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Chapter 50. Coffee and Anxiety
Abstract
This chapter discusses the effects of coffee consumption on anxiety response, taking into account vulnerability factors such as sex and genetics. In light of research concerning the effects of coffee on normal anxiety, and particularly research carried out in our laboratory, current knowledge can be summarized as follows: (1) men appear to be more sensitive to the effects of coffee than women; and (2) coffee can increase alertness in habitual consumers after acute deprivation, but not above the level of that observed in nonconsumers. In addition, we discuss clinical evidence of the varying sensitivity of anxiety disorder patients to the effects of coffee. The caffeine challenge test, a useful biological model of panic attacks, has shown that individuals suffering panic disorder or performance social anxiety disorder are particularly sensitive to the effects of caffeine and may benefit from a reduction in their intake. This greater sensitivity seems to have a genetic basis.
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The objective was to evaluate the effects of a single dose of alcohol, caffeine, and nicotine, alone or in combination, on physiological parameters (systolic and diastolic blood pressure [SBP and DBP] and heart rate [HR]) and state-trait anxiety in healthy young volunteers.
The procedure reproduces the conditions under which the subjects (n=76) usually ingest alcohol (through an alcoholic beverage), caffeine (through a cup of coffee), and nicotine (by smoking a cigarette), separately or in combination, according to their consumption habits of each individual. SBP and DBP, HR, and state anxiety (SA) were registered before (phase 1) and after (phase 2) treatment.
Intake of alcohol or alcohol-nicotine reduced DBP. Comparisons between control and combined treatment (coffee-alcohol-nicotine) groups revealed a decrease in HR in the former group but not in the latter. The coffee consumers alone exhibited a tendency toward an increase in SA, while the control group showed a tendency toward a decrease in this measure. When Phase 1 and Phase 2 were compared, a decrease was observed in SBP (alcohol and coffee-alcohol groups), DBP (alcohol and alcohol-nicotine groups), HR (all groups, except coffee-alcohol and coffee-alcohol-nicotine groups), and SA (coffee-alcohol-nicotine group).
(i) A low dose of alcohol, either alone or in combination with a cigarette, decreases DBP but not SBP; (ii) the polyconsumption of coffee, alcohol, and nicotine blocks the adaptation response (the reduction in HR in control subjects in the second phase); (iii) an increase of SA is observed after consuming coffee, while the opposite occurs in control subjects (a decrease of SA).
Caffeine, a widely consumed adenosine A(1) and A(2A) receptor antagonist, is valued as a psychostimulant, but it is also anxiogenic. An association between a variant within the ADORA2A gene (rs5751876) and caffeine-induced anxiety has been reported for individuals who habitually consume little caffeine. This study investigated whether this single nucleotide polymorphism (SNP) might also affect habitual caffeine intake, and whether habitual intake might moderate the anxiogenic effect of caffeine. Participants were 162 non-/low (NL) and 217 medium/high (MH) caffeine consumers. In a randomized, double-blind, parallel groups design they rated anxiety, alertness, and headache before and after 100 mg caffeine and again after another 150 mg caffeine given 90 min later, or after placebo on both occasions. Caffeine intake was prohibited for 16 h before the first dose of caffeine/placebo. Results showed greater susceptibility to caffeine-induced anxiety, but not lower habitual caffeine intake (indeed coffee intake was higher), in the rs5751876 TT genotype group, and a reduced anxiety response in MH vs NL participants irrespective of genotype. Apart from the almost completely linked ADORA2A SNP rs3761422, no other of eight ADORA2A and seven ADORA1 SNPs studied were found to be clearly associated with effects of caffeine on anxiety, alertness, or headache. Placebo administration in MH participants decreased alertness and increased headache. Caffeine did not increase alertness in NL participants. With frequent consumption, substantial tolerance develops to the anxiogenic effect of caffeine, even in genetically susceptible individuals, but no net benefit for alertness is gained, as caffeine abstinence reduces alertness and consumption merely returns it to baseline.
People with diabetes mellitus are at increased risk of cognitive dysfunction. This review explores the relation between caffeine intake, diabetes, cognition and dementia, focusing on type 2 diabetes (T2DM). Epidemiological studies on caffeine/coffee intake and T2DM risk are reviewed. Next, the impact of T2DM on cognition is addressed. Finally, the potential for caffeine to modulate the risk of cognitive decline in the context of diabetes is explored. The conclusion is that, although epidemiological studies indicate that coffee/caffeine consumption is associated with a decreased risk of T2DM and possibly also with a decreased dementia risk, we can at present not be certain that these associations are causal. For now, recommendations for coffee consumption in individuals with T2DM or pre-diabetic stages are therefore difficult to establish, but it should be acknowledged that caffeine does appear to have several properties that warrant further investigations in this field.
