Skip to main content

Kola Nut

Scientific Name(s): Cola acuminata, Cola nitidi
Common Name(s): Abata cola, Bissy nut, Cola, Cola nut, Guru nut

Medically reviewed by Last updated on Sep 1, 2022.

Clinical Overview


Kola nuts are commonly chewed in West and Northern Africa for their stimulant properties and to aid digestion and suppress cough. A formulation of kola nuts and coca leaves as a remedy for headache led to the commercial carbonated cola drink, Coca-Cola, in the 1880s. Kola nut extract is used in the food industry as a flavoring ingredient. Clinical trials are lacking to support use; however, CNS stimulation is evident, likely due to the caffeine content.


Clinical studies are lacking to provide dosing guidance.


Contraindications have not been identified.


Kola nut has US Food and Drug Administration (FDA) generally recognized as safe (GRAS) status; however, information regarding safety and efficacy in pregnancy and lactation is lacking.


See Drug Interactions section.

Adverse Reactions

Case reports and clinical studies are lacking to identify potential adverse reactions.


Kola nut has FDA GRAS status and is used in the food industry. The high amine content may be related to oral and GI cancers observed among habitual chewers of kola nut.

Scientific Family

  • Malvaceae (mallow)
  • Sterculiaceae (Cocoa)


C. acuminata is a moderately large evergreen tree (20 m) that produces green-white flowers with a central, purple-colored striation. The star-shaped fruits contain follicles that hold the bean-like seeds, the cotyledon of which is the sweet-smelling, bitter, brown kola nut. After drying, the nut is milder and aromatic.(Maurice 2014, USDA 2022)

C. acuminata, should not be confused with Garcinia kola (Clusiacae family).(Ojo 2021)


A formulation of coca leaves and kola nuts was invented by an American pharmacist in the 1880s, initially as a headache and hangover remedy, then later as the first carbonated commercial Coca-Cola drink. The cola drink recipe no longer contains kola nut extract; however, kola nut extract continues to be used in the food industry as a flavoring ingredient.(Burdock 2009)

The nuts are commonly chewed in West and Northern Africa for their stimulant properties, with purported effects including increased energy and strength and the ability to stave off hunger and drowsiness. The seed also reportedly aids digestion and suppresses cough.(Atawodi 1995, Skarupova 2020)

In Uganda, C. acuminata (known as ngongolia) is reportedly used for erectile dysfunction,(Kamatenesi-Mugisha 2005) although reports of use may be due to misidentification of the unrelated G. kola.(Ojo 2021)


Chemical compounds in the leaves and plant parts of C. acuminata have been identified and include tannoids (catechol and epicatechol), caffeine (1,3,7-trimethylxanthine; up to 3% of dry weight), theobromine, and theophylline.(Adeyeye 1994, Ekalu 2020, Skarupova 2020) Flavonoids, anthocyanins, and tannins have been described.(Burdock 2009) The amine content has also been studied.(Atawodi 1995) The presence of cardiac glycosides has also been suggested.(Ekalu 2020) Polyphenols and other compounds with biological activity are present in higher quantities in the seeds than the leaves.(Dah Nouvlessounon 2015)

The composition of fresh kola nuts differs from that of processed or dried nuts, and heat treatment may deactivate certain enzymes involved in the release of caffeine.(Adeyeye 1994, Burdock 2009)

Uses and Pharmacology

CNS effects

Animal and in vitro data

Limited animal and in vitro studies suggest kola nut extract and caffeine exert similar neurological effects.(Burdock 2009) Anticholinesterase activity of aqueous C. acuminata seed extract has also been demonstrated in vitro, leading to claims regarding potential protective effects against neurodegenerative disease.(Oboh 2014)

Clinical data

Clinical studies are lacking. The CNS stimulant effects of 1 nut have been reported to be equal to or greater than effects of the caffeine content of 2 large cups of coffee.(Burdock 2009)

Erectile dysfunction

In a study documenting medicinal plants used in the treatment of sexual impotence and erectile dysfunction disorders in Uganda, C. acuminata was identified as a plant used for erectile dysfunction,(Kamatenesi-Mugisha 2005) although reports of use may be due to misidentification of the unrelated G. kola, which contains garcinoic acid and exhibits an affinity for the phosphodiesterase type 5 receptor.(Ojo 2021)

Hypoglycemic effects

Animal and ethnobotanical data

Limited studies in rats and ethnobotanical investigations suggest C. acuminata may possess hypoglycemic effects.(Ekalu 2020)

Ultraviolet A protection

Animal data

In a study evaluating the ultraviolet A (UVA) protective potential of plant extracts and phytochemicals, the methylxanthine content of C. acuminata was suggested to be responsible for observed effects in reducing harm from UVA radiation in mice.(Skarupova 2020)


Clinical studies are lacking to provide dosing guidance. The CNS stimulant effects of 1 nut have been reported to be equal to or greater than effects of the caffeine content of 2 large cups of coffee.(Burdock 2009)

Pregnancy / Lactation

Kola nut has FDA GRAS status.(FDA 2021b) A study in pregnant mice using high-dose kola nut reported a significant decrease in pup body weights.(Burdock 2009)


Potential for kola nut to interact with various drugs has been theorized, including with ephedrine, monoamine oxidase inhibitors, adenosine, clozapine, benzodiazepines, beta-blockers, phenylpropanolamine, and quinolone antibiotics; however, case reports are lacking.(Burdock 2009)

CNS stimulants/Acebrophylline: Acebrophylline may enhance the stimulatory effect of CNS stimulants. Avoid combination.(Acebrophylline 2014)

Doxofylline/Caffeine and caffeine-containing products: Caffeine and caffeine-containing products may enhance the adverse/toxic effect of doxofylline. Avoid combination.(Doxofylline 2015)

Iobenguane radiopharmaceutical products/CNS stimulants: CNS stimulants may diminish the therapeutic effect of iobenguane radiopharmaceutical products. Avoid combination.(Adaniya 2021, AdreView March 2020, Azedra July 2018, Estorch 2004, Muraoka 2008, Nakajo 1984, Yokoyama 2014)

Sympathomimetics/Kratom: Kratom may enhance the adverse/toxic effect of sympathomimetics. Avoid combination.(Boyer 2008, Castillo 2017, FDA 2018, FDA 2021a, Holler 2011, Khan 2021, Schmuhl 2020, Warner 2016)

Adenosine/Caffeine and caffeine-containing products: Caffeine and caffeine-containing products may diminish the therapeutic effect of adenosine. Consider therapy modification.(Adenocard November 2009, Adenoscan November 2009, Aqel 2004, Reyes 2008, Rongen 1998, Smits 1990, Zoghbi 2006)

Sympathomimetics/Cocaine (topical): Cocaine (topical) may enhance the hypertensive effect of sympathomimetics. Consider therapy modification.(Ashchi 1995, Barnett 1998, Laffey 1999, Lormans 1992, McGovern 2015, Miller 1978, Nicholson 1995, Numbrino January 2020, Sundboll 2014)

Iohexol/Agents with seizure threshold–lowering potential: Agents with seizure threshold–lowering potential may enhance the adverse/toxic effect of iohexol. Specifically, the risk for seizures may be increased. Consider therapy modification.(Omnipaque July 2015)

Iomeprol/Agents with seizure threshold–lowering potential: Agents with seizure threshold–lowering potential may enhance the adverse/toxic effect of iomeprol. Specifically, the risk for seizures may be increased. Consider therapy modification.(Iomeron February 2009)

Iopamidol/Agents with seizure threshold–lowering potential: Agents with seizure threshold–lowering potential may enhance the adverse/toxic effect of iopamidol. Specifically, the risk for seizures may be increased. Consider therapy modification.(Isovue-M January 2017)

Sympathomimetics/Linezolid: Linezolid may enhance the hypertensive effect of sympathomimetics. Consider therapy modification.(Hendershot 2001, Zyvox June 2010)

Regadenoson/Caffeine and caffeine-containing products: Caffeine and caffeine-containing products may diminish the vasodilatory effect of regadenoson. Consider therapy modification.(Gaemperli 2008, Lexiscan October 2013, Tejani 2014, Zhao 2007)

Tizanidine/CYP1A2 inhibitors (weak): CYP1A2 inhibitors (weak) may increase the serum concentration of tizanidine. Consider therapy modification.(Granfors 2005, Zanaflex November 2013)

