After sudden cessation of caffeine, many people will experience a range of un- pleasant signs and symptoms, commonly referred to as caffeine withdrawal (Box 3–2). Up to 50% of those with abrupt cessation of caffeine may experience caffeine withdrawal. These signs and symptoms typically emerge 12–24 hours after terminating caffeine intake, although onset as late as 36 hours has been documented. The duration of withdrawal for most people is roughly 1 day, last- ing up to 1 week in some. Given the relatively short half-life of caffeine, most chronic users of caffeine actually experience daily morning withdrawal that is relieved by their morning coffee or tea. The most commonly described with- drawal symptom is headache, often gradual in onset and diffuse in location, usually mild but sometimes throbbing and severe. Other common features in- clude fatigue, drowsiness, psychomotor retardation, deceased concentration, irritability, anxiety, and decreased mood. Some people even experience flu-like symptoms (Heatherley 2011).
Box 3–2. DSM-5 Criteria for Caffeine Withdrawal 292.0 (F15.93)
A. Prolonged daily use of caffeine.
B. Abrupt cessation of or reduction in caffeine use, followed within 24 hours by three (or more) of the following signs or symptoms:
1. Headache.
2. Marked fatigue or drowsiness.
3. Dysphoric mood, depressed mood, or irritability. 4. Difficulty concentrating.
5. Flu-like symptoms (nausea, vomiting, or muscle pain/stiffness). C. The signs or symptoms in Criterion B cause clinically significant distress
or impairment in social, occupational, or other important areas of func- tioning.
D. The signs or symptoms are not associated with the physiological effects of another medical condition (e.g., migraine, viral illness) and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
Source. Reprinted from the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Washington, DC, American Psychiatric Association, 2013. Used with permission. Copyright © 2013 American Psychiatric Association.
Treatment
The first step in treating caffeine overuse is for patients to learn about the po- tential consequences of use and to understand the interaction between their use and outcomes. One way to do this is by doing a functional analysis. A functional analysis is an assessment of the chain of events that precede and follow the use of a substance. Helping caffeine users to understand the antecedents, or the po- tential triggers, and the consequences of their use can be an integral part of changing their use patterns.
To facilitate abstinence while reducing the chance of withdrawal symptoms, it is recommended that caffeine intake be gradually reduced over the course of 1 week. Not everyone will experience withdrawal symptoms. This is somewhat dependent on length of use and amount, and on polymorphisms of the adenosine receptor A2A gene. This is consistent with the reduction in caffeine intake by in- dividuals homozygous for an adenosine receptor A2A gene variant. For many caffeine users, there is a lack of withdrawal symptoms on abrupt discontinuation. For most of those who do have withdrawal symptoms, the discomfort tends to be mild. Therefore, unplanned, abrupt discontinuation (e.g., from an emergency procedure) is not typically treated with caffeine replacement as are many other substances with a withdrawal profile.
Although there are treatment facilities that report helping patients detoxify from caffeine, they are rarely used (Heatherley 2011).
Key Points
• Many people are unaware of the health risks of caffeine and the wide range of users’ susceptibility to its effects.
• There are a number of cytochrome P450 interactions that can affect the rate of metabolism and the effects of caffeine. • There is a trend toward increased caffeine consumption, primar-
ily through the use of energy drinks.
• There are potentially dangerous interactions between caffeine and alcohol, which is becoming an increasingly popular combi- nation.
References
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disor- ders, 5th Edition. Washington, DC, American Psychiatric Association, 2013 Heatherley SV: Caffeine withdrawal, sleepiness, and driving performance: what does the
research really tell us? Nutr Neurosci 14:89–95, 2011
Howland J, Rohsenow DJ: Risk of energy drinks mixed with alcohol. JAMA 309:245– 246, 2013
Reissig CJ, Strain EC, Griffiths RR: Caffeinated energy drinks: a growing problem. Drug Alcohol Depend 99:1–10, 2009
Sepkowitz K: Energy drinks and caffeine: related adverse effects. JAMA 309:243–244, 2013
Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality: The DAWN Report: Update on Emergency Depart- ment Visits Involving Energy Drinks: A Continuing Public Health Concern. Rock- ville, MD, Substance Abuse and Mental Health Services Administration, 2013
Questions
3.1 The most likely users of energy drinks are
A. Males 18–24 years old. B. Females 10–24 years old. C. Males 35–50 years old. D. Females 35–50 years old.
Most consumers of energy drinks are men between the ages of 18 and 24. However, the use of energy drinks in older adults, regardless of gender, is increasing.
3.2 Cigarette smoking affects caffeine metabolism by being a potent _______ of the cytochrome P450 1A2 enzyme.
A. Substrate. B. Inhibitor. C. Inducer.
D. None of the above.
The correct answer is C.
Cigarette smoking leads to an increase in cytochrome P450 1A2 enzyme production. This results in a faster clearance of caffeine through an in- crease in its metabolism. Abrupt cessation of cigarette smoking will lead to a brisk rebound in caffeine blood levels.
3.3 The effects of caffeine are related to
A. Genetics. B. Amount of use.
C. Interactions of other substances with the CYP450 system. D. All of the above.
The correct answer is D.
The effects of caffeine are related to a complex array of factors, including genes, amount of use, and rate of metabolism by the cytochrome P450 1A2 enzyme system.
3.4 The combination of caffeine and alcohol
A. Decreases the rate of alcohol-related accidents by reducing sedation. B. Increases the rate of sexual assaults.
C. Is illegal in most states. D. Is decreasing in popularity.
The correct answer is B.
It has been shown that people who mix caffeine with alcohol are at in- creased risk for being exposed to or propagating a sexual assault.
3.5 The most commonly experienced symptom of caffeine withdrawal is
A. Nausea. B. Tremor. C. Tachycardia. D. Headache.
The correct answer is D.
Headache is the most common side effect associated with caffeine with- drawal.