The effects of caffeine on cognition were reviewed based on the large body of literature available on the topic. Caffeine does not usually affect performance in learning and memory tasks, although caffeine may occasionally have facilitatory or inhibitory effects on memory and learning. Caffeine facilitates learning in tasks in which information is presented passively; in tasks in which material is learned intentionally, caffeine has no effect. Caffeine facilitates performance in tasks involving working memory to a limited extent, but hinders performance in tasks that heavily depend on working memory, and caffeine appears to rather improve memory performance under suboptimal alertness conditions. Most studies, however, found improvements in reaction time. The ingestion of caffeine does not seem to affect long-term memory. At low doses, caffeine improves hedonic tone and reduces anxiety, while at high doses, there is an increase in tense arousal, including anxiety, nervousness, jitteriness. The larger improvement of performance in fatigued subjects confirms that caffeine is a mild stimulant. Caffeine has also been reported to prevent cognitive decline in healthy subjects but the results of the studies are heterogeneous, some finding no age-related effect while others reported effects only in one sex and mainly in the oldest population. In conclusion, it appears that caffeine cannot be considered a ;pure' cognitive enhancer. Its indirect action on arousal, mood and concentration contributes in large part to its cognitive enhancing properties.
Although the subjective effects of caffeine abstinence, acute and chronic administration, and tolerance are well described, the corresponding neurophysiological effects are not.
Caffeine withdrawal, acute caffeine effects, caffeine tolerance, and net beneficial effects of chronic caffeine administration were investigated using cerebral blood flow velocity, quantitative electroencephalography (EEG), and subjective effects.
Sixteen regular caffeine users participated in this double-blind, within-subject study during which they received acute caffeine and placebo challenges (1) while maintained on 400 mg caffeine daily for > or =14 days and (2) while maintained on placebo for > or =14 days. Blood flow velocity was determined for the middle (MCA) and anterior (ACA) cerebral arteries using pulsed transcranial Doppler sonography. EEG was recorded from 16 scalp sites. Subjective effects were assessed with questionnaires.
Acute caffeine abstinence (evaluated 24 h after placebo substitution) increased mean, systolic, and diastolic velocity in the MCA and ACA and decreased pulsatility index in the MCA. Acute caffeine abstinence increased EEG theta and decreased beta 2 power. Acute caffeine abstinence also increased measures of Tired, Fatigue, Sluggish, and Weary and decreased ratings of Energetic, Friendly, Lively, and Vigor. Acute caffeine effects were demonstrated across a wide range of measures, including cerebral blood flow, EEG, and subjective effects. Tolerance and "complete" tolerance were observed on subjective but not physiological measures. Chronic caffeine effects were demonstrated only on the measure of EEG beta 2 power.
Acute caffeine abstinence and administration produced changes in cerebral blood flow velocity, EEG, and subjective effects. Tolerance to subjective but not physiological measures was demonstrated. There was almost no evidence for net effects of chronic caffeine administration on these measures. Overall, these findings provide the most rigorous demonstration to date of physiological effects of caffeine withdrawal.
Some previous studies have demonstrated an early effect of caffeine administration on subjective state, but none of them has explored its existence after the administration of decaffeinated coffee, or the possible differences depending on the gender and circadian typology of the subjects. The aim of the present work is to investigate the early effects (10-30 min post-consumption) of a single low dose of caffeine (100 mg) and decaffeinated coffee on sleepiness, subjective activation and affect using a realistic design. The influence of gender and circadian typology is also explored.
A randomized double-blind informed placebo controlled procedure was applied to 688 healthy undergraduate volunteers, mean age 22.03+/-2.21 years, 238 men and 450 women. Measures were recorded before and after beverage consumption (10, 20 and 30 min), in two experimental sessions: morning 11:00-13:00 h or afternoon 16:00-18:00 h.
Caffeine administration induced arousing effects (lesser somnolence and greater activation) in all post-consumption records, while the effects of decaffeinated drink were only apparent at 10 min. Caffeine effects were greater in men, and the decaffeinated beverage produced greater effects in women. Circadian typology only showed effects for time of day (morning/afternoon) related with rhythmic expression.
Future works should study more accurately the early effect of coffee beverages and the influence of gender, using other parameters which have proven to be sensitive to their administration. The effect of several caffeine doses should also be studied.
There is a vast literature on the behavioural effects of caffeine. Many of the studies have involved single administration of a large dose of caffeine that is not representative of the way in which caffeine is usually ingested. Further information is required, therefore, on the behavioural effects of realistic patterns of consumption.
The present study aimed to determine whether a realistic drinking regime (multiple small doses - 4 x 65 mg over a 5-h period) produced the same effects as a single large dose (200 mg). The smaller doses were selected so that the amount of caffeine present in the body after 5 h would be equivalent to that found with the single dose.
A double-blind, placebo-controlled, within-subjects experiment was, therefore, carried out. The participants ( n=24) attended for four sessions. Each session started with a baseline measurement of mood and performance at 0930 hours. On two of the sessions, coffee was then consumed at 1000, 1100, 1200 and 1300 hours. In one of these sessions 65 mg caffeine was added to the de-caffeinated coffee. In the other two sessions, the participants consumed coffee at 1300 hours and 200 mg caffeine was added in one of the sessions. The volunteers completed the battery of tests again at 1500 hours.
