Caffeine

BACKGROUND
Caffeine, nicotine and alcohol are probably the three most widely used psychoactive chemical agents in the world. Caffeine is generally used as a beverage in coffee, tea and soda pop drinks. It is non-prescription drug where per capita intake for the entire world's population approximates 70 mg a day, but in the United States that figure exceeds 200 mg. and four out of five adult Americans report regular intake.

Caffeine's use apparently dates back thousands of years - tea in China to 5000 years ago, Coffee beans in Africa to 1500 years ago, Coffee in Arabia to 800 years ago.

Pharmacologically, caffeine belongs to a brain stimulant group of alkaloids called methylxanthines (also called xanthines). Theophylline and Theobromine are also Xanthines.

OCCURRENCE
It occurs naturally in some plants nuts, seeds or leaves.

e.g. Coffee from the Coffea arabica plant;

soft drinks, like Cola drinks, made from Kola nuts ( but less than 5% of the caffeine is from the kola nut; the other 95% uses the decaffeination extract process results)

tea leaves from Thea sinensis.

Cocoa is from the seeds of the Theobroma cocoa plant (or cocoa beans) and is used to make chocolate, chocolate milk, hot cocoa, and various other candies. This contains mainly theobromine. A candy bar (3.5 ounces) may contain caffeine (e.g. 12 mg) and theobromine (e.g. 155 mg) and a 5 ounce hot cocoa cup, 10 mg caffeine and 200 mg theobromine.

CAFFEINE USES:
1. Food additive :This is regulated by the Federal Food and Drug Administration (FDA) with a label insert when caffeine has been added.

2. Natural usage of Caffeine need not be on the label.e.g. coffee, tea, soft drinks, chocolate candy bars

3. Over-the-counter and prescription medications e.g. stimulants with antimigraine or antihistamine drugs, cold remedies, and pain killers. Use relates to management of side-effects or symptoms of fatigue and hyperactivity (questionable).

PHARMACOLOGICAL EFFECTS
Biological effects of caffeine in animals and man depend on the dose, method of administration and duration of exposure.

Technically, caffeine enhances CNS norepinephrine secretion, inhibits phosphodiesterase breakdown of cyclic 3',5'-adenosine monophosphate (cAMP) at high concentrations, sensitizes central catecholamine postsynaptic receptors (including those for dopamine), enhances cyclic guanosine 3',5'-monophosphate (cGMP), and modulates acetylcholine and serotonin activity. Caffeine induces significant increases in cortisol, but no meaningful change in prolactin.

Caffeine's ability to antagonize adenosine receptors in the brain probably accounts for the most important of the drug's behavioral effects. Adenosine is an important CNS neuromodulator, possessing sedative, anxiolytic, and anticonvulsant properties. Adenosine also dilates blood vessels in cerebral and coronary circulatory networks. Caffeine competes with adenosine for binding at its high-affinity receptor sites, preventing adenosine's normal tranquilizing or sedating effects. Thus, caffeine's stimulant or anxiety-inducing actions appear to be secondary effects of adenosine antagonism. Chronic caffeine exposure has also been shown to induce heterologous up-regulation of adenosine receptors in humans. Caffeine's antagonism to vasodilation by adenosine may account for caffeine withdrawal headaches, as well as for its efficacy in treating migraine headaches.

Positron emission tomography (PET) imaging studies confirm that a caffeine dose of 200 mg produces a diffusely decreases cerebral blood flow by about a third within an hour of administration

MEDICAL EFFECTS
Caffeine is a mild stimulant and people have variable sensitivity to caffeine. Caffeine does not accumulate in the blood and is normally excreted within several hours. It can speed reaction time, prolong vigilance but will not help people "sober up" to too much alcohol.

Caffeine is the single most important cause of anxiety in our society and doses like 1000 mg per day is anxiety evoking in almost everyone and many are exquisitely sensitive e.g. 50 mg or 100 mg. This may lead to misdiagnoses of Panic or Generalized Anxiety Disorder. Caffeine may impair sleep in sensitive individuals and is not advised at night in insomniacs.
In addition to other psychiatric or medical conditions, concomitant use of other psychoactive agents, such as nicotine, alcohol, or benzodiazepines, is common in caffeine users. This often confounds an accurate diagnosis.

Caffeine is, at this point, regarded as safe for long term use in regard to its physical effects:
* May 1987, FDA "studies on teratology, reproduction behavior, carcinogenicity, and cardiovascular disease...found no evidence to show that the use of caffeine in carbonated beverages would render these beverages injurious to health."
* 1984 AMA Council on Scientific Affairs "Moderate tea or coffee drinkers probably need have no concern for their health relative to their caffeine consumption provided other lifestyle habits (diet, alcohol consumption) are moderate, as well."

