The World of Caffeine (55 page)

There are few studies of the effects of caffeine on human emotional states other than anxiety and depression. However, some researchers have hypothesized that caffeine may operate to decrease aggression, arguing that an increase in benzodiazepine activity increases aggression, and, as we have seen, caffeine inhibits benzodiazepine activity. Studies in 1983 and 1984 by D.R.Cherek
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examining the effects of caffeine administration on aggressive behavior seem to confirm these findings in humans. Mindful of the aggressive response normally elicited when someone has money taken from him, Cherek designed an experiment in which subjects were promised certain immediate rewards for their performance. He then pretended to renege on his promises, giving the participants, who had received either caffeine tablets, coffee, decaffeinated coffee, or a placebo, the impression that they had been “ripped off.” He found that those who had ingested either coffee or caffeine were more tolerant of being cheated. However, the specter of dubiety that haunts many other caffeinerelated inquiries appears in connection with the issue of mood effects as well. For, in contrast with Cherek’s work, the 1987 study by Roache and Griffiths mentioned earlier, in which subjects consumed between 200 and 600 mg of caffeine, produced small increases in scores on the Profile of Mood States Questionnaire (POMS) for hostility and anger, while also demonstrating an increase in friendliness.
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J.A.Brillat-Savarin, perhaps the most celebrated chef in history, wrote, in
The Physiology of Taste
(1805), “It is beyond doubt that coffee greatly excites the cerebral powers; also any man who drinks it for the first time is bound to be kept from a share of his natural sleep.” In fact, everywhere caffeine-containing beverages have been consumed, people have recognized that, just as they can help you to stay awake, they can also interfere with a good night’s sleep. The most common sleep disturbance associated with caffeine is insomnia, although there is, oddly enough, a complaint called “hypersomnia,” or too much sleep, also sometimes consequent to its use. Among researchers, it is generally accepted that caffeine is a common cause of sleep disturbances. In fact, according to P.B.Dews, a leading caffeine researcher, the disturbance of nighttime sleep is much more pronounced and dose dependent than caffeine’s daytime effects.
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Despite great variation in the amount of sleep that people need, ranging from as few as three to as many as twelve hours, with an average of seven to nine, certain general observations are possible. For example, scientists divide sleep into dreamless sleep and the sleep during which we dream. REM is an acronym for “rapid eye movement,” and dreaming sleep is called REM sleep because during our dreams we follow the action, as it were, by shifting our “gaze” back and forth. Non-REM sleep usually lasts about an hour or more and then shifts to REM sleep for about thirty minutes, in a pattern called the “ultradian rhythm” that is repeated four to six times throughout the night. Non-REM sleep, which itself comprises four states of progressively deeper dreamless sleep, constitutes about 75 percent of our sleep, and is characterized by lowered heart and respiration rates, while REM sleep is marked by deep muscular relaxation accompanied by increased or irregular heart and respiration rates and vivid dreaming.
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At the beginning of the night’s sleep, deeper non-REM sleep is a greater proportion of the ultradian cycle than toward the end of the night’s sleep, during which the proportion of lighter REM sleep increases. Interrupting or interfering with either REM or non-REM sleep causes a sleep deficit that the body seeks to restore over succeeding nights. A mounting sleep deficit can impair concentration, diminish energy and performance during the day, and increase anxiety and depression. Extreme sleep deprivation can cause paranoia and hallucinations. One in three adults regularly suffers from sleep problems, and medications are resorted to as a remedy by millions.

Caffeine’s effects on sleep depend on a variety of factors, such as dosage, tolerance to caffeine, individual sensitivity to caffeine, the time between caffeine ingestion and the attempt to sleep, and the ingestion of other psychoactive substances. There are studies confirming the common experience that acute doses of caffeine in the evening delay falling asleep and result in
poorer sleep quality. For example, a Japanese study showed that it takes four times longer than normal to get to sleep after drinking a strong cup of coffee. But caffeine can do more than interfere with falling asleep: It can also produce alterations in the onset of REM sleep, total sleep time, and certain characteristics of non-REM sleep, such as shortening the deeper phases of nonREM sleep and lengthening the lighter phases. It does not appear that caffeine affects the length of the REM phase of sleep.
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Heavy caffeine users toss and turn more in bed, perhaps because caffeine increases muscle tension and restlessness. Such movements can also cause frequent awakening.
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In addition, people who consume caffeine before bedtime are more easily awakened by sudden noises. Brain-wave studies show that caffeine disturbs sleep during the first three to four hours. A study of subjects over age fifty found sleep was reduced by as much as two hours when caffeine was taken in the evening. Because older people sleep less than younger people anyway, this diminution represents a proportionately greater loss than it would for younger people.
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Just as people vary in the amount of sleep they need, they vary in the effect caffeine has on their sleep. You have almost certainly met people who claim to be able to sleep well after drinking a couple strong cups of coffee immediately before retiring. Even stranger is the fact that some people are not only capable of sleeping well after consuming caffeine but actually sleep too much, experiencing a condition of pathologic sleepiness called “hypersomnia,” as a result of consuming it. As “Pathologic Sleepiness Induced by Caffeine,” a paper published by Quentin R.Regestein in 1989 in the
American Journal of
Medicine,
states:

Another strange effect, which might be called the “reverse placebo” effect, was observed by A.Goldstein in a 1964 study. Participants in his experiment were all given caffeine. Those who knew they had taken the drug were less likely to complain of wakefulness than those who were not informed whether they had taken caffeine or a placebo.
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Perhaps this could also be called the “bravado effect,” whereby people are reluctant to confess a disturbance from what is ordinarily considered a mild agent, such as caffeine. Surveys based on
subjective
responses clearly indicate that how much caffeine people say they use is not related to how much difficulty they say they have sleeping, and insomniacs do not report high caffeine use, defined as three or more cups of coffee a day. In any case, most studies confirm that the closer to bedtime you consume caffeine, the more likely it is to interfere with sleep. However, as we have observed in our discussion of metabolic variation, some people metabolize caffeine much more slowly than others, and their sleep may be disturbed even by caffeine consumed twelve hours or more earlier.

Other studies of delayed sleep onset and poorer sleep quality, as evaluated on
objective
criteria such as EEG measurements, confirmed the well-recognized large variation among subjects in terms of caffeine’s effect on sleep (intersubject variation) and also documented a similar large variation in the effect on the same subject on different nights (intrasubject variation). These studies have also demonstrated that sleep disturbances due to caffeine are more likely to occur in people who are not regular caffeine consumers and that the regular use of caffeine and a concomitant caffeine tolerance tends to diminish the disruptive effect of caffeine on sleep.

Overall, the leading research projects based on objective criteria demonstrate that caffeine intake near bedtime increases tossing and turning, reduces deep sleep and increases light sleep, has no effect on REM sleep, increases the time it takes to fall asleep up to threefold, decreases total sleep time by nearly two hours, and increases spontaneous awakenings. People who have not consumed caffeine before bedtime will fall back to sleep after being awakened early in the night more slowly than they will after being awakened later on. However, caffeine consumed shortly before bedtime reverses this pattern, creating the shortest delay in falling back to sleep in the first part of the night. Because the average plasma half-life for caffeine, a measure of how long it remains in the bloodstream, is between three and seven hours, a large enough dose would tend to sustain this effect throughout half the night. Although differing rates at which caffeine is metabolized by different people are generally thought to be the basis of the differences of effects among them, another school of thought attributes the variations in caffeine’s effect on sleep among individuals to differences in neural response sensitivity.
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Progress in understanding drug dependence has been impeded by a host of nonscientific moral, emotional, and legal factors. Fear of lethal drugs of abuse, such as heroin and cocaine, has clouded what might otherwise have been a neutral and relatively straightforward evaluation of the nature and extent of the habit-forming properties of less dangerous agencies, such as marijuana and caffeine, engendering confusion and doing little to encourage much-needed studies.

The word “dependence” is used in scientific literature in at least two distinct ways. “Physical dependence” is defined by the occurrence of a withdrawal syndrome after cessation of the use of a substance. Opium, cigarettes, and coffee each contain a psychoactive drug producing physical dependence: morphine, nicotine, and caffeine, respectively. “Clinical dependence syndrome” usually includes physical dependence, but also involves a pattern of pathologic behavior. Drugs that can support a clinical dependence syndrome are usually considered drugs of abuse. A heroin addict, whose behavior is deleteriously conditioned by his need to acquire the drug, exhibits clinical dependence syndrome. In contrast, a cancer patient under extended treatment with opioids will demonstrate physical dependence, but would probably not display any other symptoms of clinical dependence.

Caffeine unquestionably supports a physical dependence, as proved by the withdrawal symptoms associated with its abrupt discontinuation. It also has several additional characteristics in common with drugs that support a clinical dependence syndrome. These characteristics include both caffeine’s ability to improve people’s moods, self-confidence, and energy and what researchers call its ability to act as a reinforcer, or what in laymen’s terms might be phrased as “the more you get, the more you want” factor. Yet despite the reasonableness of the hypothesis and considerable anecdotal evidence, it has been demonstrated only recently that there actually are users whose pattern of caffeine consumption merits a diagnosis of clinical dependence syndrome. In the American Psychiatric Association’s
DSM-IV,
caffeine was the only psychoactive substance listed as supporting a physical dependence but not a clinical dependence syndrome. If research in this area continues, caffeine will probably lose this distinction by the time of the publication of the
DSM-V
.