Amifampridine/Agents with seizure threshold–lowering potential: Agents with seizure threshold–lowering potential may enhance the neuroexcitatory and/or seizure-potentiating effect of amifampridine. Monitor therapy.(Firdapse November 2018)

Antipsychotic agents/Agents with seizure threshold–lowering potential: Agents with seizure threshold–lowering potential may enhance the adverse/toxic effect of antipsychotic agents. Specifically, the risk of seizures may be increased. Monitor therapy.(Abilify February 2020, Bonnet 2015, Caplyta April 2022, Clozapine July 2020, Deshauer 2000, Fanapt December 2010, Geodon January 2022, Haberfellner 2002, Hedges 2002, Invega December 2021, Latuda December 2019, Mahr 1987, Malek-Ahmadi 1988, Rexulti December 2021, Risperdal February 2021, Rucker 2008, Schmitz 2021, Secuado October 2019, Seroquel January 2022, Vraylar May 2019, Zyprexa October 2019)

Sympathomimetics/Atomoxetine: Atomoxetine may enhance the hypertensive effect of sympathomimetics. Atomoxetine may enhance the tachycardic effect of sympathomimetics. Monitor therapy.(Cantilena 2012, Hammerness 2009, Kelly 2005, Michelson 2003, Sofuoglu 2009, Spencer 2002, Strattera May 2017)

CYP1A2 substrates (high risk with inducers)/Broccoli: Broccoli may decrease the serum concentration of CYP1A2 substrates (high risk with inducers). Monitor therapy.(Bell 2000, McAlindon 2001, Rajoria 2011, Reed 2005)

Bromperidol/Caffeine and caffeine-containing products: Caffeine and caffeine-containing products may decrease the absorption of bromperidol. Monitor therapy.(Brom 2017)

Agents with seizure threshold–lowering potential/Bupropion: Bupropion may enhance the neuroexcitatory and/or seizure-potentiating effect of agents with seizure threshold–lowering potential. Monitor therapy.(Wellbutrin May 2017)

Sympathomimetics/Cannabinoid-containing products: Cannabinoid-containing products may enhance the tachycardic effect of sympathomimetics. Monitor therapy.(Benowitz 1977, Foltin 1987, Foltin 1990, Foltin 1995, Gash 1978, Kollins 2015, Lukas 1994, Williamson 2000)

CYP1A2 substrates (high risk with inducers)/Cannabis: Cannabis may decrease the serum concentration of CYP1A2 substrates (high risk with inducers). Monitor therapy.(Chetty 1994, Gardner 1983, Jusko 1978, Jusko 1979)

Clozapine/CYP1A2 inhibitors (weak): CYP1A2 inhibitors (weak) may increase the serum concentration of clozapine. Monitor therapy.(Al Hadithy 2012, Carrillo 1998, Clozaril February 2017, Gabbay 2002, Hagg 2000, Raaska 2004, Rajkumar 2013, Sandson 2007, Schoretsanitis 2020, Szymanski 1991, Vainer 1994)

Caffeine and caffeine-containing products/CYP1A2 inducers (moderate): CYP1A2 inducers (moderate) may decrease the serum concentration of caffeine and caffeine-containing products. Monitor therapy.(Aubagio September 2019, Cafcit December 2018)

Caffeine and caffeine-containing products/CYP1A2 inhibitors (moderate): CYP1A2 inhibitors (moderate) may increase the serum concentration of caffeine and caffeine-containing products. Monitor therapy.(Bapiro 2005, Bendriss 1996, Cafcit December 2018, Fexinidazole 2021, Harder 1988, Harder 1989, Healy 1989, Joeres 1987a, Joeres 1987b, Kim 2003, Kinzig-Schippers 1999, Mahr 1992, Mays 1987, Nicolau 1995, Staib 1987, Stille 1987, Tabrecta May 2020, Tantcheva-Poor 2001, Vassiliou 2021, Xiao 2019)

Caffeine and caffeine-containing products/CYP1A2 inhibitors (strong): CYP1A2 inhibitors (strong) may increase the serum concentration of caffeine and caffeine-containing products.(Cafcit December 2018, Christensen 2002, Croft 2012, Culm-Merdek 2005, Jeppesen 1996a, Jeppesen 1996b, Kashuba 1998, Ozdemir 1998, Qelbree April 2021, Spigset 1998, Yoshimura 2002)

CNS stimulants/Esketamine: Esketamine may enhance the hypertensive effect of CNS stimulants. Monitor therapy.(Spravato March 2019)

Formoterol/Caffeine and caffeine-containing products: Caffeine and caffeine-containing products may enhance the adverse/toxic effect of formoterol. Caffeine and caffeine-containing products may enhance the hypokalemic effect of formoterol. Monitor therapy.(Dulera June 2010)

Sympathomimetics/Guanethidine: Guanethidine may enhance the arrhythmogenic effect of sympathomimetics. Guanethidine may enhance the hypertensive effect of sympathomimetics. Monitor therapy.(Deshmankar 1967, Gulati 1966, Ismelin July 2014, Laurence 1963, Muelheims 1965, Simonyi 1972)

Halofantrine/Kola nut: Kola nut may decrease serum concentrations of the active metabolite(s) of halofantrine. Kola nut may decrease the serum concentration of halofantrine. Monitor therapy.(Kolade 2008)

Indacaterol/Caffeine and caffeine-containing products: Caffeine and caffeine-containing products may enhance the adverse/toxic effect of indacaterol. Caffeine and caffeine-containing products may enhance the hypokalemic effect of indacaterol. Monitor therapy.(Arcapta July 2011)

Lithium/Caffeine and caffeine-containing products: Caffeine and caffeine-containing products may decrease the serum concentration of lithium. Monitor therapy.(Jefferson 1988, Kralovec 2011, Mester 1995, Shirley 2002)

Caffeine and caffeine-containing products/Norfloxacin: Norfloxacin may increase the serum concentration of caffeine and caffeine-containing products. Monitor therapy.(Carbo 1989, Harder 1988)

Olodaterol/Caffeine and caffeine-containing products: Caffeine and caffeine-containing products may enhance the adverse/toxic effect of olodaterol. Caffeine and caffeine-containing products may enhance the hypokalemic effect of olodaterol. Monitor therapy.(Strierdi Respimat July 2014)

Sympathomimetics/Ozanimod: Ozanimod may enhance the hypertensive effect of sympathomimetics. Monitor therapy.(Tran 2020, Zeposia March 2020)

Caffeine and caffeine-containing products/Pipemidic acid: Pipemidic acid may increase the serum concentration of caffeine and caffeine-containing products. Monitor therapy.(Cafcit September 1999, Carbo 1989, Fuhr 1990, Harder 1988, Urotractin July 2017)

Solriamfetol/Sympathomimetics: Sympathomimetics may enhance the hypertensive effect of solriamfetol. Sympathomimetics may enhance the tachycardic effect of solriamfetol. Monitor therapy.(Sunosi June 2019)

Sympathomimetics/Sympathomimetics: Sympathomimetics may enhance the adverse/toxic effect of other sympathomimetics. Monitor therapy.(Foradil September 2001, Lidocaine April 2017, Maxa 2020, ProAmatine February 2017)

Sympathomimetics/Tedizolid: Tedizolid may enhance the hypertensive effect of sympathomimetics. Tedizolid may enhance the tachycardic effect of sympathomimetics. Monitor therapy.(Flanagan 2013, Hendershot 2001, Sivextro June 2014, Zyvox September 2013)

Theophylline derivatives/CYP1A2 inhibitors (weak): CYP1A2 inhibitors (weak) may increase the serum concentration of theophylline derivatives. Monitor therapy.(Bauman 1982, Campbell 1981, Cohen 1985, Colli 1987, Conrad 1980, Gardner 1983, Granneman 1995, Koren 1985, Lee 1992, Lofgren 1982, Loi 1989, Lombardi 1987, Maeda 1996, Miners 1985, Mojtahedzadeh 2003, Mulkey 1983, Niki 1987, Powell 1984, Sato 1993, Spinler 1993, Staib 1989, Theo-24 August 2017, Tornatore 1982, Vestal 1983, Wijnands 1986, Wijnands 1987, Williams 1987)

Caffeine and caffeine-containing products/Tobacco (smoked): Tobacco (smoked) may decrease the serum concentration of caffeine and caffeine-containing products. Monitor therapy.(Acheson 1987, Benowitz 2003, Brown 1988, Casto 1990, Cusack 1980, Cusack 1985, Eldon 1987, Faber 2004, Gardner 1983, Grygiel 1981, Hunt 1976, Joeres 1988, Jusko 1978, Lee 1987, Matsunga 1989, Mayo 2001, Miners 1985, Parsons 1978, Powell 1977, Samaan 1989)