Available information does not suggest a recommendation against the moderate use of coffee unless it is known to cause specific symptoms, like anxiety, agitation or palpitations, in the individual using it. There is no indication that caffeine, a natural component of both coffee and tea, is a risk factor in human cancer.

Coffee, tea and other caffeinated beverages do not cause any persistent increase in blood pressure.though some individuals may experience a small, short-lived rise in blood pressure usually not lasting more than several hours.
Most scientific research does not support a link between caffeine consumption and cardiovasculardisease - weak and inconsistent evidence or 1989 Framingham Heart Study "no deleterious or salutary effect of coffee consumption."

1990 Harvard University study: Caffeine intake does not appreciably increase the risk of coronary heart disease or stroke. Individual patients may find the frequency or severity of cardiac arrhythmias increasing, but generally not.

Three major studies involving more than 15,000 women have found no birth defects associated with caffeine consumption. Even offspring of the heaviest coffee drinkers were not found to be at higher risk of birth defects, spontaneous abortion or preterm delivery, or dysmaturity.
The most recent FDA animal studies have found no birth defects when rats are given high doses of caffeine in their drinking water. These results contradict earlier FDA research in 1980 that had triggered an advisory to pregnant women to avoid caffeine involving force-fed rats high doses of caffeine all at once through stomach tubes (gavage).

Caffeine may adversely affect reproduction in humans , but variables in like exercise level, dietary habits, stress, were not controlled.

Children are no more sensitive to caffeine's potential effects than adults and it may be eliminated from the body twice as rapidly in children than adults.

Caffeine consumption patterns differ somewhat from drugs of dependence.

1. It does not result in steadily increased doses over short periods. However, caffeine use generally increases gradually over the years). Consumption often surges during college years, for both social reasons and for enhancing alertness and opposing sleep.

2. Caffeine withdrawal headaches (tapering by half cup per day may diminish) occur but generally one can get off it. Also irritability and anxiety may occur.

Theophylline pharmacologically is a beta adrenergic stimulant: it is commonly used in asthma as a bronchodilator, and sometimes in congestive heart failure in very high doses (500-750 mg). This can have potentially cause marked stimulation: tea contains a fraction of this amount..

CAFFEINE CONTENT OF VARIOUS DRINKS:

PERSPECTIVE: : Amounts in common drinks.

Coffee contains Caffeine alone e.g. 100 mg

Tea contains Caffeine e.g. 40mg , Theophylline e.g. 1 mg of theophylline (less potent stimulant than caffeine) and Theobromine which is a far less potent stimulant but may have diuretic effects.

A soft cola or pop drink contains e.g. 50 mg Caffeine (12 ounce not 5 ounce like tea or coffee cups) and of course no Cocaine.

AMPLIFICATION:

Effects are additive: a cup of coffee plus 2 cups of tea and an over the counter preparation together may produce toxic effects.

The caffeine content of an average cup of coffee (5 ounce ) is actually variable : range 40 mg -150 mg, of tea range 20-ll0 mg, of soda pops 30 mg to 60 mg

Dosage of caffeine in coffee depends on coffee bean , origin (geography, soil, growing season length), harvest, degree of fine grinding, brew length and method.

Similarly, dosage of caffeine of tea will depend upon the type of tea used, the tea leaf cut, and how long it was brewed.

Dosage of caffeine in soda pops will depend mainly upon the decaffeination extraction process from which it was derived and also on the Kola nut (slight). Soft drinks containing caffeine will show it as an ingredient on the product label and the level of caffeine in a particular brand is consistent from can to can because of strict manufacturing controls.

USING A 5 OUNCE CUP SIZE: some guidelines

Coffee via drip method, with fine ground, in machines e.g.110-150 mg

Percolated coffee 64-124 mg.

Instant coffee 40-108 mg.

Tea 1 min. brew 9 mg -33 mg

5 min. brew 20 mg -50 mg

Instant tea 12 mg -28 mg

Percolated Decaffeinated coffee 2-5 mg

Instant Decaffeinated coffee 2 mg

Decaffeinated soft drinks 0 mg to 0.09mg (virtually none)

(Consumers' Union, FDA, National Coffee Association of the U.S.A., and National Confectioner's Association of the U.S., www. /net-abuse.org/~lizardo/caff.sources.html)

12 0UNCE DRINKS:

Iced tea 22-36 mg

Soft drinks vary greatly:

Jolt 72.0 mg

Sugar-Free Mr. Pibb 58.8 mg

Mountain Dew 54.0 mg

Mello Yello 52.8 mg

TAB 46.8 mg

Coca-Cola 45.6 mg

Diet Coke 45.6 mg

Shasta Cola 44.4 mg

Shasta Cherry Cola 44.4 mg

Shasta Diet Cola 44.4 mg

Shasta Diet Cherry Cola 44.4 mg

Mr. PIBB 40.8 mg

Dr. Pepper 39.6 mg

Big Red 38.4 mg

Sugar-Free Dr. Pepper 39.6 mg

Pepsi-Cola 38.4 mg

Aspen 36.0 mg

Diet Pepsi 36.0 mg

Pepsi Light 36.0 mg

RC Cola 36.0 mg

Diet Rite 36.0 mg

Kick 31.2 mg

Canada Dry Jamaica Cola 30.0 mg

Canada Dry Diet Cola 1.2 mg

[National Soft Drink Association , www. net-abuse.org/~lizardo/caff.sources.html]

THE PROCESS OF DECAFFEINATION

Two basic decaffeination processes are used in the U.S.A :

1. water extraction :

a. coffee beans are steamed and then soaked and then rinsed,

b. caffeine diffuses from the beans into the water,

v. uses no artificial chemicals.

2. direct solvent extraction:

a. direct application of methylene chloride, ethyl acetate or carbon dioxide to the coffee beans

b . coffee beans are then steamed to remove the residual solvent, then dried and roasted.

Methylene chloride may when inhaled be an animal carcinogen but to mice in drinking water was not.

The FDA regards its potential health risk as so low "as to be essentially non-existent" (FDA, 1985).

OVER-THE-COUNTER MEDICATIONS (FDA regulated; based per tablet)

Stimulants
NoDoz tablets 100
Vivarin tablets 200

Pain Relievers
Anacin 32
Excedrin 65
Excedrin P.M. 0
Midol 32
Vanquish 33

Cold Remedies
Coryban-D 30

[FDA's Center for Drugs and Biologics; www. net-abuse.org/~lizardo/caff.sources.html]

SHORT BIBLIOGRAPHY

Sources above include the following websites:
www.vhs.com/caffeine.html,
www. net-abuse.org/~lizardo/caff.sources.html

Barone J J, Roberts H: Human consumption of caffeine. In Caffeine, P B Dews, editor, p 59. Springer-Verlag, New York, 1984.

Benowitz N L: Clinical pharmacology of caffeine. Ann Rev Med 41: 277, 1990.

Benton D : Caffeine: use and abuse . Nurs Stand 1989 ; 44 (3 ): 34-6 .

Bruce MS , Lader, M : Caffeine abstention in the management of anxiety disorders . Psychol Med 19 (1 ): 211-4, 1989.

Cameron O G, Modell J G, Hariharan M: Caffeine and human cerebral blood flow: A positron emission study. Life Sci 47: 1141, 1990.

Carroll ME, Hagen, EW, Asencio, M , Brauer, LH : Behavioral dependence on caffeine and phencyclidine in rhesus monkeys: interactive effects . Pharmacol Biochem Behav 31 (4 ): 927-32, 1988.

Charney D S, Heninger G R, Jatlow P I: Increased anxiogenic effects of caffeine in panic disorder. Arch Gen Psychiatry 42: 233, 1985.

Clementz GL , Dailey, JW : Psychotropic effects of caffeine . Am Fam Physician 37 (5 ): 167-72, 1988.

Conlay LA, Evoniuk, G , Wurtman, RJ : Endogenous adenosine and hemorrhagic shock: effects of caffeine administration or caffeine withdrawal . Proc Natl Acad Sci U S A 85 (12 ): 4483-5, 1988.

Couturier E G, Hering R, Steiner T J: Weekend attacks in migraine patients: Caused by caffeine withdrawal? Cephalalgia 12: 99, 1992.

Diener HC, Dichgans, J, Scholz, E, Geiselhart, S, Gerber, WD , Bille, A : Analgesic-induced chronic headache: long-term results of withdrawal therapy . J Neurol 236 (1 ): 9-14 , 1989.

Dunbar GC, Morgan, DD , Perera, KM : The concurrent use of alcohol, cigarettes and caffeine in British benzodiazepine users as measured by a general population survey . Br J Addict 83 (6 ): 689-94, 1988.

Fennelly M, Galletly D C, Purdie G I: Is caffeine withdrawal the mechanism of postoperative headache? Anesth Analg 72: 449, 1991.

Goldstein A, Kaizer S, Whitby O: Psychotropic effects of caffeine in man. IV. Quantitative and qualitative differences associated with habituation to caffeine. Clin Pharmacol Ther 10: 489, 1969.

Graham K : Reasons for consumption and heavy caffeine use: generalization of a model based on alcohol research . Addict Behav 13 (2 ): 209-14, 1988.