The results showed that in both consumption regimes caffeine led to increased alertness and anxiety and improved performance on simple and choice reactive tasks, a cognitive vigilance task, a task requiring sustained response and a dual task involving tracking and target detection.
These results suggest that previous findings from studies using a large single dose may be applicable to normal patterns of caffeine consumption.
The adenosine receptor system, which mediates the psychoactive effects of caffeine, is also thought to be involved in the regulation of anxiety. In this study, we examined the association between variations in anxiogenic responses to caffeine and polymorphisms in the A1 and A2a adenosine receptor genes. Healthy, infrequent caffeine users (N=94) recorded their subjective mood states following a 150 mg oral dose of caffeine freebase or placebo in a double-blind study. We found a significant association between self-reported anxiety after caffeine administration and two linked polymorphisms on the A2a receptor gene, the 1976C>T and 2592C>Tins polymorphisms. Individuals with the 1976T/T and the 2592Tins/Tins genotypes reported greater increases in anxiety after caffeine administration than the other genotypic groups. The study shows that an adenosine receptor gene polymorphism that has been associated with Panic Disorder is also associated with anxiogenic responses to an acute dose of caffeine.
This review aims to determine whether, and to what extent, dietary caffeine may be a risk to cardiovascular health.
A critical review of the relevant experimental and epidemiologic literature was conducted, with particular reference to studies of caffeine and blood pressure (BP).
There is extensive evidence that caffeine at dietary doses increases BP. However, concern that the drug may contribute to cardiovascular disease appears to have been dampened by (1) the belief that habitual use leads to the development of tolerance, and (2) confusion regarding relevant epidemiologic findings. When considered comprehensively, findings from experimental and epidemiologic studies converge to show that BP remains reactive to the pressor effects of caffeine in the diet. Overall, the impact of dietary caffeine on population BP levels is likely to be modest, probably in the region of 4/2 mm Hg. At these levels, however, population studies of BP indicate that caffeine use could account for premature deaths in the region of 14% for coronary heart disease and 20% for stroke.
Current evidence supports the conclusion that the BP-elevating effects of dietary caffeine may be contributing appreciably to population levels of cardiovascular mortality and morbidity. Accordingly, strategies for encouraging reduced dietary levels of caffeine deserve serious consideration.
Although reports of caffeine withdrawal in the medical literature date back more than 170 years, the most rigorous experimental investigations of the phenomenon have been conducted only recently.
The purpose of this paper is to provide a comprehensive review and analysis of the literature regarding human caffeine withdrawal to empirically validate specific symptoms and signs, and to appraise important features of the syndrome.
A literature search identified 57 experimental and 9 survey studies on caffeine withdrawal that met inclusion criteria. The methodological features of each study were examined to assess the validity of the effects.
Of 49 symptom categories identified, the following 10 fulfilled validity criteria: headache, fatigue, decreased energy/activeness, decreased alertness, drowsiness, decreased contentedness, depressed mood, difficulty concentrating, irritability, and foggy/not clearheaded. In addition, flu-like symptoms, nausea/vomiting, and muscle pain/stiffness were judged likely to represent valid symptom categories. In experimental studies, the incidence of headache was 50% and the incidence of clinically significant distress or functional impairment was 13%. Typically, onset of symptoms occurred 12-24 h after abstinence, with peak intensity at 20-51 h, and for a duration of 2-9 days. In general, the incidence or severity of symptoms increased with increases in daily dose; abstinence from doses as low as 100 mg/day produced symptoms. Research is reviewed indicating that expectancies are not a prime determinant of caffeine withdrawal and that avoidance of withdrawal symptoms plays a central role in habitual caffeine consumption.
The caffeine-withdrawal syndrome has been well characterized and there is sufficient empirical evidence to warrant inclusion of caffeine withdrawal as a disorder in the DSM and revision of diagnostic criteria in the ICD.
Although it is widely believed that caffeine can enhance human performance and mood, the validity of this belief has been questioned, giving rise to debate. The central question is whether superior performance and mood after caffeine represent net benefits, or whether differences between caffeine and control conditions are due to reversal of adverse withdrawal effects.
To provide a focussed review of relevant experimental studies with the aim of clarifying current understanding regarding the effects of caffeine on human performance and mood.
To avoid the shortcomings of standard placebo-controlled studies, which are ambiguous due to failure to control for the confounding influence of withdrawal reversal, three main experimental approaches have been employed: studies that compare consumers and low/non-consumers, pre-treatment and ad lib consumption studies, and long-term withdrawal studies.
Of the three approaches, only long-term withdrawal studies are capable of unambiguously revealing the net effects of caffeine. Overall, there is little evidence of caffeine having beneficial effects on performance or mood under conditions of long-term caffeine use vs abstinence. Although modest acute effects may occur following initial use, tolerance to these effects appears to develop in the context of habitual use of the drug.