Warfarin/Caffeine and caffeine-containing products: Caffeine and caffeine-containing products may diminish the anticoagulant effect of warfarin. Monitor therapy.(Clapauch 2012)

Caffeine and caffeine-containing products/CYP1A2 inducers (weak): CYP1A2 inducers (weak) may decrease the serum concentration of caffeine and caffeine-containing products. No action needed.(Dumond 2010, Kirby 2011, Magnusson 2008, Wietholtz 1989, Wietholz 1995)

Caffeine and caffeine-containing products/CYP1A2 inhibitors (weak): CYP1A2 inhibitors (weak) may increase the serum concentration of caffeine and caffeine-containing products. No action needed.(Abernethy 1985, Bachmann 2020, Balogh 1995, Beach 1986, Carbo 1989, Edwards 2017, Epidiolex October 2020, Harder 1988, Kinzig 1999, Mavyret April 2020, Michaud 2006, Olysio November 2017, Pegintron January 2019, Thai 2021)

Caffeine and caffeine-containing products/Hibiscus: Hibiscus may increase the serum concentration of caffeine and caffeine-containing products. No action needed.(Johnson 2013, Showande 2019)

Caffeine and caffeine-containing products/L-Theanine: L-theanine may diminish the therapeutic effect of caffeine and caffeine-containing products. Specifically, the vasoconstrictive and cognition- and mood-enhancing effects of caffeine may be diminished. L-theanine may enhance the therapeutic effect of caffeine and caffeine-containing products. Specifically, caffeine effects on cognition and neurophysiologic performance may be enhanced. No action needed.(Dodd 2015, Foxe 2012, Kahathuduwa 2017, Owen 2008)

Caffeine and caffeine-containing products/Menthol: Menthol may decrease the absorption of caffeine and caffeine-containing products. Specifically, menthol may delay absorption of caffeine. No action needed.(Begas 2017, Gelal 2003)

Monoamine oxidase inhibitors/Caffeine and caffeine-containing products: Caffeine and caffeine-containing products may enhance the hypertensive effect of monoamine oxidase inhibitors. No action needed.(Pakes 1979, van der Hoeven 2014)

Sympathomimetics/Procarbazine: Procarbazine may enhance the adverse/toxic effect of sympathomimetics. No action needed.(Matulane August 2018)

Caffeine and caffeine-containing products/Quercetin: Quercetin may increase the serum concentration of caffeine and caffeine-containing products. No action needed.(Chen 2009, Xiao 2014)

Caffeine and caffeine-containing products/Terbinafine (systemic): Terbinafine (systemic) may increase the serum concentration of caffeine and caffeine-containing products. No action needed.(Trepanier 1998, Wahllander 1989)

Adverse Reactions

Case reports and evidence from clinical studies are lacking. A report of increased gastric acid secretion in rodents exists; avoid use in individuals with known peptic ulcer.(Ibu 1986)


Kola nut has FDA GRAS status, and is used in the food industry.(FDA 2021b)

Subacute toxicity studies in rats showed findings consistent with methylxanthine toxicity, including restlessness, excitement, and irritability.(Burdock 2009)

A study in pregnant mice using high-dose kola nut reported a significant decrease in pup body weights.(Burdock 2009)

It has been suggested that the high amine content is possibly related to oral and GI cancers observed among habitual chewers of kola nut.(Atawodi 1995)

Primarily dose-dependent increases in blood pressure were observed in both normotensive and hypertensive rats, with diastolic pressure more sensitive to dose.(Igbinovia 2009) Increases in metabolic rate were noted in a rat study examining 3 species of kola nut, with C. accuminata having the greatest effect. Researchers also examined effects on isolated rat heart, noting increases in both force of contraction and rate with low doses of kola nut extract, with higher doses resulting in decreases in contraction and rate, until heart failure occurred.(Chukwu 2006)