Greden J F: Anxiety and depression associated with caffeinism among psychiatric inpatients. Am J Psychiatry 135: 963, 1978.

Greden, JF , Pomerleau, O. Caffeine-Related Disorders And Nicotine-Related Disorders - in Comprehensive Textbook of Psychiatry Sixth Edition. Williams and Wilkins. Baltimore. 1996

Griffiths R R, Bigelow G E, Liebson I A: Human coffee drinking: Reinforcing and physical dependence producing effects of caffeine. J Pharmacol Exp Ther 239: 416, 1986.

Griffiths RR , Woodson, PP : Caffeine physical dependence: a review of human and laboratory animal studies . Psychopharmacology (Berlin) 94 (4 ): 437-51, 1988.

Griffiths RR, Bigelow, GE , Liebson, IA : Reinforcing effects of caffeine in coffee and capsules . J Exp Anal Behav 52 (2 ): 127-40, 1989.

Griffiths R R, Evans S M, Heishman S J, Preston K L, Sannerud C A, Wolf B, Woodson P P: Low-dose caffeine physical dependence in humans. J Pharmacol Exp Ther 255: 1123, 1990.

Hughes J R, Higgins S T, Bickel W K: Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers. Arch Gen Psychiatry 48: 611, 1991.

Hughes J R, Oliveto A H, Helzer J E, Higgins S T, Bickel W K: Should caffeine abuse, dependence, or withdrawal be added to DSM-IV and ICD-10? Am J Psychiatry 149: 33, 1992.

James JE, Paull, I, Cameron, TE, Miners, JO , Birkett, DJ : Biochemical validation of self-reported caffeine consumption during caffeine fading . J Behav Med 11 (1 ): 15-30, 1988.

Johnson GD, Fatis, M, Sonnek, D , Shawchuck, C : A survey of caffeine use and associated side effects in a college population . J Drug Educ 18 (3 ): 211-20, 1988.

Kirmer DA : Caffeine use and abuse in psychiatric clients . J Psychosoc Nurs Ment Health Serv 26 (11 ): 20-5 , 1988.

Koczapski A, Paredes, J, Kogan, C, Ledwidge, B , Higenbottam, J : Effects of caffeine on behavior of schizophrenic inpatients . Schizophr Bull 15 (2 ): 339-44 , 1989.

Kuribara H, Tadokoro S: Caffeine does not effectively ameliorate, but rather may worsen the ethanol intoxication when assessed by discrete avoidance in mice. Jpn J Pharmacol 59: 393, 1992.

Lee MA, Flegel, P, Greden, JF , Cameron, OG : Anxiogenic effects of caffeine on panic and depressed patients . Am J Psychiatry 145 (5 ): 632-5, 1988.

Lee MA, Flegel, P, Cameron, OG , Greden, JF : Chronic caffeine consumption and the dexamethasone suppression test in depression . Psychiatry Res 24 (1 ): 61-5 , 1988.

Levinson H C, Bick E C: Psychopharmacology of caffeine. In Psychopharmacology in the Practice of Medicine, M D Jarvik, editor, p 451. Appelton-Century-Crofts, New York, 1977.

McGowan JD, Altman, RE , Kanto, WJ : Neonatal withdrawal symptoms after chronic maternal ingestion of caffeine . South Med J 81 (9 ): 1092-4, 1988.

Paul S, Kurunwune B, Biaggioni I; Caffeine withdrawal: Apparent heterologous sensitization to adenosine and prostacyclin actions in human platelets. J Pharmacol Exp Ther 267: 838, 1993.

Russ NW, Sturgis, ET, Malcolm, RJ , Williams, L : Abuse of caffeine in substance abusers [letter] . J Clin Psychiatry 49 (11 ), 1988.

Silverman K, Evans S M, Strain E C, Griffiths R R: Withdrawal syndrome after the double-blind cessation of caffeine consumption. N Engl J Med 327: 1109, 1992.

Snyder S H, Katims J J, Annau Z, Bruns R F, Daly J W: Adenosine receptors and behavioral actions of methylxanthines. Proc Natl Acad Sci USA 78: 3260, 1981.

Stein MB , Uhde, TW : Depersonalization disorder: effects of caffeine and response to pharmacotherapy . Biol Psychiatry; 26 (3 ): 315-20, 1989

Stern KN, Chait, LD , Johanson, CE : Reinforcing and subjective effects of caffeine in normal human volunteers . Psychopharmacology (Berlin) 98 (1 ): 81, 1989.

Winstead D K: Coffee consumption among psychiatric inpatients. Am J Psychiatry, 133: 1447, 1976.