Caffeine Withdrawal Headaches: Should you be worried?

Caffeine is probably one of the world's best-recognised chemicals. It is contained in many foods and beverages, including those taken habitually for their purported beneficial effects. Caffeine is not classed as a drug, although it is pharmaceutically active. In other words, it can generate effects on the central nervous system and some autonomic processes when ingested. The more well-known of these are increased alertness and decreased sleepiness, as well as diuresis (or acute increased water loss through excretion).

Caffeine is a xanthine and is similar in structure to the purines adenine and guanine, which are important components of DNA; an alternative name for caffeine is guaranine. This allows it to bind to the receptors for adenosine (an adenine derivative that plays important roles in the body). It does not activate the receptor, but simply occupies it and prevents adenosine from binding to it instead. Adenosine receptors are found in many areas of the body, including parts of the brain that increase the urge to sleep in response to increasing levels of adenosine activity during the day. 

Therefore, caffeine acts to reduce drowsiness or sleepiness by preventing this. However, this is temporary and may vary greatly from person to person. 

This property enables caffeine to improve performance during sleep deprivation, and may also treat sleep inertia, in which people feel sluggish, confused and discomfited on waking.

Caffeine may also potentiate the effects of other drugs, most notably analgesics, or painkillers used for common conditions such as headache. This is thought to be related to both adenosine receptor blockage, and to its ability to increase the acidity of the stomach.

Sources of caffeine

• Coffee; a beverage made by steeping the grounds of roast Coffea arabica beans in water. This may deliver between 80 and 125mg caffeine per cup, depending on the type of coffee preparation and quality of the beans used.
• Tea: another beverage made by steeping the leaves of tea plants in a similar way
• Chocolate (particularly dark chocolate)
• Soft drinks
• Energy drinks; a type of soft drink with often greatly increased concentrations of caffeine
• Many formulations of oral painkillers (including aspirin, paracetamol and ibuprofen) may also contain caffeine
• Caffeine pills

Caffeine is regarded as safe for ingestion, mainly due to its close resemblance to purines, which are normally present in large concentrations throughout the body. Despite this, the sudden absence of regular caffeine intake may result in adverse effects and discomfort. This is known as caffeine withdrawal, a form of physiological dependence. Caffeine withdrawal is seen as a considerable problem by some researchers.

Caffeine Withdrawal

Caffeine withdrawal is a range of unpleasant symptoms resulting from the sudden discontinuation of regular caffeine intake. Caffeine withdrawal symptoms typically arise in the first 12 to 24 hours of discontinuing or delaying normal intake. These may 'peak' between the 20th and 51st hour following discontinuation. Symptoms may include:

• Anxiety
• Depressive symptoms
• Increased drowsiness
• Increased lethargy
• Intense desire for coffee
• Irritability
• Reduced concentration
• Impaired cognition
• Reduced occupational or professional performance
• Muscular pain or stiffness
• Nausea and/or vomiting
• Headache

Pain, that may be moderate to severe, may have an onset at around 18 hours after cessation. Caffeine withdrawal headaches may be felt as intense pressure in the front of the skull, and may then spread to other areas. Approximately 50% of regular caffeine users experience headache during withdrawal, and 13% will find the effects of withdrawal to be significantly debilitating.

The risk of experiencing withdrawal symptoms is thought to increase with the amount of caffeine ingested per day. However, those whose intake is low to moderate (about 200mg per day) are also at risk of withdrawal.

Caffeine withdrawal may be treated with a small dose (about 100mg) of caffeine. Alternatively, a patient could 'detoxify' or wait for the symptoms to abate, which may take up to nine days. Non-caffeine treatments may include conventional painkillers such as paracetamol. However, many commercially-produced over-the-counter analgesics contain caffeine, as mentioned above. If an individual wishes to abstain from caffeine during or as a result of withdrawal, this should be kept in mind.

