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Caffeine Consumption, Withdrawal and Cerebral Blood Flow
Abstract
SYNOPSIS Regional cerebral blood flow (CBF) measurements were conducted under resting conditions and after twenty‐four hours of caffeine abstinence in groups of high and low caffeine users. CBF was also measured thirty minutes after the oral administration of 250 rag. of caffeine in the high caffeine users and after a placebo in the low caffeine users. Caffeine administration was associated with significant CBF reduction and caffeine abstinence with significant frontal flow increases in the high caffeine group. The low caffeine group showed no differences between the resting, post‐placebo and post‐caffeine abstinence CBF values.
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“Earlier, Mathew et al. demonstrated that cerebral blood flow decreases with caffeine ingestion [13,40].”
From Central and peripheral effects of sustained caffeine use: tolerance is incomplete (2002) · cites this paper as [40]
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Fredholm, B. B., Bättig, K., Holmén, J., Nehlig, A., & Zvartau, E. E. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01396-6 · Cited by 2,624
“This decrease can be achieved in humans after the absorption of 250 mg of caffeine (Mathew and Wilson, 1985; Cameron et al., 1990).”
Nehlig, A., Daval, J., & Debry, G. (1992) · Brain Research Reviews · doi:10.1016/0165-0173(92)90012-b · Cited by 1,463
Juliano, L. M., & Griffiths, R. R. (2004) · Psychopharmacology · doi:10.1007/s00213-004-2000-x · Cited by 613
“The magnitude of this effect is positively correlated with daily caffeine dose before abstinence (Mathew and Wilson 1985; Field et al. 2003).”
Are we dependent upon coffee and caffeine? A review on human and animal data
Nehlig, A. (1999) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(98)00050-5 · Cited by 453
“This recent study confirms several previous ones that suggested that increased blood volume may be involved in caffeine withdrawal headaches [48] [94] [133] [194].”
ResultCaffeine physical dependence: a review of human and laboratory animal studies
Griffiths, R. R., & Woodson, P. P. (1988) · Psychopharmacology · doi:10.1007/bf00212836 · Cited by 276
The effect of daily caffeine use on cerebral blood flow: How much caffeine can we tolerate?
Addicott, M. A., Yang, L. L., Peiffer, A. M., Burnett, L. R., Burdette, J. H., Chen, M. Y., Hayasaka, S., Kraft, R. A., Maldjian, J. A., & Laurienti, P. J. (2009) · Human Brain Mapping · doi:10.1002/hbm.20732 · Cited by 210
“…anywhere from 8 to 24 hours before the experiment and have reported decreases in CBF between 10% to 30% using positron emission tomography [Cameron et al., 1990], 133Xenon inhalation [Mathew and Wilson, 1985], and pulsed arterial spin labeling [Bendlin et al., 2007; Mulderink et al., 2002].”
BackgroundMethodSubstance abuse and cerebral blood flow
Mathew, R. J., & Wilson, W. H. (1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.3.292 · Cited by 147
Self-citationShould caffeine abuse, dependence, or withdrawal be added to DSM-IV and ICD-10?
Hughes, J. R., Oliveto, A. H., Helzer, J. E., Higgins, S. T., & Bickel, W. K. (1992) · American Journal of Psychiatry · doi:10.1176/ajp.149.1.33 · Cited by 148
Effects of frequent marijuana use on memory-related regional cerebral blood flow
Block, R. I., OʼLeary, D. S., Hichwa, R. D., Augustinack, J. C., Ponto, L. L. B., Ghoneim, M. M., Arndt, S. V., Hurtig, R. R., Watkins, G. L., Hall, J. A., et al. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00771-7 · Cited by 143
“…Warburton, 1995) and cerebral blood flow (Cameron et al., 1990; Ghatan et al., 1998), and produce abstinence effects, including some effects on task performance (James, 1998; Sommese and Patterson, 1995), and at least for caffeine, some effects on cerebral blood flow (Mathew and Wilson, 1985).”