This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol. 1985;28(4):425-428.4029248
Abilify (aripiprazole) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; February 2020.
Acebrophylline 100 mg capsule [KR prescribing information]. Accessed September 1, 2014.
Acheson DW, Uden S, Braganza JM, Brown SW, Houston JB. Theophylline and antipyrine disposition in smoking and non-smoking epileptic subjects. Br J Clin Pharmacol. 1987;24(6):812-815.3440101
Adaniya S, Takahashi M, Koyama K, Ogane K, Momose T. Two cases of decreased 123I-metaiodobenzylguanidine lung uptake in metaiodobenzylguanidine scintigraphy while taking selective serotonin reuptake inhibitor/serotonin noradrenaline reuptake inhibitor. Clin Nucl Med. 2021;46(4):329-331.33315681
Adenocard (adenosine) [prescribing information]. Deerfield, IL: Astellas Pharma US Inc; November 2009.
Adenoscan (adenosine) [prescribing information]. Deerfield, IL: Astellas Pharma US Inc; November 2009.
Adeyeye EI, Ayejuyo OO. Chemical composition of Cola acuminata and Garcinia kola seeds grown in Nigeria. Intl JFood SciNutr. 1994;45(4):223-230.
AdreView (iobenguane I 123) [prescribing information]. Arlington Heights, IL: GE Healthcare; March 2020.
Al Hadithy A, Leeffers E, Bruggeman R. Clozapine levels might be affected by excessive cola consumption. J Clin Psychopharmacol. 2012;32(5):717-719.22926611
Arcapta (indacaterol) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; July 2011.
Atawodi SE, Mende P, Pfundstein B, Preussmann R, Spiegelhalder B. Nitrosatable amines and nitrosamide formation in natural stimulants: Cola acuminata, C. nitida and Garcinia cola. Food Chem Toxicol. 1995;33(8):625-630. doi:10.1016/0278-6915(95)00035-z7672735
Aqel RA, Zoghbi GJ, Trimm JR, Baldwin SA, Iskandrian AE. Effect of caffeine administered intravenously on intracoronary-administered adenosine-induced coronary hemodynamics in patients with coronary artery disease. Am J Cardiol. 2004;93(3):343-346.14759387
Ashchi M, Wiedemann HP, James KB. Cardiac complication from use of cocaine and phenylephrine in nasal septoplasty. Arch Otolaryngol Head Neck Surg. 1995;121(6):681-684.7772323
Aubagio (teriflunomide) [prescribing information]. Cambridge, MA: Genzyme Corporation; September 2019.
Azedra (iobenguane I 131) [prescribing information]. New York, NY: Progenics Pharmaceuticals Inc; July 2018.
Bachmann F, Duthaler U, Meyer HE, et al. Metamizole is a moderate cytochrome P450 inducer via the constitutive androstane receptor and a weak inhibitor of CYP1A2 [published online December 17, 2020]. Clin Pharmacol Ther. doi:10.1002/cpt.214133336382
Balogh A, Klinger G, Henschel L, Borner A, Vollanth R, Kuhnz W. Influence of ethinylestradiol-containing combination oral contraceptives with gestodene or levonorgestrel on caffeine elimination. Eur J Clin Pharmacol. 1995;48(2):161-166.7589032
Bapiro TE, Sayi J, Hasler JA, et al. Artemisinin and thiabendazole are potent inhibitors of cytochrome P450 1A2 (CYP1A2) activity in humans. Eur J Clin Pharmacol. 2005;61(10):755-761.16261361
Barnett P. Cocaine toxicity following dermal application of adrenaline-cocaine preparation. Pediatr Emerg Care. 1998;14(4):280-281.9733253
Bauman JH, Kimelblatt BJ, Caraccio TR, Silverman HM, Simon GI, Beck GJ. Cimetidine-theophylline interaction: report of four patients. Ann Allergy. 1982;48(2):100-102.6121526
Beach CA, Mays DC, Guiler RC, Jacober CH, Gerber N. Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics. Clin Pharmacol Ther. 1986;39(3):265-270.3948467
Begas E, Tsioutsiouliti A, Kouvaras E, et al. Effects of peppermint tea consumption on the activities of CYP1A2, CYP2A6, xanthine oxidase, N-acetyltranferase-2 and UDP-glucuronosyltransferases-1A1/1A6 in healthy volunteers. Food Chem Toxicol. 2017;100:80-89.28011360
Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol. 2000;78(2):123-129.10926790
Bendriss EK, Bechtel Y, Bendriss A, et al. Inhibition of caffeine metabolism by 5-methoxypsoralen in patients with psoriasis. Br J Clin Pharmacol. 1996;41(5):421-424.8735685
Benowitz NL, Jones RT. Prolonged delta-9-tetrahydrocannabinol ingestion. Effects of sympathomimetic amines and autonomic blockades. Clin Pharmacol Ther. 1977;21:336-342.837652
Benowitz NL, Peng M, Jacob P 3rd. Effects of cigarette smoking and carbon monoxide on chlorzoxazone and caffeine metabolism. Clin Pharmacol Ther. 2003;74(5):468-474.14586387
Bonnet U, Taazimi B, Montag M, et al. Severe acute pancreatitis, neuroleptic malignant syndrome and grand mal seizures associated with elevated amisulpride and low clozapine serum levels. Psychiatr Danub. 2015;27(4):424-425.26609657
Boyer EW, Babu KM, Adkins JE, McCurdy CR, Halpern JH. Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction. 2008;103(6):1048-1050.18482427
Brom (bromperidol) [KR prescribing information]. Available at: Accessed October 27, 2017
Brown CR, Jacob P 3rd, Wilson M, Benowitz NL. Changes in rate and pattern of caffeine metabolism after cigarette abstinence. Clin Pharmacol Ther. 1988;43(5):488-491.3365914
Burdock GA, Carabin IG, Crincoli CM. Safety assessment of kola nut extract as a food ingredient. Food Chem Toxicol. 2009;47(8):1725-1732. doi:10.1016/j.fct.2009.04.01919394393
Cafcit (caffeine citrate) [prescribing information]. Befoed, OH: Ben Venue Laboratories, Inc; September 1999.
Cafcit (caffeine citrate) [prescribing information]. Eatontown, NJ: West-Ward Pharmaceuticals; December 2018.
Campbell MA, Plachetka JR, Jackson JE, Moon JF, Finley PR. Cimetidine decreases theophylline clearance. Ann Intern Med. 1981;95(1):68-69.7247131
Cantilena L, Kahn R, Duncan CC, Li SH, Anderson A, Elkashef A. Safety of atomoxetine in combination with intravenous cocaine in cocaine-experienced participants. J Addict Med. 2012;6(4):265-273.22987022
Caplyta (lumateperone) [prescribing information]. New York, NY: Intra-Cellular Therapies Inc; April 2022.
Carbo M, Segura J, De la Torre R, Badenas JM, Cami J. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther. 1989;45(3):234-240.2920498
Carrillo JA, Herraiz AG, Ramos SI, Benitez J. Effects of caffeine withdrawal from the diet on the metabolism of clozapine in schizophrenic patients. J Clin Psychopharmacol. 1998;18(4):311-316.9690697
Castillo A, Payne JD, Nugent K. Posterior reversible leukoencephalopathy syndrome after kratom ingestion. Proc (Bayl Univ Med Cent). 2017;30(3):355-357.28670086
Casto DT, Schnapf BM, Clotz MA. Lack of effect of short-term passive smoking on the metabolic disposition of theophylline. Eur J Clin Pharmacol. 1990;39(4):399-402.2076725
Chen Y, Xiao P, Ou-Yang DS, et al. Simultaneous action of the flavonoid quercetin on cytochrome P450 (CYP) 1A2, CYP2A6, N-acetyltransferase and xanthine oxidase activity in healthy volunteers. Clin Exp Pharmacol Physiol. 2009;36(8):828-833.19215233
Chetty M, Miller R, Moodley SV. Smoking and body weight influence the clearance of chlorpromazine. Eur J Clin Pharmacol. 1994;46(6):523-526.7995319
Christensen M, Tybring G, Mihara K, et al. Low daily 10-mg and 20-mg doses of fluvoxamine inhibit the metabolism of both caffeine (cytochrome P4501A2) and omeprazole (cytochrome P4502C19). Clin Pharmacol Ther. 2002;71(3):141-152.11907488
Chukwu LO, Odiete WO, Briggs LS. Basal metabolic regulatory responses and rhythmic activity of mammalian heart to aqueous kola nut extracts. African J Biotechnoly. 2006;5(5):484-486.
Clapauch SH, Benchimol-Barbosa PR. Warfarin resistance and caffeine containing beverages. Int J Cardiol. 2012;156(1):e4-e5.21852006
Clozapine [prescribing information]. Morgantown, WV: Mylan Pharmaceuticals Inc; July 2020.
Clozaril (clozapine) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; February 2017.
Cohen IA, Johnson CE, Berardi RR, Hyneck ML, Achem SR. Cimetidine-theophylline interaction: effects of age and cimetidine dose. Ther Drug Monit. 1985;7(4):426-434.4082242
Cola acuminata. USDA, NRCS. 2022. The PLANTS Database. ( 18 July 2022). National Plant Data Team, Greensboro, NC 27401-4901. USA
Colli A, Buccino G, Cocciolo M, Parravicini R, Elli GM, Scaltrini G. Ticlopidine-theophylline interaction. Clin Pharmacol Ther. 1987;41(3):358-362.3816023