Appropriately controlled studies show that the effects of caffeine on performance and mood, widely perceived to be net beneficial psychostimulant effects, are almost wholly attributable to reversal of adverse withdrawal effects associated with short periods of abstinence from the drug.
Caffeine produces mild psychostimulant and sometimes anxiogenic effects by antagonizing adenosine at A(1) and A(2A) receptors, and perhaps through interactions with other transmitter systems. Adenosine receptors are colocalized and functionally interact with dopamine receptors in the brain. Thus, functional polymorphisms in the genes for either adenosine or dopamine receptors may affect responses to caffeine. In this study, we examined associations between self-reported anxiogenic effects of caffeine and variation in the genes for A(2A) (ADORA2A) and DRD(2) (DRD2) receptors. Healthy male and female individuals (n=102), who consumed less than 300 mg caffeine per week, ingested capsules containing 0, 50, 150, and 450 mg caffeine under double-blind conditions in four separate experimental sessions. Subjective anxiety was measured before and at repeated times after capsules were consumed. At the 150 mg dose of caffeine, we found a significant association between caffeine-induced anxiety (Visual Analog Scales, VAS) and ADORA2A rs5751876 (1976C/T), rs2298383 (intron 1a) and rs4822492 (3'-flank), and DRD2 rs1110976 (intron 6). Caffeine-induced anxiety (VAS) was also associated with two-loci interactions of selected ADORA2A and DRD2 polymorphisms. The lowest dose of caffeine did not increase ratings of anxiety while the highest dose increased anxiety in the majority of subjects. These findings provide support for an association between an ADORA2A polymorphism and self-reported anxiety after a moderate dose of caffeine. It is likely that other ADORA2A and DRD2 polymorphisms also contribute to responses to caffeine.
Over the past decade, many lines of investigation have shown that receptor-mediated signaling exhibits greater diversity than previously appreciated. Signal diversity arises from numerous factors, which include the formation of receptor dimers and interplay between different receptors. Using adenosine A(1) receptors as a paradigm of G protein-coupled receptors, this review focuses on how receptor-receptor interactions may contribute to regulation of the synaptic transmission within the central nervous system. The interactions with metabotropic dopamine, adenosine A(2A), A(3), neuropeptide Y, and purinergic P2Y(1) receptors will be described in the first part. The second part deals with interactions between A(1)Rs and ionotropic receptors, especially GABA(A), NMDA, and P2X receptors as well as ATP-sensitive K(+) channels. Finally, the review will discuss new approaches towards treating neurological disorders.
Coffee, consumed for its refreshing and stimulating effect, belongs to the tribe Coffea of the subfamily Cinchonoidea of Rubiaceae family. Coffee is a complex chemical mixture composed of several chemicals. It is responsible for a number of bioactivities and a number of compounds accounting for these effects. Few of the significant bioactivities documented are antioxidant activity, anticarcinogenic activity, antimutagenic activity etc. Various compounds responsible for the chemoprotective effects of coffee are mainly polyphenols including chlorogenic acids and their degradation products. Others include caffeine, kahweol, cafestol, and other phenolics. Coffee also shows protective or adverse effects on various systems like the skeletal (bone) system, the reproductive system, the nervous system, the cardiovascular system, the homocysteine levels, the cholesterol levels etc. Harmful effects of coffee are associated with people who are sensitive to stimulants. Overall, with the available information, it can be concluded that the moderate consumption, corresponding to 3 to 4 cups/day with average strength is safer to human health.
Psychiatrists rarely enquire about caffeine intake when assessing patients. This may lead to a failure to identify caffeine-related problems and offer appropriate interventions. Excessive caffeine ingestion leads to symptoms that overlap with those of many psychiatric disorders. Caffeine is implicated in the exacerbation of anxiety and sleep disorders, and people with eating disorders often misuse it. It antagonises adenosine receptors, which may potentiate dopaminergic activity and exacerbate psychosis. In psychiatric in-patients, caffeine has been found to increase anxiety, hostility and psychotic symptoms. Assessment of caffeine intake should form part of routine psychiatric assessment and should be carried out before prescribing hypnotics. Gradual reduction in intake or gradual substitution with caffeine-free alternatives is probably preferable to abrupt cessation. Decaffeinated beverages should be provided on psychiatric wards.
Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal.
Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes.
GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation=0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35.
There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes.
Effects of nicotine and caffeine, separately and in combination, were assessed in 12 male habitual smokers in a repeated-measures design. Caffeine (0-mg vs. two 150-mg doses administered in a decaffeinated/sugar-free cola drink post-baseline and 90 min later) was crossed with nicotine (ad libitum own dosing vs. 1.0-mg machine-delivered dose vs. 0.05-mg machine-delivered dose). Participants smoked a total of five cigarettes at 30-min intervals over a 2-hr period. Caffeine and nicotine had large effect sizes on electroencephalogram (EEG) power; however, these effects were modulated by the eyes open versus closed condition, the other drug, and electrode site. EEG effects of open versus closed eyes tended to be of the same size and direction as those of nicotine and caffeine. However, whereas nicotine increased EEG power in some higher frequency bands in some conditions, caffeine decreased EEG power across almost all conditions. Serum cortisol concentration, vigor, and pleasantness were increased by nicotine, but not by caffeine. Level of depressive mood depended on an interaction of caffeine and nicotine. Vigilance performance was enhanced significantly by caffeine and was increased almost significantly by nicotine. The findings were interpreted in terms of common and differential mechanisms of the two drugs.