As early as 1893, a researcher, N.Bridge, reported on a series of patients presenting a variety of symptoms he attributed to the use of coffee or tea, concluding that eliminating caffeine from their diets could be beneficial.
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However, he warned that patients who terminated their caffeine use abruptly were at risk for developing a severe headache. In consequence he recommended a regimen similar to the one favored by physicians today, reducing coffee consumption gradually over a week or more.

Headaches associated with the abrupt cessation of caffeine use have been experienced by millions in their daily lives and constitute the most typical feature of caffeine withdrawal and the most immediate evidence that caffeine supports a physical dependence. Other common symptoms of caffeine withdrawal, some of which the reader may have experienced when unable to enjoy his accustomed morning brew, can include:

• Sleepiness: drowsiness, yawning
  
• Work difficulty: impaired concentration, lassitude, decreased motivation for work
  
• Irritability: decreased contentedness, well-being, and self-confidence
  
• Decreased sociability: reduced friendliness and talkativeness
  
• Flulike symptoms: muscle aches and stiffness, hot or cold spells, nausea or vomiting, and blurred vision
  

Additional reported symptoms are increased depression or anxiety or impaired psychomotor performance.

In a detailed, carefully controlled study in 1986, Roland Griffiths provided a more detailed schedule of caffeine withdrawal symptoms than had been available previously. He found that caffeine withdrawal generally begins within twelve to twenty-four hours after discontinuing caffeine use. It generally peaks within twenty-four to fortyeight hours, and it lasts from about two days to a week.
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As with many of the manifestations of caffeine use, there is considerable variability both between people and within the same person in the effects, duration, and severity of caffeine withdrawal.

The single best estimate of the incidence of caffeine withdrawal symptoms in a clinical setting was provided in a 1992 study
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of more than sixty normal adults with low to moderate daily caffeine consumption, an average of 235 mg a day, or the equivalent of about two cups of coffee. This was a double-blind study, that is, one in which neither the researcher nor the subject knows who is receiving caffeine and, if so, in what quantities. More than 50 percent of the participants who did not receive caffeine had moderate to severe headaches, about 10 percent had symptoms associated with anxiety and depression, and about another 10 percent had significantly high ratings of fatigue. Nearly 15 percent used analgesics for aches and pains occasioned by withdrawal.

What is it about the cessation or relative decrease in the intake of caffeine that generates the range of physical and psychological problems listed above? Caffeine withdrawal is probably caused by the cessation of adenosine antagonism, which is caffeine’s chief pharmacological mechanism of action. When caffeine use ceases, caffeine’s supression of adenosine ceases, and it is natural that the abstainer should experience sluggishness, torpor, difficulty in concentrating, and depression. In addition, the prior use of caffeine may have resulted in a compensatory increase in the number of adenosine receptor sites, intended by the body to help restore the level of adenosine to that which existed before regular caffeine use.
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Specifically, caffeine withdrawal symptoms may be partially explained by the decrease in central nervous system activity and the increase in cerebral blood flow associated with increased adenosine activity. The results of an EEG study which demonstrated increased alpha and beta voltage in the frontal-central cortex during caffeine withdrawal has been interpreted as being consistent with the hypothesis that caffeine withdrawal may be due to cerebral blood flow changes.
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The most common and notorious feature of caffeine withdrawal is the headache, which, consistently with the above analysis, has been described as a feeling of cerebral fullness. Typically it is a generalized throbbing headache that can, in extreme cases, be accompanied by flulike symptoms such as nausea and vomiting. The caffeine withdrawal headache is worsened with physical exercise and, not surprisingly, is relieved by caffeine. The withdrawal headaches usually abate within two to four days, although some subjects continue reporting sporadic headaches for ten days or more after cessation of caffeine use. It should be noted that several reports have concluded that sudden extreme increases in caffeine or coffee consumption can also produce headaches.

The caffeine withdrawal headache has frequently been observed in a hospital setting. One registered nurse at a hospital reports what turns out a common pre- and post-operative observation of caffeine withdrawal: “When I worked in an ambulatory surgery setting, many patients who were NPO [not to eat or drink anything] and therefore [had gone] without their usual cup of caffeine since the night before would experience quite severe headaches if they were still NPO by 11 A.M. or so. For most routine caffeine users, the
first
thing they said in the recovery area was ‘Can I get some coffee?! I have a headache!’ The phenomenon occurred often enough that even nurses new to the area caught on pretty quickly, and widespread enough for it to be a topic of informal conversation during nationwide nurses’ conventions!”
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Recently some surgical teams have given patients caffeine intravenously to avoid headaches and other withdrawal symptoms during the operation and recovery periods.