Caffeine Withdrawal Headache - Health Implications

Headache as a result of caffeine withdrawal is a relatively common occurrence, with an approximately 10% chance of resulting in significant (albeit temporary) discomfort and functional impairment, as outlined above. However, they are not often an indication of severe illness. An exception is the purported role of this type of headache (termed a medication overuse headache) in the development of migraine headaches. Some research has concluded that the increased intake of drugs and caffeine is a risk factor for chronic migraine.

Other Health Effects of Caffeine

Caffeine is not historically linked to addiction. However, a recent study demonstrated the ability of caffeine to influence levels of the neurotransmitter dopamine in the brain by inhibiting the regulation of this by adenosine. Changes in dopamine are associated with other drugs known to cause addiction, such as cocaine.

Some other studies found increases in caffeine 'cravings' among people with a regular intake of caffeine. This indicates a greater tendency toward dependence on caffeine than was previously thought.

Tolerance to caffeine may also be an issue, although this may vary from person to person. Despite this, caffeine abuse is not seen as a major societal problem.

Caffeine in high doses may also be associated with the increased severity of anxiety disorders. This may indicate a relationship between adenosine receptor blocking and psychiatric disorders, although this has not yet been confirmed.

Regular caffeine intake is also associated with positive health benefits. Caffeine is associated with reduced risks of liver damage (or cirrhosis) and some types of liver cancer. It may also be associated with reduced risks of depression in women. Moderate and high intake consumption of coffee may also reduce the risk of type II diabetes. A longitudinal study including over 8000 participants found that caffeine was associated with a significantly reduced incidence of Parkinson's disease. Caffeine is also indicated in the preventative treatment of hypnic headache, a type of headache that has an onset as a result of sleep.

References

1. Newman RA, Kamimori GH, Wesensten NJ, Picchioni D, Balkin TJ. Caffeine gum minimizes sleep inertia. Perceptual and motor skills. 2013;116(1):280-293.
2. Petersen KU. [Caffeine in analgesics--myth or medicine?]. MMW Fortschr Med. 2013;155 Suppl 4:109-114.
3. Yoovathaworn KC, Sriwatanakul K, Thithapandha A. Influence of caffeine on aspirin pharmacokinetics. European journal of drug metabolism and pharmacokinetics. 1986;11(1):71-76.
4. Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology. 2004;176(1):1-29.
5. Ferre S. An update on the mechanisms of the psychostimulant effects of caffeine. Journal of neurochemistry. 2008;105(4):1067-1079.
6. Greden JF, Victor BS, Fontaine P, Lubetsky M. Caffeine-withdrawal headache: a clinical profile. Psychosomatics. 1980;21(5):411-413, 417-418.
7. Silverman K, Evans SM, Strain EC, Griffiths RR. Withdrawal syndrome after the double-blind cessation of caffeine consumption. The New England journal of medicine. 1992;327(16):1109-1114.
8. Carod-Artal FJ. Tackling chronic migraine: current perspectives. J Pain Res. 2014;7:185-194.
9. Meredith SE, Juliano LM, Hughes JR, Griffiths RR. Caffeine Use Disorder: A Comprehensive Review and Research Agenda. Journal of Caffeine Research. 2013;3(3):114-130.
10. Addicott MA. Caffeine Use Disorder: A Review of the Evidence and Future Implications. Current addiction reports. 2014;1(3):186-192.
11. Cornelis MC, Monda KL, Yu K, et al. Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption. PLoS genetics. 2011;7(4):e1002033.
12. Yamada K, Kobayashi M, Kanda T. Involvement of adenosine A2A receptors in depression and anxiety. Int Rev Neurobiol. 2014;119:373-393.
13. Inoue M, Yoshimi I, Sobue T, Tsugane S, Group JS. Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a prospective study in Japan. J Natl Cancer Inst. 2005;97(4):293-300.
14. van Dam RM, Hu FB. Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA. 2005;294(1):97-104.
15. Ross GW, Abbott RD, Petrovitch H, et al. Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA. 2000;283(20):2674-2679.
16. Liang J-F, Wang S-J. Hypnic headache: a review of clinical features, therapeutic options and outcomes. Cephalalgia. 2014;34(10):795-805.