & Gunaga, K. P. (1975) · Biology of Reproduction · doi:10.1095/biolreprod12.4.471 · Cited by 14
Effect of methylxanthines on hepatic microsomal enzymes in the rat
Aeschbacher, H., & Würzner, H.-P. (1975) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(75)90082-4 · Cited by 14
A STUDY OF THE NEUROPHARMACOLOGIC PROPERTIES OF CERTAIN CONVULSANTS, ANTICONVULSANTS AND RESERPINE
Chen, G., & Bohner, B. (1956) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)11662-5 · Cited by 13
Aldridge, A., & Neims, A. H. (1980) · Biochemical Pharmacology · doi:10.1016/0006-2952(80)90102-1 · Cited by 13
Prevention of caffeine-induced cleft palate by -glutamic acid
Zawoiski, E. J. (1976) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(76)90117-4 · Cited by 13
Effects of dietary caffeine on the testis of the domestic fowl, Gallus domesticus
AX, R. L., Collier, R. J., & Lodge, J. R. (1976) · Reproduction · doi:10.1530/jrf.0.0470235 · Cited by 12
ANTAGONISM BY CAFFEINE OF THE RESPIRATORY EFFECTS OF CODEINE AND MORPHINE
Bellville, J. W., ESCARRAGA, L. A., Wallenstein, S. L., et al. (1962) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)26257-7 · Cited by 12
Corticosteroids in Croup: Is a Controlled Clinical Trial Needed?
Eden, A. N. (1971) · PEDIATRICS · doi:10.1542/peds.47.3.635a · Cited by 11
Vogel, F., Kr�ger, J., Kurth, M., et al. (1966) · Human Genetics · doi:10.1007/bf00291514 · Cited by 11
Khanna, N. N., Harpur, E. R., & Stern, L. (1968) · Clinical Biochemistry · doi:10.1016/s0009-9120(68)80091-8 · Cited by 11
Enhancement by caffeine of the growth inhibitory effects of antimetabolites in lymphoma L5178Y cells
Lowe, J. K., & Henderson, J. F. (1977) · Biochemical Pharmacology · doi:10.1016/0006-2952(77)90429-4 · Cited by 11
ANTAGONISM BY CAFFEINE OF THE RESPIRATORY EFFECTS OF CODEINE AND MORPHINE
Bellville, J. W., ESCARRAGA, L. A., Wallenstein, S. L., et al. (1963) · Survey of Anesthesiology · doi:10.1097/00132586-196308000-00025 · Cited by 10
McColl, J. D., & Rice, W. B. (1962) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o62-059 · Cited by 10
Alternating Caffeine and Stimulants
Fras, I. A. (1974) · American Journal of Psychiatry · doi:10.1176/ajp.131.2.228-a · Cited by 10
Huidobro, F. (1945) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)08212-6 · Cited by 10
Bates, T. R., GALOWNIA, J., & Johns, W. H. (1970) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.18.656 · Cited by 9
Parathyroid Hormone Secretion in the Rat: Effect of Aminophylline
Bowser, E. N., HARGIS, G. K., HENDERSON, W. J., et al. (1975) · Experimental Biology and Medicine · doi:10.3181/00379727-148-38536 · Cited by 9
Effect of prostaglandins on the increased corticosterone output induced by caffeine in the rat
Pasquale, A. D., Costa, G., Trovato, A., et al. (1979) · Prostaglandins and Medicine · doi:10.1016/0161-4630(79)90077-6 · Cited by 9
Über den Einfluß von Coffein auf den Fett- und Kohlenhydratstoffwechsel des Menschen
Studlar, M. (1973) · Zeitschrift für Ernährungswissenschaft · doi:10.1007/bf02023909 · Cited by 9
Insomnia, Tachycardia, and Cola Drinks
Silver, W. (1971) · PEDIATRICS · doi:10.1542/peds.47.3.635 · Cited by 9
1643. Factors affecting caffeine toxicity
(1968) · Food and Cosmetics Toxicology · doi:10.1016/0015-6264(68)90339-8 · Cited by 9
[Influence of tobacco smoking on caffeine pharmacokinetics (author's transl)].
