With the upswing of "chemical imbalance" disorders that surfaced in the latter twentieth century, many researchers frantically attempt to unravel the brain's intricate clockworks. In turn, as the number of persons suffering with mental issues mount, it seems that doctors, pressed for time, are quick to refer patients to psychiatrists. Failing to request a medical physical, many psychiatrists hand out medications, often masking the underlying physical problem. 

People have overlooked two simple but deleterious factors: 1,3,7 trimethylxanthine and allergy. Simply put: caffeine allergy.  It is medical knowledge that the longer a person is exposed to a drug, the higher the chances are for developing a tolerance, and an allergy to the substance. Once this happens, caffeine allergic persons can't properly metabolize caffeine, which is rapidly absorbed by all organs, and distributed into intracellular compartments, and extracellular water. 

Mentioned in a 1936 article by Drs. McManamy and Schube, a young woman, allergic to caffeine, presented with alternating states of delirium and mania, resembling schizophrenia (1). After the recorded case, allergy documentation becomes rare. And not surprisingly.

The drug's stimulating properties masks its allergic symptoms. Circulating adrenaline (epinephrine) increases in caffeine consuming persons (2,3). In its synthetic form, epinephrine is the drug of choice for anaphylactic reactions, halting allergic reactions. But added to a stimulant reaction, excess adrenaline may induce delusions. And the breakdown of some adrenaline byproducts mimics symptoms of schizophrenia (4).

Brain levels increase proportionately with dosage (5). In allergic persons, each cup of coffee, cola, tea, every piece of chocolate, and any ingested caffeine products, intensifies toxic psychosis. Half-life increases. Subsequent doses, including minute amounts, act as a bolus. Cells are poisoned, including neurons.

Symptoms of cerebral allergy can range from minimal reactions, such as lack of comprehension and inability to focus, to severe psychotic states, such as delusions, paranoia, and hallucinations (6). It's known that amphetamine psychosis can't be distinguished from schizophrenia (7,8). With a caffeine allergic person's inability to eliminate, continually ingesting caffeine, neurotransmitter levels, including dopamine and adrenaline, quickly increase. Cells rapidly absorb the drug.

Dopamine increases proportionately to the amount of stress (9). The higher the adrenaline level, the greater the increase in dopamine. Serotonin also increases. Dopamine and serotonin decrease during partial, toxic withdrawal states. But as long as caffeine remains in the toxic body, neurotransmitters never adjust to the victim's natural state. 

Toxicity is known to cause excitement, agitation, restlessness, shifting states of consciousness, and toxic psychosis (10), mimicking amphetamine psychosis. Allergic individuals may be erroneously diagnosed, medicated, and lost in a dark disturbed world, until death.

Adenosine receptors are blocked by caffeine (11,16), maintaining neuronal firing. Persons remain excited and often euphoric.

Caffeine toxicity may be mistaken for bipolar disorder (1,12). Symptoms include: chattiness, repetitive thought and action (resembling obsessive compulsive disorder, OCD), restlessness, psychomotor agitation, alternating moods, anger, impulsiveness, aggression, omnipotence, delirium, buying sprees, lack of sexual inhibition, and loss of values.

Allergy can mimic Attention Deficit Disorder (ADD) (13). As far back as 1902, T. D. Crothers noted that many caffeine consuming children "exhibit precocity" and "functional exaltation" (14). 

Caffeine poisoning may also resemble schizophrenia. One woman's conversational topics wandered from subject to subject. She screamed, and believed that she was in prison. Natural judgement was impaired (1). In 1931, a truck driver brought to the hospital in a confused and irritable condition, complained of being attacked by flies. Flies were never present. Examination revealed that he'd consumed large amounts of cola (15). One gentleman ended his political speech with predictions and threats, out of the ordinary for his personality, stunning the audience (14). Another case describes a man, who imagined himself very wealthy, and assumed that his mental state was normal (14). 

Caffeine toxicity may also masquerade as depression, and anxiety. In 1925, Powers described nervousness, visual problems, and dizziness, in patients he discovered suffered from caffeine toxicity (16). In 1974, caffeine toxic patients, experiencing the same symptoms, were erroneously admitted to a psychiatric hospital, for treatment of anxiety (16,17). In other studies, depression and anxiety are also correlated with caffeine intake (18,19,20,21).