BackgroundDietary Caffeine Consumption Modulates fMRI Measures
Laurienti, P. J., Field, A. S., Burdette, J. H., Maldjian, J. A., Yen, Y.-F., & Moody, D. M. (2002) · NeuroImage · doi:10.1006/nimg.2002.1237 · Cited by 136
“…fact, recent studies have demonstrated that chronic use and withdrawal modulate the stimulant effects of caffeine, associated electroencephalography changes, and resting cerebral perfusion (Field et al., 2002; Jones et al., 2000; Mathew et al., 1983; Mathew and Wilson, 1985; Swerdlow et al., 2000).”
BackgroundField, A. S., Laurienti, P. J., Yen, Y.-F., Burdette, J. H., & Moody, D. M. (2003) · Radiology · doi:10.1148/radiol.2271012173 · Cited by 115
The analgesic effects of caffeine in headache
Ward, N., Whitney, C. W., Avery, D., & Dünner, D. L. (1991) · Pain · doi:10.1016/0304-3959(91)90129-l · Cited by 110
Martin, V. T., & Vij, B. (2016) · Headache The Journal of Head and Face Pain · doi:10.1111/head.12952 · Cited by 99
Sigmon, S. C., Herning, R. I., BETTER, W. E., Cadet, J. L., & Griffiths, R. R. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1489-4 · Cited by 85
“These physiological effects of caffeine withdrawal are consistent with those observed in prior studies (Couturier et al. 1997; Field et al. 2003; Jones et al. 2000; Lader et al. 1996; Mathew and Wilson 1985; Reeves et al. 1995) and extend those findings using a well-controlled experimental design.”
InfluentialHuman Brain Metabolic Response to Caffeine and the Effects of Tolerance
Dager, S. R., Layton, M. E., Strauss, W. L., Richards, T. L., Heide, A. C., Friedman, S. D., Artru, A. A., Hayes, C. E., & Posse, S. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.2.229 · Cited by 77
Sutherland, G. R., Peeling, J., Lesiuk, H. J., Brownstone, R. M., Rydzy, M., Saunders, J. K., & Geiger, J. D. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90157-j · Cited by 78
Kennedy, D. O., & Haskell, C. F. (2011) · Biological Psychology · doi:10.1016/j.biopsycho.2010.12.010 · Cited by 73
Determinants of resting regional cerebral blood flow in normal subjects
Mathew, R. J., Wilson, W. H., & Tant, S. R. (1986) · Biological Psychiatry · doi:10.1016/0006-3223(86)90264-7 · Cited by 71
Self-citationJones, H. E., Herning, R. I., Cadet, J. L., & Griffiths, R. R. (2000) · Psychopharmacology · doi:10.1007/s002130050005 · Cited by 64
“More specifically, the generality of this finding is enhanced by previous studies which measured cerebral blood flow in various brain regions with PET (Cameron et al. 1990) and 133 xenon (Matthew et al. 1983; Matthew and Wilson 1985 ), used both normal (Matthew et al. 1983; Matthew and Wilson 1985; Cameron et al. 1990…”
BackgroundResultInfluentialHypnic headache: A review of clinical features, therapeutic options and outcomes
Liang, J.-F., & Wang, S. (2014) · Cephalalgia · doi:10.1177/0333102414537914 · Cited by 61
“Pharmacologically, caffeine reduces cortical hyperexcitability by regulating the adenosine receptor and is a significant cerebral vasodilator (65,66).”
BackgroundBrain imaging and the effects of caffeine and nicotine
Dager, S., & Friedman, S. (2000) · Annals medicus · doi:10.3109/07853890009002029 · Cited by 53
Central and peripheral effects of sustained caffeine use: tolerance is incomplete
Watson, J., Deary, I., & Kerr, D. (2002) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.2002.01681.x · Cited by 47
Griffiths, R. R., & Mumford, G. K. (1996) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-60963-3_9 · Cited by 49
Retro-Gasserian Glycerol Injection in the Treatment of Chronic Cluster Headache
Ekbom, K., Lindgren, L., Nilsson, B., et al. (1987) · Cephalalgia · doi:10.1046/j.1468-2982.1987.0701021.x · Cited by 45
Effect of Caffeine on Cerebral Blood Flow Response to Somatosensory Stimulation
Meno, J. R., Nguyen, T.-S. K., Jensen, E. M., West, G. A., Groysman, L. I., Kung, D. K., Ngai, A. C., Britz, G. W., & Winn, H. R. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600075 · Cited by 40
“The effects of caffeine on resting levels of CBF have been reported in a number of previous studies (Field et al, 2003; Mathew and Wilson, 1985; Mulderink et al, 2002).”