Conrad KA, Nyman DW. Effects of metoprolol and propranolol on theophylline elimination. Clin Pharmacol Ther. 1980;28(4):463-467.7408406
Croft M, Keely B, Morris I, Tann L, Lappin G. Predicting drug candidate victims of drug-drug interactions, using microdosing. Clin Pharmacokinet. 2012;51(4):237-246.22335429
Culm-Merdek K, von Moltke L, Harmatz J, Greenblatt D. Fluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics. Br J Clin Pharmacol. 2005;60(5):486-493.16236038
Cusack BJ, Dawson GW, Mercer GD, Vestal RE. Cigarette smoking and theophylline metabolism: effects of cimetidine. Clin Pharmacol Ther. 1985;37(3):330-336.3971657
Cusack B, Kelly JG, Lavan J, Noel J, O'Malley K. Theophylline kinetics in relation to age: the importance of smoking. Br J Clin Pharmacol. 1980;10(2):109-114.7426272
Dah Nouvlessounon D, Adoukonou Sagbadja H, Diarrassouba N, et al. Antimicrobial, antioxidant, cytotoxic activities and phytochemical assessment of Cola Acuminata used in Benin. Int J PharmPharmaceut Sci. 2015;7(6):102-109.
Deshauer D, Albuquerque J, Alda M, Grof P. Seizures caused by possible interaction between olanzapine and clomipramine. J Clin Psychopharmacol. 2000;20(2):283-284.10770480
Deshmankar BS, Lewis JA. Ventricular tachycardia associated with the administration of methylphenidate during guanethidine therapy. Can Med Assoc J. 1967;97(19):1166-1167.6057135
Dodd FL, Kennedy DO, Riby LM, Haskell-Ramsay CF. A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood. Psychopharmacology (Berl). 2015;232(14):2563-2576.25761837
Doxofylline tablets [KR prescribing information]. Accessed December 15, 2015.
Dulera (mometasone/formoterol) [prescribing information]. Whitehouse Station, NJ: Merck & Co. Inc; June 2010.
Dumond JB, Vouvahis M, Rezk NL, et al. A phenotype-genotype approach to predicting CYP450 and P-glycoprotein drug interactions with the mixed inhibitor/inducer tipranavir/ritonavir. Clin Pharmacol Ther. 2010;87(6):735-742.20147896
Edwards JE, Eliot L, Parkinson A, Karan S, MacConell L. Assessment of pharmacokinetic interactions between obeticholic acid and caffeine, midazolam, warfarin, dextromethorphan, omeprazole, rosuvastatin, and digoxin in phase 1 studies in healthy subjects. Adv Ther. 2017;34(9):2120-2138.28808886
Ekalu A, Habila JD. Phytochemistry, pharmacology and medicinal uses of Cola (Malvaceae) family: a review. Med Chem Res. 2020;29:2089-2105.
Eldon MA, Luecker PW, MacGee J, Ritschel WA. Lack of effect of withdrawal from cigarette smoking on theophylline pharmacokinetics. J Clin Pharmacol. 1987;27(3):221-225.3680578
Epidiolex (cannabidiol) oral solution [prescribing information]. Carlsbad, CA: Greenwich Biosciences Inc; October 2020.
Estorch M, Carrio I, Mena E, et al. Challenging the neuronal MIBG uptake by pharmacological intervention: effect of a single dose of oral amitriptyline on regional cardiac MIBG uptake. Eur J Nucl Med Mol Imaging. 2004;31(12):1575-1580.15221292
Faber MS, Fuhr U. Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. Clin Pharmacol Ther. 2004;76(2):178-184.15289794
Fanapt (iloperidone) [prescribing information]. Rockville, MD: Vanda Pharmaceuticals Inc; December 2010.
Fexinidazole [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US LLC; July 2021.
Firdapse (amifampridine) [prescribing information]. Coral Gables, FL: Catalyst Pharmaceuticals Inc; November 2018.
Flanagan S, Bartizal K, Minassian SL, Fang E, Prokocimer P. In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions. Antimicrob Agents Chemother. 2013;57(7):3060-3066.23612197
Foltin RW, Fischman MW. The effects of combinations of intranasal cocaine, smoked marijuana, and task performance on heart rate and blood pressure. Pharmacol Biochem Behav. 1990;36:311-315.2162543
Foltin RW, Fischman MW, Levin FR. Cardiovascular effects of cocaine in humans: laboratory studies. Drug Alcohol Depend. 1995;37:193-210.7796714
Foltin RW, Fischman MW, Pedroso JJ, et al. Marijuana and cocaine interactions in humans: cardiovascular consequences. Pharmacol Biochem Behav. 1987;28:459-464.2829241
Foradil (formoterol) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; September 2001.
Foxe JJ, Morie KP, Laud PJ, Rowson MJ, de Bruin EA, Kelly SP. Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task. Neuropharmacology. 2012;62(7):2320-2327.22326943
Fuhr U, Wolff T, Harder S, et al. Quinolone inhibition of cytochrome P-450-dependent caffeine metabolism in human liver microsomes. Drug Metab Dispos. 1990;18(6):1005-1010.1981505
Gabbay V, O'Dowd MA, Mamamtavrishvili M, Asnis GM. Clozapine and oral contraceptives: a possible drug interaction. J Clin Psychopharmacol. 2002;22(6):621-622.12454563
Gaemperli O, Schepis T, Koepfli P, et al. Interaction of caffeine with regadenoson-induced hyperemic myocardial blood flow as measured by positron emission tomography. J Am Coll Cardiol. 2008;51(3):328-329.18206744
Gardner MJ, Tornatore KM, Jusko WJ, Kanarkowski R. Effects of tobacco smoking and oral contraceptive use on theophylline disposition. Br J Clin Pharmacol. 1983;16(3):271-280.6626419
Gash A, Karliner JS, Janowsky D, et al. Effects of smoking marihuana on left ventricular performance and plasma norepinephrine: studies in normal men. Ann Intern Med. 1978;89:448-452.697222
Gelal A, Guven H, Balkan D, Artok L, Benowitz NL. Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers. Eur J Clin Pharmacol. 2003;59(5-6):417-422.12915954
Geodon (ziprasidone) [prescribing information]. New York, NY: Pfizer Inc; January 2022.
Granfors MT, Backman JT, Laitila J, Neuvonen PJ. Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2. Clin Pharmacol Ther. 2005;78(4):400-411.16198659
Granneman GR, Braeckman RA, Locke CS, Cavanaugh JH, Dube LM, Awni WM. Effect of zileuton on theophylline pharmacokinetics. Clin Pharmacokinet. 1995;29(suppl 2):77-83.8620674
Grygiel JJ, Birkett DJ. Cigarette smoking and theophylline clearance and metabolism. Clin Pharmacol Ther. 1981;30(4):491-496.7285483
Gulati OD, Dave BT, Gokhale SD, Shah KM. Antagonism of adrenergic neuron blockade in hypertensive subjects. Clin Pharmacol Ther. 1966;7(4):510-514.5939974
Haberfellner EM. Myoclonic and generalized tonic clonic seizures during combined treatment with low doses of clozapine and haloperidol. Eur Psychiatry. 2002;17(1):55-56.11918994
Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2000;49(1):49-63.10606838
Hammerness P, Georgiopoulos A, Doyle RL, et al. An open study of adjunct OROS-methylphenidate in children who are atomoxetine partial responders: II. Tolerability and pharmacokinetics. J Child Adolesc Psychopharmacol. 2009;19(5):493-499.19877973
Harder S, Fuhr U, Staib AH, Wolff T. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med. 1989;87(5A):89S-91S.2589393
Harder S, Staib AH, Beer C, Papenburg A, Stille W, Shah PM. 4-quinolones inhibit biotransformation of caffeine. Eur J Clin Pharmacol. 1988;35(6):651-656.2853056
Healy DP, Polk RE, Kanawati L, Rock DT, Mooney ML. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother. 1989;33(4):474-478.2729942
Hedges DW, Jeppson KG. New-onset seizure associated with quetiapine and olanzapine. Ann Pharmacother. 2002;36(3):437-439.11895056
Hendershot PE, Antal EJ, Welshman IR, et al. Linezolid: pharmacokinetic and pharmacodynamic evaluation of coadministration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorpan HBr. J Clin Pharmacol. 2001;41(5):563-572.11361053
Holler JM, Vorce SP, McDonough-Bender PC, Magluilo J Jr, Solomon CJ, Levine B. A drug toxicity death involving propylhexedrine and mitragynine. J Anal Toxicol. 2011;35(1):54-59.21219704
Hunt SN, Jusko WJ, Yurchak AM. Effect of smoking on theophylline disposition. Clin Pharmacol Ther. 1976;19(5, pt 1):546-551.1277710
Ibu JO, Iyama AC, Ijije CT, Ishmael D, Ibeshi M, Nwokediuko S. The effect of Cola acuminata and Cola nitida on gastric acid secretion. Scand J Gastroenterol Suppl. 1986;124:39-45. doi:10.3109/003655286090937803508643
Igbinovia ENS, Ugwu AC, Nwaopara AO, et al. The effects of Cola acuminata on arterial blood pressure. Pakistan J Nutr. 2009;8(2):148-150.