Descotes, J., Jl, B., Ollagnier, M., et al. (1980) · PubMed · Cited by 8
Coffee, Cigarettes and Peptic Ulcer
(1974) · New England Journal of Medicine · doi:10.1056/nejm197405092901924 · Cited by 8
INTERACTION OF CAFFEINE AND MORPHINE ON RESPIRATION
Bellville, J. W. (1964) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)26707-6 · Cited by 7
Adenosine 3′,5′-Monophosphate in Amniotic Fluid from Normal Pregnancy*
Ling, W. H., LeMaire, W. J., D'ADESKYC, C., et al. (1973) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-37-1-56 · Cited by 7
CAFFEINE IS NON‐MUTAGENIC TO SALMONELLA TYPHIMURIUM AND HUMAN CELLS IN CULTURE
Furth, E. E., & THILL, W. G. (1978) · Journal of Food Safety · doi:10.1111/j.1745-4565.1978.tb00276.x · Cited by 7
COMPARISON OF CAFFEINE METABOLISM BY PERFUSED RAT LIVER AND ISOLATED MICROSOMES
Arnaud, M. J., & Welsch, C. (1980) · Microsomes, Drug Oxidations and Chemical Carcinogenesis · doi:10.1016/b978-0-12-187702-6.50037-2 · Cited by 6
Rogan, E. G., Schäfer, M., Anderson, N. G., et al. (1973) · Differentiation · doi:10.1111/j.1432-0436.1973.tb00115.x · Cited by 6
Harrie, J. R. (1970) · JAMA · doi:10.1001/jama.213.4.628b · Cited by 6
INTERACTION OF CAFFEINE AND MORPHINE ON RESPIRATION
Bellville, J. W., & Hunter, A. R. (1965) · Survey of Anesthesiology · doi:10.1097/00132586-196502000-00024 · Cited by 5
A study of the effect of caffeine upon excision repair of damaged DNA
Apfelzweig, R. A., & Teplitz, R. L. (1979) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(79)90228-8 · Cited by 4
Inhibition of RNA-dependent DNA polymerase activity of oncornaviruses by caffeine
Srinivasan, A., Reddy, E. P., Sarma, P. S., et al. (1979) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(79)90609-0 · Cited by 4
THE EFFECT OF CAFFEINE ON ANTIBODY PRODUCTION
Laux, D. C. (1972) · UA Campus Repository (The University of Arizona) · Cited by 3
Reproductive toxicity of caffeine inMusca domestica
Srinivasan, A., & Kesavan, P. C. (1979) · Journal of Toxicology and Environmental Health · doi:10.1080/15287397909529786 · Cited by 3
[POTENTIATION BY THEOPHYLLINE AND CAFFEINE OF THE CONVULSANT EFFECTS AND TOXICITY OF ISONIAZID].
Besson, H., & DEBAY, A. (1964) · PubMed · Cited by 3
[THE INFLUENCING OF ADRENALINE ACTIVITY BY CAFFEINE].
Prokop, L. J. (1964) · PubMed · Cited by 3
Effects of methylxanthines on mitomycin C teratogenicity in mice
Nakatsuka, T., Hanada, T., Hanami, M., et al. (1979) · Nihon Senten Ijo Gakkai kaiho/Senten ijō · Cited by 1
Disposition of caffeine in late state pregnancy
Christensen, H. D., KLING, O. R., & Manion, C. V. (1979) · Cited by 1
Research works printed but not linked: 58
- ABOU‐ISSA H., 1982, In vitro and in vivo effects of caffeine on cyclic nucleotide metabolism in mammary tissue, Fed. Proc, 40, 665
- ALDRIDGE A., 1978, Caffeine metabolism in the developing human infant, Pharmacologist, 20, 263
- ARANDA J., 1979, Metabolism of theophylline to caffeine in human fetal liver organ cultures, Pediatr. Res, 13, 366
- ARANDA J., 1979, Effect of caffeine on control of ventilation in premature infants with apnea, Pediatr. Res, 13, 366
- ARNAUD M. J., 1980, Quantitative analysis of theophylline metabolites by hplc, after oral or iv administration, Experientia, 36, 704
- BAER H. P., 1978, Physiological and Regulatory Function of Adenosine and Adenine Nucleotides, (various authors)
- BERTRAND M., 1970, Ectrodactylie provoquee par la caffeine chez les rongeurs; role des facturs specifiques, C. R. Soc. Biol, 164, 1488
- BESSON H., 1964, Potentialisation des effets convulsivants et de la toxicite de l'isoniazide par la theophylline et la caffeine, Ann. Pharm. Fr, 22, 345
- BORLEE L, 1978, Le cafe, facteur de risque pendat la grossesse?, Louvain Med, 97, 279