BackgroundMethodResultBehavioral dependence on caffeine and phencyclidine in rhesus monkeys: Interactive effects
Carroll, M. E., Hagen, E. W., Asencio, M., & Brauer, L. H. (1988) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(88)90406-6 · Cited by 32
Effects of caffeine on cognitive and autonomic measures in heavy and light caffeine consumers
Lyvers, M., Brooks, J., & Matica, D. (2004) · Australian Journal of Psychology · doi:10.1080/00049530410001688119 · Cited by 30
“Aspinall, 1997). The latter include cerebral vasoconstriction ( Mathew & Wilson, 1985 ), decreases in peripheral skin temperature (Bruce, Scott, Lader, & Marks, 1986; Quinlan et al., 1997), and increases in systolic blood pressure (Cameron, Modell, &”
BackgroundBehavioral and cerebrovascular effects of caffeine in patients with anxiety disorders
Mathew, R. J., & Wilson, W. H. (1990) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1990.tb01348.x · Cited by 30
Self-citationDrug-Induced Headache — Does a Critical Dosage Exist?
Scholz, E., Diener, H., & Geiselhart, S. (1988) · Advances in applied neurological sciences · doi:10.1007/978-3-642-73327-7_6 · Cited by 27
Dietary Patterns and Migraine: Insights and Impact
Tu, Y., Chang, C., Yang, C., Tsai, I., Chou, Y.-C., & Yang, C.-P. (2025) · Nutrients · doi:10.3390/nu17040669 · Cited by 25
“Regarding caffeine withdrawal, the underlying mechanism may be vascular, as abstinence from caffeine has been shown to increase cerebral blood flow velocities [62,63].”
Time to Recover From Daily Caffeine Intake
Lin, Y.-S., Weibel, J., Landolt, H., Santini, F., Garbazza, C., Kistler, J., Rehm, S., Rentsch, K., Borgwardt, S., Cajochen, C., et al. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2021.787225 · Cited by 27
“In the current analyses, we corroborated the withdrawal-induced vasodilation by the elevated cerebral blood flow in the withdrawal condition (37-42).”
Regional Cerebral Blood Flow Changes Associated with Amyl Nitrite Inhalation
Mathew, R. J., Wilson, W. H., & Tant, S. R. (1989) · British Journal of Addiction · doi:10.1111/j.1360-0443.1989.tb03462.x · Cited by 23
Self-citationResponses to hypercarbia induced by acetazolamide in panic disorder patients
Mathew, R. J., Wilson, W. H., & Tant, S. (1989) · American Journal of Psychiatry · doi:10.1176/ajp.146.8.996 · Cited by 21
Self-citationIndomethacin/Prochlorperazine/Caffeine
Hoy, S. M., & Scott, L. J. (2011) · CNS Drugs · doi:10.2165/11206740-000000000-00000 · Cited by 17
Postdural puncture headache in obstetrics
Flood, P. D. (2002) · Seminars in Perinatology · doi:10.1053/sper.2002.32205 · Cited by 16
Physiology and Pharmacology of Cerebral Blood Flow and Metabolism
Prough, D. S., & Rogers, A. T. (1989) · Critical Care Clinics · doi:10.1016/s0749-0704(18)30403-2 · Cited by 15
Ferrari, A., SAVINO, G., Gallesi, D., et al. (2006) · Pharmacological Research · doi:10.1016/j.phrs.2006.03.022 · Cited by 13
The Effects of Caffeine on the Brain: A Review
Hammond, D. C. (2003) · Journal of Neurotherapy · doi:10.1300/j184v07n02_07 · Cited by 12
Reeves, R. R., Struve, F. A., & Patrick, G. (2002) · Clinical Electroencephalography · doi:10.1177/155005940203300409 · Cited by 12
Obermann, M., & Holle, D. (2010) · Expert Review of Neurotherapeutics · doi:10.1586/ern.10.112 · Cited by 11
Caffeinated Beverages, Behavior, and Brain Structure
Onaolapo, O. J., & Onaolapo, A. Y. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815864-7.00005-2 · Cited by 14
Dependence upon Coffee and Caffeine: An Update
Nehlig, A. (2004) · CRC Press eBooks · doi:10.1201/9780203618851-16 · Cited by 9
Ghelardini, C., Galeotti, N., Vivoli, E., et al. (2009) · The Journal of Headache and Pain · doi:10.1007/s10194-009-0151-1 · Cited by 8
“cholinergic analgesic effect [15], its ability to abolish hyperalgesia [6] and a vasoconstrictive activity [16].”