Invega (paliperidone) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc; December 2021.
Iomeron (iomeprol) [summary of product characteristics]. Sydney, New South Wales: Bracco Pty Ltd; February 2009.
Ismelin (guanethidine) [summary of product characteristics]. Basildon, Essex, UK: Amdipharm UK Limited; July 2014.
Isovue-M (iopamidol) [prescribing information]. Princeton, NJ: Bracco Diagnostics Inc; January 2017.
Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry. 1988;49(2):72-73.3338980
Jeppesen U, Gram L, Vistisen K, Loft S, Poulsen H, Brosen K. Dose-dependent inhibition of CYP1A2, CYP2C19, and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine. Eur J Clin Pharmacol. 1996;51(1):73-78.8880055
Jeppesen U, Loft S, Poulsen H, Brosen K. A fluvoxamine-caffeine interaction study. Pharmacogenetics. 1996;6(3):213-222.8807660
Joeres R, Klinker H, Heusler H, Epping J, Richter E. Influence of mexiletine on caffeine elimination. Pharmacol Ther. 1987;33(1):163-169.3628469
Joeres R, Klinker H, Heusler H, Epping J, Zilly W, Richter E. Influence of smoking on caffeine elimination in healthy volunteers and in patients with alcoholic liver cirrhosis. Hepatology. 1988;8(3):575-579.3371873
Joeres R, Richter E. Mexiletine and caffeine elimination. N Engl J Med. 1987;317(2):117.3587324
Johnson SS, Oyelola FT, Ari T, Juho H. In vitro inhibitory activities of the extract of Hibiscus sabdariffa L. (family Malvaceae) on selected cytochrome P450 isoforms. Afr J Tradit Complement Altern Med. 2013;10(3):533-540.24146485
Jusko WJ, Gardner MJ, Mangione A, Schentag JJ, Koup JR, Vance JW. Factors affecting theophylline clearances: age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates, and ethanol. J Pharm Sci. 1979;68(11):1358-1366.41932
Jusko WJ, Schentag JJ, Clark JH, Gardner M, Yurchak AM. Enhanced biotransformation of theophylline in marihuana and tobacco smokers. Clin Pharmacol Ther. 1978;24(4):405-410.688731
Kahathuduwa CN, Dassanayake TL, Amarakoon AMT, Weerasinghe VS. Acute effects of theanine, caffeine and theanine-caffeine combination on attention. Nutr Neurosci. 2017;20(6):369-377.26869148
Kamatenesi-Mugisha M, Oryem-Origa H. Traditional herbal remedies used in the management of sexual impotence and erectile dysfunction in western Uganda. Afr Health Sci. 2005;5(1):40-49.15843130
Kashuba A, Nafziger A, Kearns G, et al. Effect of fluvoxamine therapy on the activities of CYP1A2, CYP2D6, and CYP3A as determined by phenotyping. Clin Pharmacol Ther. 1998;64(3):257-268.9757149
Kelly RP, Yeo KP, Teng CH, et al. Hemodynamic effects of acute administration of atomoxetine and methylphenidate. J Clin Pharmacol. 2005;45:851-855.15951476
Khan MZ, Saleh MA, Alkhayyat M, Roberts DE, Lindenmeyer CC. Multiorgan dysfunction related to Kratom ingestion. ACG Case Rep J. 2021;8(8):e00647.34476274
Kim MK, Nightingale C, Nicolau D. Influence of sex on the pharmacokinetic interaction of fleroxacin and ciprofloxacin with caffeine. Clin Pharmacokinet. 2003;42(11):985-996.12908854
Kinzig-Schippers M, Fuhr U, Zaigler M, et al. Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2. Clin Pharmacol Ther. 1999;65(3):262-274.10096258
Kirby BJ, Collier AC, Kharasch ED, et al. Complex drug interactions of HIV protease inhibitors 2: in vivo induction and in vitro to in vivo correlation of induction of cytochrome P450 1A2, 2B6, and 2C9 by ritonavir or nelfinavir. Drug Metab Dispos. 2011;39(12):2329-2337.21930825
Kolade YT, Babalola CP, Olaniyi AA, Scriba GKE. Effect of kolanut on the pharmacokinetics of the antimalarial drug halofantrine. Eur J Clin Pharmacol. 2008;64(1):77-81.17952423
Kollins SH, Schoenfelder EN, English JS, et al. An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults. J Subst Abuse Treat. 2015;48(1):96-103.25175495
Koren G, Chin TF, Correia J, Tesoro A, MacLeod SM. Theophylline pharmacokinetics in adolescent females following coadministration of oral contraceptives. Clin Invest Med. 1985;8(3):222-226.4042465
Kralovec K, Fartacek R, Ploderl M, Fartacek C, Aichhorn W. Low serum lithium associated with immoderate use of Coca-Cola Zero. J Clin Psychopharmacol. 2011;31(4):543-544.21720234
Laffey JG, Neligan P, Ormonde G. Prolonged perioperative myocardial ischemia in a young male: due to topical intranasal cocaine? J Clin Anesth. 1999;11(5):419-424.10526815
Latuda (lurasidone) [prescribing information]. Marlborough, MA: Sunovion Pharmaceuticals Inc; December 2019.
Laurence DR, Nagle RE. The effects of bretylium and guanethidine on the pressor responses to noradrenaline and angiotensin. Br J Pharmacol Chemother. 1963;21:403-413.14110739
Lee BL, Benowitz NL, Jacob P 3rd. Cigarette abstinence, nicotine gum, and theophylline disposition. Ann Intern Med. 1987;106(4):553-555.3826954
Lee BL, Dohrmann ML. Theophylline toxicity after propafenone treatment: evidence for drug interaction. Clin Pharmacol Ther. 1992;51(3):353-355.1544292
Lexiscan (regadenoson) [prescribing information]. Northbrook, IL: Astellas Pharma US Inc; October 2013.
Lidocaine 5% w/v and phenylephrine 0.5% w/v topical solution [product labeling]. Buckinghamshire, UK: Martindale Pharma; April 2017.
Lofgren RP, Gilbertson RA. Cimetidine and theophylline. Ann Intern Med. 1982;96(3):378.6800293
Loi CM, Day JD, Jue SG, et al. Dose-dependent inhibition of theophylline metabolism by disulfiram in recovering alcoholics. Clin Pharmacol Ther. 1989;45(5):476-486.2721103
Lombardi TP, Bertino JS Jr, Goldberg A, Middleton E Jr, Slaughter RL. The effects of a beta-2 selective adrenergic agonist and a beta-nonselective antagonist on theophylline clearance. J Clin Pharmacol. 1987;27(7):523-529.2888791
Lormans P, Gaumann D, Schwieger I, Tassonyi E. Ventricular fibrillation following local application of cocaine and epinephrine for nasal surgery. ORL J Otorhinolaryngol Relat Spec. 1992;54(3):160-162.1518666
Lukas SE, Sholar M, Kouri E, et al. Marihuana smoking increases plasma cocaine levels and subjective reports of euphoria in male volunteers. Pharmacol Biochem Behav. 1994;48:715-721.7938127
Maeda Y, Konishi T, Omoda K, et al. Inhibition of theophylline metabolism by aciclovir. Biol Pharm Bull. 1996;19(12):1591-1595.8996645
Magnusson MO, Dahl ML, Cederberg J, Karlsson MO, Sandstrom R. Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin. Clin Pharmacol Ther. 2008;84(1):52-62.17971810
Mahr G, Sorgel F, Granneman GR, et al. Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine. Clin Pharmacokinet. 1992;22(1):90-97.1319876
Mahr GC, Berchou R, Balon R. A grand mal seizure associated with desipramine and haloperidol. Can J Psychiatry. 1987;32(6):463-464.3121163
Malek-Ahmadi P. A grand mal seizure associated with desipramine and haloperidol. Can J Psychiatry. 1988;33(1):76-77.3129174
Matsunga SK, Plezia PM, Karol MD, Katz MD, Camilli AE, Benowitz NL. Effects of passive smoking on theophylline clearance. Clin Pharmacol Ther. 1989;46(4):399-407.2791443
Matulane (procarbazine) [prescribing information]. Gaithersburg, MD: Leadiant Biosciences; August 2018.
Maurice MI. Pharmacognostical Profile of Selected Medicinal Plants. In: Handbook of African Medicinal Plants. CRC Press; 2014.
Mavyret (glecaprevir and pibrentasvir) [prescribing information]. North Chicago, IL: AbbVie Inc; April 2020.
Maxa JL. Serotonin syndrome following terbutaline administration in a heart transplant patient on multiple inotropic agents: a case report. Transplant Proc. 2020;52(9):2817-2819.32560969
Mayo PR. Effect of passive smoking on theophylline clearance in children. Ther Drug Monit. 2001;23(5):503-505.11591894
Mays DC, Camisa C, Cheney P, Pacula CM, Nawoot S, Gerber N. Methoxsalen is a potent inhibitor of the metabolism of caffeine in humans. Clin Pharmacol Ther. 1987;42(6):621-626.3690940
McAlindon TE, Gulin J, Chen T, Klug T, Lahita R, Nuite M. Indole3-carbinol in women with SLE: effect on estrogen metabolism and disease activity. Lupus. 2001;10(11):779-783.11789487
McGovern E, Moylett E, McMahon CJ. Myocardial ischaemia following cocaine and adrenaline exposure in a child during an ophthalmological procedure. Ir Med J. 2015;108(3):89-90.25876303