Our aim was to observe the induction of anxiety symptoms and panic attacks by a caffeine challenge test in panic disorder (PD) patients (DSM-IV) and their healthy first-degree relatives. We randomly selected 25 PD patients, 27 healthy first-degree relatives of probands with PD, and 22 healthy volunteers with no family history of PD. In a randomized double-blind experiment performed over two occasions 7 days apart, 480 mg caffeine and a caffeine-free solution were administered in a coffee form. Using specific panic attack criteria, 52.0% (n=13) PD patients, 40.7% (n=11) first-degree relatives (χ2=1.81, df=1, P=0.179), and none of the control subjects had a panic attack after the test (χ2=51.7, df=2, P<0.001). In this caffeine challenge test, PD patients and their first-degree relatives were more sensitive than healthy volunteers to the panic attack symptoms but less sensitive to headache, increase in blood pressure, and insomnia. Our data suggest that there is an association between panic attacks after the intake of 480 mg of caffeine in PD patients and their first-degree relatives. There is a clear differentiation of PD patients and their first-degree relatives by a caffeine test from the healthy group. Depression and Anxiety, 2008. © 2007 Wiley-Liss, Inc.
Studies have demonstrated the vulnerability of anxiety disorder patients to challenge tests. Our aim was to observe if panic disorder (PD) patients and generalized social anxiety disorder (GSAD) and performance social anxiety disorder (PSAD) patients respond in a similar way to the induction of anxiety symptoms and panic attacks by an oral caffeine challenge test. We compared 28 PD patients, 25 GSAD patients, 19 PSAD, and 26 control subjects after a 480-mg caffeine test. The patients had not received psychotropic drugs for at least a 4-week period. In a randomized double-blind experiment performed in two occasions 7 days apart, 480 mg of caffeine and a caffeine-free solution were administered and anxiety scales were administered before and after each test. A panic attack was induced in 17 (60.7%) PD patients, 4 (16.0%) GSAD patients, and 10 (52.6%) PSAD patients, during the caffeine test. None of the control subjects had a panic attack after the caffeine intake. Neither patients nor any control subject had a panic attack after drinking the caffeine-free solution. Our data suggest that there is an association between PD and PSAD hyperreactivity to an oral caffeine challenge test. The PD and PSAD patients had a higher number of induced panic attacks, some specific anxiety symptoms, and a more severe anxiety response than GSAD patients and normal volunteers.
Caffeine is widely consumed in beverages and food, and its consumption in high doses is associated with anxiety increase. Stress situations are often associated to coffee consumption, and have a strong influence on oxidative DNA damage. As there are sex-specific differences in many metabolic, neurochemical and behavioral aspects, the aim of this study is to verify the interaction between chronic consumption of caffeine and chronic stress on anxiety and DNA breaks in the hippocampus on male and female rats. Wistar rats were submitted to restraint stress for at least 50 days. The diet consisted of standard rat chow and caffeine 0.3 or 1 g/L in drinking water "ad libitum" as the only drinking source. Controls received tap water. Anxiety-like behavior and DNA breaks in the hippocampus were evaluated. Caffeine consumption and chronic stress increased anxiety-like behavior as well as DNA breaks in the hippocampus of male rats. No effect on these parameters was observed in females. These results may be related to the presence of estradiol, which may have anxiolytic and neuroprotective properties.
The effects of oral administration of caffeine (10 mg/kg) on behavioral ratings, somatic symptoms, blood pressure and plasma levels of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) and cortisol were determined in 17 healthy subjects and 21 patients meeting DSM-III criteria for agoraphobia with panic attacks or panic disorder. Caffeine produced significantly greater increases in subject-rated anxiety, nervousness, fear, nausea, palpitations, restlessness, and tremors in the patients compared with healthy subjects. In the patients, but not the healthy subjects, these symptoms were significantly correlated with plasma caffeine levels. Seventy-one percent of the patients reported that the behavioral effects of caffeine were similar to those experienced during panic attacks. Caffeine did not alter plasma MHPG levels in either the healthy subjects or patients. Caffeine increased plasma cortisol levels equally in the patient and healthy groups. Because caffeine is an adenosine receptor antagonist, these results suggest that some panic disorder patients may have abnormalities in neuronal systems involving adenosine. Patients with anxiety disorders may benefit by avoiding caffeine-containing foods and beverages.
The phamacokinetic behavior of caffeine was compared in a group of eight healthy young men aged 20.5±2.0 years (mean ± SD), and in a group of eight healthy, elderly men aged 71.2±3.9 years. Each subject was given a 5 mg/kg dose of caffeine as either an aqueous oral solution or an intravenous infusion over 30 min using a randomized crossover design. Plasma and urine samples were collected for 24 hr following each dose and analyzed for caffeine content using high-performance liquid chromatography.