- BURG A., 1977, Testimony presented before the Select Committee on GRAS Substances at a public hearing on caffeine, September 26
- CASIER M. I., 1959, Aumento della tossicita della caffeina e della sua concentrazione a livello encefalico indotto dal meprobamato, nel mus musculus indagine farmacologica e radiochimica, Arch. Int. Pharmacodyn. Ther, 122, 463
- COHEN M. H., 1975, Enhancement of the antitumor effect of 1,3‐bis(2‐chloroethy)‐1‐nitrosourea by various psychotropic drugs in combination with caffeine, J. Pharmacol. Exp. Ther, 194, 425
- COLLINS T. F. X., 1982, A comprehensive study of the teratogenic potential of caffeine in rats when given by oral intubation, J. Environ. Pathol. Toxicol
- CUZZONE H., 1982, Caffeine effects on 5‐HT uptake and release in rat cerebral cortex and midbrain raphe region, Fed. Proc, 40, 266
- DESCOTES J., 1979, Influence de la consommation de tabac sur la pharmacocinetique de la cafeine, Therapie, 34, 619
- DREISBACH R., 1943, Caffeine‐withdrawal headache, J. Lab. Clin. Med, 28, 1212
- FOLTZ E., 1942, The influence of amphetamine (benzedrine) sulfate, d‐desoxyephedrine hydrochloride (pervitin), and caffeine upon work output and recovery when rapidly exhausting work is done by trained subjects, J. Lab. Clin. Med, 28, 603
- GARCIA E., 1982, The effects of a plant fiber mix on caffeine toxicity in weanling rats, Fed. Proc, 40, 846
- GOLDMAN H. D., 1979, The kinetics of expired 14CO2 derived from the N‐demethylation of caffeine in rats as a measure of hepatic cytochrome P‐448 drug metabolism activity, Pharmacologist, 21, 206
- GOLDSTEIN A., 1965, Psychotropic effects of caffeine in man I., Individual differences in sensitivity to caffeine-induced wakefulness. J. Pharmacol. Exp. Ther, 149, 156
- GOLDSTEIN A., 1965, Psychotropic effects of caffeine in manII., Alertness, psychomotor coordination, and mood, J. Pharmacol. Exp. Ther, 150, 146
- GOLDSTEIN A., 1969, Psychotropic effects of caffeine in man, IV. Quantitative and qualitative differences associated with habituation to coffee. Clin. Pharmacol. Ther, 10, 489
- GOTH A., 1978, Medical Pharmacology, 271
- HERZ R., 1965, Caffeine inhibition of Ca uptake by muscle reticulum, Fed. Proc, 24, 208
- HIRSH K. R., 1974, Spontaneous locomotor activity changes evoked by caffeine in mice, Fed. Proc, 33, 466
- HIRSH K. R., 1974, Caffeine effects on spontaneous activity of reticular formation neurons, Neurosci. Abst, 1, 257
- HOLLINGWORTH H. L., 1912, The influence of caffeine on mental and motor efficiency, Ther. Gaz, 36, 1
- HORNING M., 1973, Fetal Pharmacology, 265
- JACOBSON M. F., 1982, Letter: Coffee and birth defects, Lancet, 1, 1415
- KAUL L., 1982, Relationship of caffeine and ethy‐nylestradiol (EE2) to hypertension in rats, Fed. Proc, 40, 930
- LSRO, (Life Science Research Office)., 1978, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, 81
- MAKLER A., 1980, Factors affecting sperm motility, IV. Incubation of human semen with caffeine, kallikrein and other metabolically active compounds. Fertil. Steril, 33, 624
- MAREN T. H., 1961, The additive renal effect of oral aminophylline and trichlormethiazide in man, Clin. Res, 9, 57
- MAU G., 1974, Kaffee‐und alkoholkonsum‐risiko‐faktoren in der schwangerschaft? Geburtsh, U. Frauenheilk, 34, 1018
- MERRILL G., 1982, Adrenergic coronary constriction and adenosine coronary dilation: the effects of respiratory hyper‐ and hypocapnia, Fed. Proc, 40, 706
- MILLER J., 1970, Carcinogenesis by chemicals: an overview, Cancer Res, 30, 559
- MITZNEGG P., 1971, The effect of ageing, caffeine-treatment, and ionizing-radiation on nucleic acid synthesis in the mouse liver life Sci, 1011, 1281
- NAGNIBEDA N., 1978, Caffeine effect on catecholamine content in perfusate of rabbit superior cervical ganglion and cat ciliar ganglion, Fiziol. Z. H, 24, 220