Mester R, Toren P, Mizrachi I, Wolmer L, Karni N, Weizman A. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry. 1995;37(5):348-350.7748990
Michaud V, Mouksassi MS, Labbe L, et al. Inhibitory effects of propafenone on the pharmacokinetics of caffeine in humans. Ther Drug Monit. 2006;28(6):779-783.17164694
Michelson D, Adler L, Spencer T, et al. Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Biol Psychiatry. 2003;53:112-120.12547466
Miller SA, Mieler WF. Systemic reaction to subconjunctival phenylephrine. Can J Ophthalmol. 1978;13(4):290-293.743613
Miners JO, Attwood J, Wing LM, Birkett DJ. Influence of cimetidine, sulfinpyrazone, and cigarette smoking on theobromine metabolism in man. Drug Metab Dispos. 1985;13(5):598-601.2865110
Miners JO, Wing LM, Lillywhite KJ, Robson RA. Selectivity and dose-dependency of the inhibitory effect of propranolol on theophylline metabolism in man. Br J Clin Pharmacol. 1985;20(3):219-223.4041342
Mojtahedzadeh M, Sadray S, Hadjibabaie M, Fasihi M, Rezaee S. Determination of theophylline clearance after cimetidine infusion in critically ill patients. J Infus Nurs. 2003;26(4):234-238.12869856
Muelheims GH, Entrup RW, Paiewonsky D, Mierzwiak DS. Increased sensitivity of the heart to catecholamine-induced arrhythmias following guanethidine. Clin Pharmacol Ther. 1965;6(6):757-762.5846408
Mulkey PM, Murphy JE, Shleifer NH. Steady-state theophylline pharmacokinetic during and after short-term cimetidine administration. Clin Pharm. 1983;2(5):439-441.6627870
Muraoka T, Oku E, Sugataka S, Yamada S. A case of severe parkinsonism associated with short-term treatment with milnacipran. Clin Neuropharmacol. 2008;31(5):299-300.18836350
Nakajo M, Shapiro B, Sisson JC, Swanson DP, Beierwaltes WH. Salivary gland accumulation of meta-[131I]iodobenzylguanidine. J Nucl Med. 1984;25(1):2-6.6726418
Nicholson KE, Rogers JE. Cocaine and adrenaline paste: a fatal combination? BMJ. 1995;311(6999):250-251.7627047
Nicolau DP, Nightingale CH, Tessier PR, et al. The effect of fleroxacin and ciprofloxacin on the pharmacokinetics of multiple dose caffeine. Drugs. 1995;49(suppl 2):357-359.8549360
Niki Y, Soejima R, Kawane H, Sumi M, Umeki S. New synthetic quinolone antibacterial agents and serum concentration of theophylline. Chest. 1987;92(4):663-669.3477409
Numbrino (cocaine hydrochloride) nasal solution [prescribing information]. Philadelphia, PA: Lannett Company Inc; January 2020.
Oboh G, Akinyemi AJ, Omojokun OS, Oyeleye IS. Anticholinesterase and antioxidative properties of aqueous extract of Cola acuminata seed in vitro. Int J Alzheimers Dis. 2014;2014:498629. doi:10.1155/2014/49862925506036
Ojo OA, Ojo AB, Maimako RF, et al. Exploring the potentials of some compounds from Garcinia kola seeds towards identification of novel PDE-5 inhibitors in erectile dysfunction therapy. Andrologia. 2021;53(7):e14092. doi:10.1111/and.1409233945159
Olysio (simeprevir) [prescribing information]. Titusville, NJ: Janssen Therapeutics; November 2017.
Omnipaque (iohexol) [prescribing information]. Princeton, NJ: GE Healthcare Inc; July 2015.
Owen GN, Parnell H, De Bruin EA, Rycroft JA. The combined effects of L-thanine and caffeine on cognitive performance and mood. Nutr Neurosci. 2008;11(4):193-198.18681988
Ozdemir V, Naranjo C, Shulman R, et al. Determinants of interindividual variability and extent of CYP2D6 and CYP1A2 inhibition by paroxetine and fluvoxamine in vivo. J Clin Psychopharmacol. 1998;18(3):198-207.9617978
Pakes GE. Phenelzine-cola headache. Am J Hosp Pharm. 1979;36(6):736.463881
Parsons WD, Neims AH. Effect of smoking on caffeine clearance. Clin Pharmacol Ther. 1978;24(1):40-45.657717
Pegintron (peginterferon alfa-2b) [prescribing information]. Whitehouse Station, NJ: Merck & Co Inc; January 2019.
Powell JR, Rogers JF, Wargin WA, Cross RE, Eshelman FN. Inhibition of theophylline clearance by cimetidine but not ranitidine. Arch Intern Med. 1984;144(3):484-486.6322709
Powell JR, Thiercelin JF, Vozeh S, Sansom L, Riegelman S. The influence of cigarette smoking and sex on theophylline disposition. Am Rev Respir Dis. 1977;116(1):17-23.879596
ProAmatine (midodrine) [prescribing information]. Lexington, MA: Shire US Inc; February 2017.
Qelbree (viloxazine) [prescribing information]. Winchester, KY: Catalent Pharma Solutions LLC; April 2021.
Raaska K, Raitasuo V, Laitila J, Neuvonen P. Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalized patients. Basic Clin Pharmacol Toxicol. 2004;94(1):13-18.14725610
Rajkumar AP, Poonkuzhali B, Kuruvilla A, Jacob M, Jacob KS. Clinical predictors of serum clozapine levels in patients with treatment-resistant schizophrenia. Int Clin Psychopharmacol. 2013;28(1):50-56.23104241
Rajoria S, Suriano R, Parmar PS, et al. 3,3'-diindolymethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study. Thyroid. 2011;21(3):299-304.21254914
Reed GA, Peterson KS, Smith HJ, et al. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomarkers Prev. 2005;14(8):1953-1960.16103443
Rexulti (brexpiprazole) [prescribing information]. Deerfield, IL: Lundbeck; December 2021.
Reyes E, Loong CY, Harbinson M, Donovan J, Anagnostopoulos C, Underwood SR. High-dose adenosine overcomes the attenuation of myocardial perfusion reserve caused by caffeine. J Am Coll Cardiol. 2008;52(24):2008-2016.19055993
Risperdal (risperidone) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc.; February 2021.
Rongen GA, Brooks SC, Ando S, Notarius CF, Floras JS. Caffeine abstinence augments the systolic blood pressure response to adenosine in humans. Am J Cardiol. 1998;81(11):1382-1385.9631984
Rucker J, Cook M. A case of prolonged seizure after ECT in a patient treated with clomipramine, lithium, L-tryptophan, quetiapine, and thyroxine for major depression. J ECT. 2008;24(4):272-274.18648320
Samaan S, Fox R. The effect of smoking on theophylline kinetics in healthy and asthmatic elderly males. J Clin Pharmacol. 1989;29(5):448-450.2738176
Sandson NB, Cozza KL, Armstrong SC, Eckermann G, Fischer BA, Phillips B. Clozapine case series. Psychosomatics. 2007;48(2):170-175.17329613
Sato J, Nakata H, Owda E, Kikuta T, Umetsu M, Ito K. Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects. Eur J Clin Pharmacol. 1993;44(3):295-298.8491248
Schmitz A, Botner B, Hund M. Bupropion with clozapine: case reports of seizure after coadministration. J Pharm Pract. 2021;34(3):497-502.32079452
Schmuhl KK, Gardner SM, Cottrill CB, Bonny AE. Home induction and outpatient treatment of kratom use disorder with buprenorphine-naloxone: A case report in a young adult. Subst Abus. 2020;41(3):311-314.31644379
Schoretsanitis G, Kane JM, de Leon J. Adding oral contraceptives to clozapine may require halving the clozapine dose: a new case and a literature review. J Clin Psychopharmacol. 2020;40(3):308-310.32332470
Secuado (asenapine) [prescribing information]. Miami, FL: Noven Therapeutics, LLC; October 2019.
Seroquel (quetiapine) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; January 2022.
Shirley DG, Walter SJ, Noormohamed FH. Natriuretic effect of caffeine: assessment of segmental sodium reabsorption in humans. Clin Sci (Lond). 2002;103(5):461-466.12401118
Showande JS, Igbinoba SI, Kajula M, et al. In vitro modulation of cytochrome P450 isozymes and pharmacokinetics of caffeine by extracts of Hibiscus sabdariffa Linn calyx. J Basic Clin Physiol Pharmacol. 2019;30(3).30951501
Simonyi J, Krassoi A, Decsy J, et al. Guanethidine (Sanotensin)-induced changes in alpha and beta receptor sensitivity. Ther Hung. 1972;20(1):47-55.5057665
Sivextro (tedizolid phosphate) [prescribing information]. Lexington, MA: Cubist Pharmaceuticals US; June 2014.
Skarupova D, Vostalova J, Rajnochova Svobodova A. Ultraviolet A protective potential of plant extracts and phytochemicals. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2020;164(1):1-22. doi:10.5507/bp.2020.01032188958
Smits P, Lenders JW, Thien T. Caffeine and theophylline attenuate adenosine-induced vasodilation in humans. Clin Pharmacol Ther. 1990;48(4):410-418.2225701