The peak times (tmax), peak concentrations (Cmax), and the percentage of the peroral dose systemically available, F(%), were essentially identical in both age groups, indicating that caffeine was absorbed rapidly and completely after peroral administration. These results also indicated that the first-pass metabolism observed in rats following the peroral administration of caffeine does not occur in either human group studied here. The elimination of caffeine during its terminal disposition phase was log-linear. Several between-group comparisons of other pharmacokinetic parameters were made. Although the average elimination rate constant was greater in the elderly, the difference did not reach statistical significance, possibly because of the considerable intersubject variability in the elimination rate of caffeine, with halflives ranging from 2.27 to 9.87 hr. The average apparent volume of distribution was significantly lower in the elderly subjects while the clearances were slightly, but not significantly, larger in the elderly subjects. It appears that most aspects of the pharmacokinetic behavior of caffeine are very similar in young and elderly men.
To investigate the reliability and validity of DSM-III-R "generalized" social phobia by examining interrater agreement and comparing patients with generalized and "nongeneralized" social phobia on demographic characteristics, clinical variables, and familial social phobia.
Two senior clinicians classified 129 patients attending an anxiety clinic as having DSM-III-R social phobia that is generalized (fears most social situations) or nongeneralized (less than most) based on independent narrative review.
Good reliability was achieved (kappa = 0.69). Patients with generalized social phobia were more often single, had earlier onsets of social phobia, had more interactional fears, and had higher rates of atypical depression and alcoholism. Familial social phobia was more common among patients with generalized social phobia than patients with nongeneralized social phobia and controls, with no difference between the latter two groups.
Generalized social phobia (1) can be distinguished reliably from nongeneralized social phobia, (2) is a valid subtype, and (3) may characterize a familial form of the disorder.
The uses and effects of caffeine as a psychoactive drug in chronic psychiatric inpatient groups are described. Caffeine use and abuse is linked etiologically to diverse psychiatric disorders; its mechanisms of action are examined in relation to anxiety, anxiety neuroses, psychosis, schizophrenia, and caffeine intoxication and dependence. It is postulated that deleterious effects may result from the interaction of caffeine with commonly prescribed psychotropic drugs. A possible model of caffeine abuse is discussed. Increased public education about potential health problems related to caffeine consumption is suggested, and further controls of caffeine in psychiatric settings are recommended.
Caffeine has both positive effects that contribute to widespread consumption of caffeine-containing beverages and adverse unpleasant effects if doses are increased. Caffeine has weak reinforcing properties, but with little or no evidence for upward dose adjustment, possibly because of the adverse effects of higher doses. Withdrawal symptoms, although relatively limited with respect to severity, do occur, and may contribute to maintenance of caffeine consumption. Health hazards are small if any and caffeine use is not associated with incapacitation. Thus, although caffeine can be argued to fulfill regulatory criteria as a dependence-producing drug, the extensive use of caffeine-containing beverages poses little apparent risk to the consumer or to society. The positive stimulatory effects of caffeine appear in large measure to be due to blockade of A2A receptors that stimulate GABAergic neurons of inhibitory pathways to the dopaminergic reward system of the striatum. However, blockade of striatal A1 receptors may also play a role. The mechanisms underlying negative effects of higher doses of caffeine are as yet not well defined.
Rationale:
The effects of caffeine, especially caffeinated coffee, on human performance have been extensively studied. However, few studies have been naturalistic representations of how tea/coffee is normally consumed in terms of dose and time of consumption.
Objectives:
This study investigated the effects of day-long consumption of tea, coffee and water on cognitive and psychomotor performance, and sleep quality at night.
Methods:
Thirty healthy volunteers received equal volume drinks equivalent to either 1 or 2 cups of tea (containing 37.5 mg or 75 mg caffeine), or coffee (75 mg or 150 mg caffeine), or water, in a randomised five-way crossover design. Drinks were administered on four occasions during the day (0900, 1300, 1700 and 2300 hours). A psychometric battery consisting of critical flicker fusion (CFF), choice reaction time (CRT) and subjective sedation (LARS) tests, was administered pre-dose and at frequent time points post-dose. The Leeds Sleep Evaluation Questionnaire (LSEQ) was completed each morning and a wrist actigraph was worn for the duration of the study.
Results:
Caffeinated beverages maintained CFF threshold over the whole day (P<0.05), independent of caffeine dose or beverage type. During the acute phase of beverage ingestion, caffeine significantly sustained performance compared to water after the first beverage for CFF and subjective sedation (P<0.05), and after the second beverage for the Recognition component of the CRT task (P<0.05). Additionally, there were significant differences between tea and coffee at 75 mg caffeine after the first drink. Compared to coffee, tea produced a significant increase in CFF threshold between 30 and 90 min post-consumption (P<0.01). However, following the second beverage caffeinated coffee at 75 mg significantly improved reaction time (P<0.05), compared to tea at the same dose, for the Recognition component of the CRT task. Caffeinated beverages had a dose dependent negative effect on sleep onset (P<0.001), sleep time (P<0.001) and sleep quality (P<0.001).