In several reports, patients diagnosed with anxiety disorder experienced panic attacks with ingestion of caffeine (18,19,20). One study reveals that six persons improved with caffeine cessation and remained improved for at least six months (21). Other reports reveal that some persons not afflicted with panic disorder, experienced panic attacks with intravenously administered caffeine (22, 23). 

Written materials on panic disorder symptoms and anaphylactic symptoms do not clearly differentiate between the two. Parasthesia (pins and needle sensations), a feeling of choking, hyperactive symptoms, chest pains, and hyperventilation, amongst other symptoms, are common in both conditions. They're also common in many caffeine consuming persons.

This suggests that caffeine allergy may be responsible for many cases of panic disorder. In which case, panic attacks in allergic individuals are suppressed anaphylactic reactions - mimicking ADHD, and panic disorder. They're "have to get up and run" and "I think I'm losing my mind" feelings, brought about by increased neurotransmitter levels, associated with the "fight or flight" syndrome.

Dr. William Walsh connected anxiety and severe allergic reactions. Dr.Walsh maintains that allergic anxiety stems from a choking sense, and loss of air; not a psychological deficit (24).

Caffeine converts into many byproducts, including theophylline. Theophylline keeps the bronchial tubes open. Allergic individuals are less likely to suffer respiratory collapse, during an anaphylactic reaction. 

A proficient Boston neurologist mentions that sixty-six percent of elevated CPK MM (creatine phosphokinase of muscle) levels are of an "unknown origin" (25). Innumerable mid to late twentieth century studies reveal that a high number of persons diagnosed with mental disorders, including personality disorder, mania, BPD, depression, catatonia, and schizophrenia, exhibit elevated CPK MM levels (26,27,28-38,39,40-50). 

The high majority of these studies, and others, attribute elevated CPK levels to a commonality between patients with mental disorders. Not one focuses on caffeine allergy as a contributing factor of mental disorders.

CPK MM, a muscle enzyme, increases with severe muscle trauma, burns, inflammatory states, and poisoning. This may stem from drugs (36,37,38,39), including cocaine, alcohol, amphetamines, heroin, and stimulants (37,40). Antihistamines, salicylates, cyclic antidepressants, theophylline, and others also cause this disorder (37).

This condition, called rhabdomyolysis, stresses and inflames tissues, including brain cells, breaking down muscle fibers, and discharging potentially toxic cellular matter into the bloodstream (37). Caffeine poisoning can cause rhabdomyolysis (10,37,41).

Myoglobinuria is a symptom of rhabdomyolysis, but often urine myoglobin disappears early in the course of the disorder, or is absent altogether (37). Generalized muscle cramping (associated with rhabdomyolysis) (14,37) may also be absent, or subside early on. Accumulation of caffeine acts as morphine, alleviating pain and discomfort, often inducing muscle rigidity. 

With toxins leaking into the bloodstream, the CPK increases. The higher the CPK, the higher the neurotransmitters, and the deeper into psychosis a person spirals. 

In the late 1960's, Bengzon et al proposed that the leakage of CPK and aldolase might explain schizophrenia (26). Studies on patients with non-restrictive diets, concentrated on various factors, including medication, but failed to include caffeine as a possible factor (26). More recent studies have also overlooked caffeine allergy as a factor in any mental disorders, including schizophrenia. 

A study theorized caffeine as a possible, psychosis inducing agent. Researchers eliminated patients' caffeine for a short duration. It was decided that caffeine aggravates symptoms of thought disorder and psychosis (42). Caffeine was reintroduced-never allowing for sufficient withdrawal times-and significant improvements. 

Proportionate to toxicity, physical withdrawal may take up to 12 months, or longer. Recovery symptoms include memory loss, confusion, tremors, agitated states, insomnia or somnolence, and nightmares associated with amphetamine withdrawal. Following physical recovery, residual mental symptoms, primarily confusion and mood alterations, may exist for several months. 

Evidence suggests that caffeine, and synthetic neurotransmitter altering medications, merely balance one another, and that upon cessation of caffeine, medication is no longer needed. Several reports indicate that upon caffeine cessation, tremors increased in lithium consuming individuals (43). In some patients, caffeine withdrawal increased lithium levels (44). After experiencing a 10-year course of seasonal BPD, a woman eliminated caffeine from her diet. She no longer needed BPD medication (45). 