Smits P, Schouten J, Thien T. Cardiovascular effects of two xanthines and the relation to adenosine antagonism. Clin Pharmacol Ther. 1989;45(6):593-599.2659234
Sofuoglu M, Poling J, Hill K, Kosten T. Atomoxetine attenuates dextroamphetamine effects in humans. Am J Drug Alcohol Abuse. 2009;35(6):412-416.20014909
Spencer T, Heiligenstein JH, Biderman J, et al. Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2002;63(12):1140-1147.12523874
Spigset O. Are adverse drug reactions attributed to fluvoxamine caused by concomitant intake of caffeine? Eur J Clin Pharmacol. 1998;54(8):665-666.9860156
Spinler SA, Gammaitoni A, Charland SL, Hurwitz J. Propafenone-theophylline interaction. Pharmacotherapy. 1993;13(1):68-71.8437970
Spravato (esketamine) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc; March 2019.
Staib AH, Harder S, Fuhr U, Wack C. Interaction of quinolones with the theophylline metabolism in man: investigations with lomefloxacin and pipemidic acid. Int J Clin Pharmacol Ther Toxicol. 1989;27(6):289-293.2737798
Staib AH, Stille W, Dietlein G, et al. Interaction between quinolones and caffeine. Drugs. 1987;34(suppl 1):170-174.3481318
Stille W, Harder S, Mieke S, et al. Decrease of caffeine elimination in man during co-administration of 4-quinolones. J Antimicrob Chemother. 1987;20(5):729-734.3480885
Strattera (atomoxetine) [prescribing information]. Indianapolis, IN: Lilly USA, LLC; May 2017.
Striverdi Respimat (olodaterol) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; July 2014.
Sundboll J, Pareek M, Hogsbro M, Madsen EH. Iatrogenic takotsubo cardiomyopathy induced by locally applied epinephrine and cocaine. BMJ Case Rep. 2014;2014.24554679
Sunosi (solriamfetol) [prescribing information]. Palo Alto, CA: Jazz Pharmaceuticals Inc; June 2019.
Szymanski S, Lieberman JA, Picou D, Masiar S, Cooper T. A case report of cimetidine-induced clozapine toxicity. J Clin Psychiatry. 1991;52(1):21-22.1988413
Tabrecta (capmatinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; May 2020.
Tantcheva-Poor I, Servera-Llaneras M, Scharffetter-Kochanek K, Fuhr U. Liver cytochrome P450 CYP1A2 is markedly inhibited by systemic but not by bath PUVA in dermatological patients. Br J Dermatol. 2001;144(6):1127-1132.11422031
Tejani FH, Thompson RC, Kristy R, Bukofzer S. Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson pharmacologic stress: a prospective, randomized, multicenter study. Int J Cardiovasc Imaging. 2014;30(5):979-989.24737255
Thai C, Tayo B, Critchley D. A phase I open-label, fixed sequence pharmacokinetic drug interaction trial to investigate the effect of cannabidiol on the CYP1A2 probe caffeine in healthy subjects. Clin Pharmacol Drug Dev. 2021;10(11):1279-1289.33951339
Theo-24 (theophylline anhydrous) [prescribing information]. Malvern, PA; Endo Pharmaceuticals Inc; August 2017.
Tornatore KM, Kanarkowski R, McCarthy TL, Gardner MJ, Yurchak AM, Jusko WJ. Effect of chronic oral contraceptive steroids on theophylline disposition. Eur J Clin Pharmacol. 1982;23(2):129-134.7140802
Tran JQ, Zhang P, Walker S, et al. Multiple-dose pharmacokinetics of ozanimod and its major active metabolites and the pharmacodynamic and pharmacokinetic interactions with pseudoephedrine, a sympathomimetic agent, in healthy subjects. Adv Ther. 2020;37(12):4944-4958.33025342
Trepanier EF, Nafziger AN, Kearns GL, Kashuba AD, Amsden GW. Absence of effect of terbinafine on the activity of CYP1A2, NAT-2, and xanthine oxidase. J Clin Pharmacol. 1998;38(5):424-428.9602954
Urotractin [SG product information]. Bangdung, Indonesia: Pt Sanbe Farma; received July 17, 2017.
US Food and Drug Administration. FDA and kratom. Accessed September 15, 2021.
US Food and Drug Administration. Food Additive Status List. Last reviewed August 26, 2021.
US Food and Drug Administration. Statement from FDA Commissioner Scott Gottlieb, M.D. on FDA advisory about deadly risks associated with kratom. Last reviewed April 5, 2018. Accessed September 15, 2021.
Vainer JL, Chouinard G. Interaction between caffeine and clozapine. J Clin Psychopharmacol. 1994;14(4):284-285.7962690
van der Hoeven N, Visser I, Schene A, van den Born BJ. Severe hypertension related to caffeinated coffee and tranylcypromine: a case report. Ann Intern Med. 2014;160(9):657-658.24798537
Vassiliou D, Sardh E, Harper P, et al. A drug-drug interaction study evaluating the effect of givosiran, a small interfering ribonucleic acid, on cytochrome P450 activity in the liver. Clin Pharmacol Ther. 2021;110(5):1250-1260.34510420
Vestal RE, Thummel KE, Musser B, Mercer GD. Cimetidine inhibits theophylline clearance in patients with chronic obstructive pulmonary disease: a study using stable isotope methodology during multiple oral dose administration. Br J Clin Pharmacol. 1983;15(4):411-418.6849776
Vraylar (cariprazine) [prescribing information]. Madison, NJ: Allergan USA Inc; May 2019.
Wahllander A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur J Clin Pharmacol. 1989;37(3):279-283.2612543
Warner ML, Kaufman NC, Grundmann O. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse. Int J Legal Med. 2016;130(1):127-138.26511390
Wellbutrin XL (bupropion) [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; May 2017.
Wietholtz H, Zysset T, Kreiten K, Kohl D, Buchsel R, Matern S. Effect of phenytoin, carbamazepine, and valproic acid on caffeine metabolism. Eur J Clin Pharmacol. 1989;36(4):401-406.2500346
Wietholtz H, Zysset T, Marschall HU, Generet K, Matern S. The influence of rifampin treatment on caffeine clearance in healthy man. J Hepatol. 1995;22(1):78-81.7751591
Wijnands WJ, Vree TB, Baars AM, van Herwaarden CL. The influence of the 4-quinolones ciprofloxacin, pefloxacin and ofloxacin on the elimination of theophylline. Pharm Weekbl Sci. 1987;11(9 suppl):S72-S75.3481439
Wijnands WJ, Vree TB, van Herwaarden CL. The influence of quinolone derivatives on theophylline clearance. Br J Clin Pharmacol. 1986;22(6):677-683.3567014
Williams SJ, Baird-Lambert JA, Farrell GC. Inhibition of theophylline metabolism by interferon. Lancet. 1987;24(2):939-941.2444839
Williamson EM, Evans FJ. Cannabinoids in clinical practice. Drugs. 2000;60(6):1303-1314.11152013
Xiao J, Huang WH, Peng JB, et al. Quercetin significantly inhibits the metabolism of caffeine, a substrate of cytochrome P450 1A2 unrelated to CYP1A2*1C (-2964G > A) and *1F (734C > A) gene polymorphisms. Biomed Res Int. 2014:405071.25025048
Xiao JJ, Nowak D, Ramlau R, et al. Evaluation of drug-drug interactions of rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P-gp substrates in patients with an advanced solid tumor. Clin Transl Sci. 2019;12(1):58-65.30427584
Yokoyama K, Yamada T, Terachi S, et al. Milnacipran influences the indexes of I-metaiodobenzylguanidine scintigraphy in elderly depressed patients. Psychiatry Clin Neurosci. 2014;68(3):169-175.24895731
Yoshimura R, Ueda N, Nakamura J, Eto S, Matsushita M. Interaction between fluvoxamine and cotinine or caffeine. Neuropsychobiology. 2002;45(1):32-35.11803239
Zanaflex (tizanidine) [prescribing information]. Ardsley, NY: Acorda Therapeutics Inc; November 2013.
Zeposia (ozanimod) [prescribing information]. Summit, NJ: Celgene Corporation; March 2020.
Zhao G, Messina E, Xu X, et al. Caffeine attenuates the duration of coronary vasodilation and changes in hemodynamics induced by regadenoson (CVT-3146), a novel adenosine A2A receptor agonist. J Cardiovasc Pharmacol. 2007;49(6):369-375.17577101
Zoghbi GJ, Htay T, Aqel R, Blackmon L, Heo J, Iskandrian AE. Effect of caffeine on ischemia detection by adenosine single-photon emission computed tomography perfusion imaging. J Am Coll Cardiol. 2006;47(11):2296-2302.16750699
Zyprexa (olanzapine) [prescribing information]. Indianapolis, IN: Lilly USA, LLC: October 2019.
Zyvox (linezolid) [prescribing information]. New York, NY: Pfizer Inc; September 2013.
Zyvox (linezolid) [prescribing information]. New York, NY: Pharmacia and Upjohn Company, June 2010.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.