Conclusions:
These results indicate that ingestion of caffeinated beverages may maintain aspects of cognitive and psychomotor performance throughout the day and evening when caffeinated beverages are administered repeatedly. This study also demonstrates that day-long tea consumption produces similar alerting effects to coffee, despite lower caffeine levels, but is less likely to disrupt sleep. Other differences between tea and coffee were more subtle, and require further investigation.
The subjective effects of caffeine, the most widely used psychoactive drug, vary widely from person to person. The factors responsible for these individual differences remain largely unknown. Data from 36 healthy adults who were light to moderate users of caffeine were examined with the goals of characterizing the subjective effects of caffeine and identifying factors which might correlate with or predict these effects. Subjective effects of 100 and 300 mg caffeine were measured with standardized questionnaires. The low dose of caffeine was found to produce negligible subjective effects in the group as a whole, while the high dose produced mild stimulant and anxiogenic effects. As expected, there was considerable intersubject variability in the subjective effects of caffeine. There was no correlation between stimulant and anxiogenic effects after the high dose. Light caffeine users were more accurate than heavy caffeine users in identifying the high dose of caffeine as an active drug, but there was no evidence that light users were generally more sensitive to the subjective effects of caffeine. Current alcohol use, prior recreational use of stimulants, and baseline level of self-reported arousal appeared to influence subjective response to caffeine. Other variables (personality, gender, baseline anxiety, and prior use of other drugs) showed no relationship with mood res ponse to caffeine.
(C) Lippincott-Raven Publishers.
Estimation of the passage of time in the seconds-to-minutes range and reaction time are strongly dependent on a hypothetical internal clock. Dopamine is the neurotransmitter most closely related to the rate of this clock. Caffeine, probably the most consumed drug in the world, leads to an augmentation of dopamine neurotransmission. In this study coffee, which reproduces the conditions under which caffeine is normally ingested, containing 3, 75, 150 or 300 mg of caffeine, was given to healthy male and female volunteers. A computerized time estimation and reaction time test was carried out 50 min after ingestion. Sex differences in placebo control subjects (who took decaffeinated coffee with 3 mg of caffeine), with females making more accurate estimates of time intervals than males and males showing shorter reaction times than females, were removed in subject taking doses of 75 and 150 mg of caffeine in the case of time estimation and 150 mg in the case of reaction time. The 300 mg dose induced overestimation of time in females and shortened the reaction time in males. There were no sex differences in the pharmacokinetics of caffeine, as measured in salivary concentration of caffeine using high-performance liquid chromatography. Results indicating sex differences in time estimation or reaction time should not be generalized from the laboratory to real life without considering the fact that everyday coffee consumption may eliminate these differences. Copyright 2001 John Wiley & Sons, Ltd.
Coffee, reproducing the conditions under which caffeine is normally ingested, containing 3, 75, 150 or 300 mg of caffeine was given to healthy male and female volunteers. 25-30 min after drinking the beverage, they completed the Spanish version of the state-trait anxiety inventory (STAI). The beverage increased state anxiety, in a dose-dependent manner, in males but not in females. This could be due to a lesser sensitivity of females to coffee.
Coffee is a complex mixture of chemicals that provides significant amounts of chlorogenic acid and caffeine. Unfiltered coffee is a significant source of cafestol and kahweol, which are diterpenes that have been implicated in the cholesterol-raising effects of coffee. The results of epidemiological research suggest that coffee consumption may help prevent several chronic diseases, including type 2 diabetes mellitus, Parkinson's disease and liver disease (cirrhosis and hepatocellular carcinoma). Most prospective cohort studies have not found coffee consumption to be associated with significantly increased cardiovascular disease risk. However, coffee consumption is associated with increases in several cardiovascular disease risk factors, including blood pressure and plasma homocysteine. At present, there is little evidence that coffee consumption increases the risk of cancer. For adults consuming moderate amounts of coffee (3-4 cups/d providing 300-400 mg/d of caffeine), there is little evidence of health risks and some evidence of health benefits. However, some groups, including people with hypertension, children, adolescents, and the elderly, may be more vulnerable to the adverse effects of caffeine. In addition, currently available evidence suggests that it may be prudent for pregnant women to limit coffee consumption to 3 cups/d providing no more than 300 mg/d of caffeine to exclude any increased probability of spontaneous abortion or impaired fetal growth.
Caffeine produces mild psychostimulant effects that are thought to underlie its widespread use. However, the direct effects of caffeine are difficult to evaluate in regular users of caffeine because of tolerance and withdrawal. Indeed, some researchers hypothesize that the psychostimulant effects of caffeine are due largely to the reversal of withdrawal and question whether there are direct effects of caffeine consumption upon mood, alertness, or mental performance in nondependent individuals.