This complex of caffeine withdrawal symptoms is compellingly reminiscent of what might be termed the “addict’s flu,” the generalized withdrawal symptoms common to many addictive drugs, notably including heroin and other opiates and barbiturates. The symptoms of withdrawal from these drugs are typically much more severe than those exhibited in the flulike symptoms of caffeine withdrawal, but the pattern of symptoms, including fatigue, aches and pains, irritability, running nose, perspiration, and cravings for the drug, are otherwise identical.

Several studies have found that both the likelihood of caffeine withdrawal and its severity increase as the daily dose attained before cessation is increased. However, it has been shown that caffeine withdrawal can occur after discontinuation of surprisingly low regular doses of caffeine, as little as 100 mg per day, which is the equivalent of about one cup of coffee or two cans of cola.

There is one report of eight infants with suspected caffeine withdrawal born to mothers who had moderate to heavy caffeine consumption during their pregnancies (200–1,800 mg a day). The infants’ symptoms, including irritability, jitteriness, and vomiting, began an average of about twenty hours after birth and then abated completely.
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The possible onset of caffeine withdrawal makes it advantageous for caffeine users to plan ahead as they approach circumstances where it may be necessary or desirable to eliminate caffeine. Because many general medical conditions can
have signs and symptoms that are similar to caffeine withdrawal, it is necessary to systematically exclude other explanations for the symptoms. An adequate differential diagnosis should encompass conditions as diverse as viral illnesses, sinus conditions, migraine or tension headaches, other drug withdrawal states, such as amphetamine or cocaine withdrawal, and idiopathic drug reactions.

Opinions vary among psychologists and psychiatrists about whether caffeine should be branded, along with heroin, cocaine, and nicotine, as a drug of abuse, that is, as an agent supporting a clinical dependence syndrome. The majority opinion, supported in studies by Strain, Griffiths, and others at the Department of Psychiatry and Behavioral Sciences, the Johns Hopkins University School of Medicine, and reported in
JAMA
in 1994,
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provides clinical evidence supporting a caffeine clinical dependence syndrome similar to the dependence syndromes of heroin and cocaine but milder.
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A minority of professionals, citing the modest and transient discomforts of caffeine withdrawal, assert that caffeine has little in common with dangerous psychoactive drugs of abuse and should not be described as supporting a clinical dependence syndrome.
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The best opinion seems to be an amalgam of the two. On the one hand, there is no doubt that caffeine, like cocaine, has all the hallmarks of a drug that supports a clinical dependence syndrome: It produces the subjective effects of euphoria, energy, and self-confidence; it demonstrates a “reinforcing effect,” that is, the capacity of a pharmacological agent to encourage sustained use; and, finally, as we have noted, it supports a physical dependence, including a developed tolerance and withdrawal symptoms on cessation.
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On the other hand, it is clear that caffeine’s subjective effects, reinforcing effects, and withdrawal symptoms are far less pronounced than the recognized drugs of abuse, such as cocaine, dextroamphetamine, or pentobarbital, and therefore, caffeine’s clinical dependence syndrome, if it indeed exists, cannot be uncritically equated with the clinical dependence syndromes of these other drugs.
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Extrapolating from a telephone survey of two hundred Vermont residents conducted by a group of researchers in 1992
¹³
(the only study using standardized psychiatric criteria to evaluate the prevalence of caffeine clinical dependence), and applying the estimate that more than 80 percent of all American adults consume caffeine daily, with an average consumption among users of nearly 300 mg a day, we could venture that, in the United States alone, 75 million people would fit the criteria for moderate caffeine clinical dependence syndrome. The average daily consumption and, therefore, the estimate of the levels of this dependence syndrome in other countries may be considerably higher.

So the question remains: Does caffeine, like cocaine, support compulsive use, that is, an habitual pattern of self-administration persisting despite untoward personal, health, economic, or social consequences and repeated attempts to discontinue taking it? It is very difficult to determine the extent to which the nearly universal use of caffeine, in some surveys reaching 92 to 98 percent of North American adults, is, in one researcher’s words, “due to its centrally mediated stimulus functions, rather than liking the taste of hot coffee, or the fact that drinking coffee is such a socially acceptable behavior.”
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Although anecdotal reports of the regular patterns of consumption engaged in by most caffeine users satisfy the criterion of habitual use, there is little evidence to help us decide whether the strength of the desire to persist in these patterns would satisfy the definition of compulsive behavior. Nevertheless, it remains a credible speculation that a minority of caffeine users consume caffeine compulsively, to the extent that they would find it difficult to reduce or eliminate it from their diet. Whatever the outcome of current studies, it is safe to assert that caffeine dependence, like other drug dependence syndromes, in all likelihood represents the interaction of social and cultural forces, of individual histories and predispositions operating at the same time as a psychoactive substance that produces pleasant mood-altering and reinforcing effects.