BackgroundDependence upon Coffee and Caffeine
Nehlig, A. (2004) · Nutrition, brain, and behavior./Nutrition, brain and behavior · doi:10.1201/9780203618851.ch9 · Cited by 7
Addicott, M. A., Peiffer, A. M., & Laurienti, P. J. (2012) · Journal of Caffeine Research · doi:10.1089/jcr.2011.0027 · Cited by 5
Substance Use and Addictive Disorders: Caffeine
Meredith, S. E., & Griffiths, R. R. (2015) · Wiley eBooks · doi:10.1002/9781118753378.ch73 · Cited by 3
Unconventional treatment methods in Turkish migraine sufferers
Selekler, M., & Komsuoğlu, S. Ş. (2004) · The Journal of Headache and Pain · doi:10.1007/s10194-004-0101-2 · Cited by 2
“A wide variety of physiological changes have been reported following caffeine administration, some of which are known to manifest tolerance development [14].”
BackgroundLin, Y.-S., Weibel, J., Landolt, H., Santini, F., Slawik, H. C., Borgwardt, S., Cajochen, C., & Reichert, C. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.19.440520 · Cited by 2
“…difficulty in concentrating, flu-like symptoms, and elevated neurovascular dilation (Couturier, Laman, van Duijn, & van Duijn, 1997; Ferre et al., 2008; James, 1998; Juliano & Griffiths, 2004; Mathew & Wilson, 1985; Nikodijevic, Jacobson, & Daly, 1993; Sigmon et al., 2009; Weibel et al., 2020).”
Caffeine and headache: relationship with the effects of caffeine on cerebral blood flow.
Nehlig, A. (2004) · Cited by 1
LADER, M. H. (1999) · CRC Press eBooks · doi:10.1201/9781439822470.ch8 · Cited by 1
Time to recover from daily caffeine intakePreprint
Lin, Y.-S., Weibel, J., Landolt, H., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.01.450708 · Cited by 1
Ferrari, A., Pinetti, D., Gallesi, D., et al. (2013) · American journal of pharmacological sciences · doi:10.12691/ajps-1-5-1
“In addition, caffeine contained in the IPC combination can increase the antimigraine effect of indomethacin, potentiating vasoconstriction but, at the same time, it may contribute to the risk of inducing headache as a symptom of toxicity and withdrawal [25].”
BackgroundThe association of anxiety, depression, and headache with caffeine use
Warburton, D. M. (1999) · CRC Press eBooks · doi:10.1201/9781439822470.ch10
Cerebral energy metabolism and blood flow
Nehlig, A. (1999) · CRC Press eBooks · doi:10.1201/9781439822470.ch3
Nehlig, A. (2004) · Nutrition, brain, and behavior./Nutrition, brain and behavior · doi:10.1201/9780203618851.ch12
Metadata
- Authors
- Mathew, R. J., & Wilson, W. H.
- Affiliations
- Vanderbilt University (US)
- Venue
- Headache: The Journal of Head and Face Pain
- Publisher
- Wiley
- Published
- 1985-09
- Volume
- 25
- Issue
- 6
- Pages
- 305-309
- ISSN
- 0017-8748 (ISSN-L)
- 1526-4610
- OpenAlex
- W2049908803
- Cited by
- 55
- References
- 0
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Headache The Journal of Head and Face Pain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH 36117-01A1)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Coffee research and impacts
- Health Sciences › Medicine › Clinical Neurology › Migraine and Headache Studies
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- caffeine, caffeine withdrawal, regional cerebral blood flow, caffeine abstinence, caffeine dependence
- MeSH terms
- Adult, Caffeine, Cerebrovascular Circulation, Female, Humans, Male, Middle Aged, Substance Withdrawal Syndrome
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