This study investigated the physiological, subjective, and behavioral effects of 0, 50, 150, and 450 mg caffeine in 102 light, nondependent caffeine users.
Using a within-subjects design, subjects participated in four experimental sessions, in which they received each of the four drug conditions in random order under double blind conditions. Participants completed subjective effects questionnaires and vital signs were measured before and at repeated time points after drug administration. Forty minutes after the capsules were ingested, subjects completed behavioral tasks that included tests of sustained attention, short-term memory, psychomotor performance, and behavioral inhibition.
Caffeine significantly increased blood pressure, and produced feelings of arousal, positive mood, and high. Caffeine increased the number of hits and decreased reaction times in a vigilance task, but impaired performance on a memory task.
We confirm that acute doses of caffeine, at levels typically found in a cup of coffee, produce stimulant-like subjective effects and enhance performance in light, nondependent caffeine users. These findings support the idea that the drug has psychoactive effects even in the absence of withdrawal.
Although caffeine is the most commonly used psychoactive substance and often produces symptoms of toxicity and dependence, little is known, especially in community samples, about the association between caffeine use, toxicity and dependence and risk for common psychiatric and substance use disorders.
Assessments of lifetime maximal caffeine use and symptoms of caffeine toxicity and dependence were available on over 3600 adult twins ascertained from the population-based Virginia Twin Registry. Lifetime histories of major depression (MD), generalized anxiety disorder (GAD) and panic disorder, alcohol dependence, adult antisocial behavior and cannabis and cocaine abuse/dependence were obtained at personal interview. Logistic regression analyses in the entire sample and within monozygotic (MZ) twin pairs were conducted in SAS.
In the entire sample, measures of maximal caffeine use, heavy caffeine use, and caffeine-related toxicity and dependence were significantly and positively associated with all seven psychiatric and substance use disorders. However, within MZ twin pairs, controlling for genetic and family environmental factors, these associations, while positive, were all non-significant. These results were similar when excluding twins who denied regular caffeine use.
Maximal lifetime caffeine intake and caffeine-associated toxicity and dependence are moderately associated with risk for a wide range of psychiatric and substance use disorders. Analyses of these relationships within MZ twin pairs suggest that most of the observed associations are not causal. Rather, familial factors, which are probably in part genetic, predispose to both caffeine intake, toxicity and dependence and the risk for a broad array of internalizing and externalizing disorders.
Our aim was to compare the demographic and clinical features of panic disorder (PD) patients with agoraphobia-DSM-IV-who had a panic attack after both an oral caffeine and the 35% carbon dioxide (CO2) challenge tests (responsive group) and compare them with PD patients who did not have a panic attack after both tests (non-responsive group). We examined 83 PD patients submitted to a 35% CO2 test and to an oral caffeine (480 mg) intake within 1 week interval. A panic attack was induced in 51 (61.4%) patients during the CO2 test (chi2=31.67, df=1, p<0.001) and in 38 (45.8%) patients during the caffeine test (chi2=18.28, df=1, p=0.023). All patients who had a panic attack during the caffeine test also had a panic attack during the CO2 test (n=38)-responsive group. The responsive had more (chi2=24.55, df=1, p=0.008) respiratory PD subtype, disorder started earlier (Mann-Whitney, p<0.001) had a higher familial prevalence of PD (chi2=20.34, df=1, p=0.019), less previous alcohol abuse (chi2=23.42, df=1, p<0.001), and had more previous depressive episodes (chi2=27.35, df=1, p<0.001). Our data suggest that there is an association between respiratory PD subtype and hyperreactivity to challenge tests: CO2 and oral caffeine.
Nutritional neuroscience
- Prasad Ch
Prasad Ch. Nutritional neuroscience. Boca Raton (FL): CRC Press; 2005.
Coffee, tea, chocolate, and the brain
- A Nehlig
Nehlig A. Coffee, tea, chocolate, and the brain. Boca Raton (FL): CRC
Press; 2004.
Coffee and health: a review of recent human research
- J V Higdon
- B Frey
Higdon JV, Frey B. Coffee and health: a review of recent human
research. Crit Rev Food Sci 2006;46:101-23.
Lactate response to caffeine in panic disorder: a replication using an "anxious" control group
- M E Tancer
- M B Stein
- T W Uhde
Tancer ME, Stein MB, Uhde TW. Lactate response to caffeine in
panic disorder: a replication using an "anxious" control group. Biol
Psychiatry 1991;29:57A.
Neurobiology of panic disorder. Frontiers of clinical neuroscience
- T W Uhde
Uhde TW. Caffeine provocation of panic: a focus on biological
mechanisms. In: Ballenger J, editor. Neurobiology of panic disorder. Frontiers of clinical neuroscience. New York: Alan R. Liss; 1990.
pp. 365-76.
Anxiogenic effects of caffeine on panic and depressed patients
- M A Lee
- P Flegel
- J F Greden
- O G Cameron
Lee MA, Flegel P, Greden JF, Cameron OG. Anxiogenic effects
of caffeine on panic and depressed patients. Am J Psychiatry
1988;145:632-5.