- NETTER K. J., 1975, Basic and Therapeutic Aspects of Perinatal Pharmacology, 39
- NICHOLS R. E., 1963, Antagonism of the vasopressor effect of ATP by caffeine, Fed. Proc, 22, 308
- PARSONS W., 1976, Stimulation of caffeine metbolism in the rat by 3‐methylcholanthrene, Fed. Proc, 35, 665
- POWERS H., 1925, The syndrome of coffee, Med. J. Rec, 121, 745
- PROKOP V. L., 1964, Die Beeinflussung der adrenalinwirkung durch koffein, Med. Klin, 59, 2016
- RITCHIE J., 1975, The Phamcological Basis of Therapeutics, 367
- ROSS V. C., 1982, Effects of acute oral caffeine treatment on spleen and thymus of male rats, Fed. Proc, 40, 738
- SKALKO R., 1982, The toxicology of chemical interactions during pregnancy in mice: caffeine and dilantin, The Toxicologist, 1, 31
- SLIZYNSKI B., 1971, Immediate effects of chemicals on mouse chromosome: I caffeine, Curr. Mod. Biol, 3, 285
- SOBOTKA T., 1979, Neurobehavioral teratology of caffeine exposure in rats, Neurotoxicology, 1, 403
- SOMMER K., 1975, Identification and quantification of drugs in human amniotic fluid, Res. Commun. Chem. Pathol. Pharmacol, 12, 583
- SPECTOR W. S., 1956, Handbook of Toxicology, 56
- U. S. BUREAU OF THE CENSUS, FOEIGN TRADE DIVISION., 1975, U. S. Imports for Consumption and General Imports. FT 246
- WALTHER H., 1962, Zur coffein und theophyllinwirkung am ermudeten rat‐tenywerchfellpraparat, Arch. Int. Pharmacodyn. Ther, 138, 597
- WARSZAWSKI D., 1980, Caffeine metabolism in liver slices of young and adult rats, Isr. J. Med. Sci, 16, 618
- WOOD H. C., 1912, The effects of caffeine on the circulatory and muscular systems, Ther. Gaz, 36, 6
- WRAGG J., 1967, Inhibition of DNA polymerase activity by caffeine in a mammalian cell line, J. Cell Biol, 35, 146A
- ZAJDELA F., 1973, Effet inhibiteur de la cafeine sur l'induction de cancers cutanes par les rayons ultraviolets chez la souris, C. R. Acad. Sci, 277, 1073
- ZAJDELA F., 1978, International Conference on Ultraviolet Carcinogenesis, National Cancer Institute Monograph 50, 130
- ZHESTYANIKOV V., 1974, The mechanisms of inhibition of the postirradiation recovery in cellsII., Inhibition of the unscheduled DNA synthesis in hela cells after UV-irradiation by caffeine and acriflavine. Tsitologiya, 16, 868
Cited by
Sorted by citations
Effects of caffeine on human health
Nawrot, P., Jordan, S., Eastwood, J., Rotstein, J., Hugenholtz, A., & Feeley, M. (2003) · Food Additives and Contaminants · doi:10.1080/0265203021000007840 · Cited by 1,199
The Safety of Ingested Caffeine: A Comprehensive Review
Temple, J. L., Bernard, C., Lipshultz, S. E., Czachor, J. D., Westphal, J. A., & Mestre, M. A. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00080 · Cited by 557
Metadata
- Authors
- LACHANCE, M. P.
- Affiliations
- University of Louisville (US)
- Corresponding author
- LACHANCE, MICHAEL P.
- Venue
- Journal of Food Safety
- Publisher
- Wiley
- Published
- 1982-06
- Volume
- 4
- Issue
- 2
- Pages
- 71-112
- ISSN
- 0149-6085 (ISSN-L)
- 1745-4565
- OpenAlex
- W2058152412
- Cited by
- 27
- References
- 250
- Citations by year
- 2022: 1 · 2021: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2012: 1
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Food Safety (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Coffee research and impacts
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Plant Toxicity and Pharmacological Properties
- Keywords
- caffeine, caffeine toxicity, caffeine pharmacology, central nervous system stimulation, caffeine withdrawal, adenosine antagonism, cyclic AMP, chromosomal damage, carcinogenesis, teratogenicity, caffeine metabolism, cytochrome P450, caffeine metabolites
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review