Caffeine may compete for benzodiazepine receptors (5). In which case, benzodiazepines reduce caffeine's effects and vice versa; balancing each other.

Chronic toxicity may affect functional aspects of every organ (14). Allergic persons may become sensitive to bright light, and resort to sunglasses. It's not uncommon to find dilated but reactive pupils on examination (14). Toxic persons usually present with a whitish, or grayish coated tongue (14, 46). Other findings imply that caffeine inhibits anaphylaxis, by suppressing histamine release (47,48). Due to caffeine's antihistamine properties, a skin test for caffeine allergy may be negative.

Several laboratory tests may be used as markers for allergic toxicity. A detectable  Theophylline level in a patient not receiving Theophylline therapy, and an elevated CPK level are indicative of caffeine toxicity. Along with these, an increased glucose level (10,49) and an elevated white blood count (1,49) may also be significant of toxicity, as many patients assumed afflicted with mental disorders present with elevation of these (1,50). An elevated sedimentation rate, indicative of inflammatory processes, might signify rhabdomyolysis. 

It's highly probable, that millions of consumers developed an allergy to caffeine, especially since availability and production increased rapidly mid- twentieth century. In which case, natural insights, and physical and mental health, have been sacrificed to chronic toxicity, resulting in organic brain, silently posing as ADD, ADHD, anxiety, BPD, depression, OCD, panic, and schizophrenia. Physical ailments resemble amphetamine poisoning, and include drug eruptions, masquerading as "rosacea." 

Back in 1936, McManamy and Schube maintained that in all probability, many people of that era might have already been erroneously diagnosed with some form of mental illness. The doctors further predicted, that in the future, with lack of time, and proper medical insight, many doctors would not be able to diagnose simple disorders such as caffeine allergy, and would label many patients as psychotic (1).

Well, here we are. Welcome to the future. 

(Copyright 2001 © Ruth Whalen M.L.T., ASCP, BA. Tenpaisleypark@hotmail.com Reprinted with permission.)

REFERENCES:
1. McManamy MC, Schube PG. Caffeine Intoxication: Report of a Case the Symptoms of which Amounted to a Psychosis. N Eng Journ Med. 1936. 215:616-620.

2. Cherniske, Stephen. Caffeine Blues: Wake Up to the Hidden Dangers of America's #1 Drug.New York: Warner. 1998. 

3. James, Jack E. Understanding Caffeine: A Biobehavioral Analysis. California: Sage. 1997.

4. Huxley, Aldous. THE DOORS OF PERCEPTION and HEAVEN AND HELL. New York: Harper & Row. 1954.

5. Spiller, Gene A., ed. The Methylxanthines Beverages and Foods: Chemistry, Consumption, and Health Effects. New York: Alan R. Liss Inc. 1984.

6. Sheinken, David, Schachter, Michael, Hutton, Richard. The Food Connection: How the Things You Eat Affect the Way You Feel-And What You Can Do About It. New York: Bobbs-Merrill Co. 1979.

7. Arieti, Silvano. Interpretation of Schizophrenia. New York: Basic Books, Inc. 1974.

8. Lukas, Scott. The Encyclopedia of Psychoactive Drugs: Amphetamines: Danger in the Fast Lane. New York: Chelsea House. 1985.

9. Ruden, Ronald. The Craving Brain. New York: Harper Collins. 1997.

10. Fisher Scientific Corporation. Material Safety Data Sheet: Caffeine. NJ: MDL Information Systems. 1984. (Rev. 1995). 

11. Nehlig, A. Are We Dependent upon Coffee and Caffeine?: A Review on Human and Animal. Neurosci and Biobehav Reviews. 1999. 23:563-576.

12. American Psychiatric Association. Caffeine-Induced Organic Mental Disorder. Diagnostic and Statistical Manual III-R (DSM III-R). 1987 and 1994. http://www.drowning.com/caffeine.html.

13. Rapp, Doris. Is This Your Child?: Discovering and Treating Unrecognized Allergies in Children and Adults. New York: William Morrow & Co. 1991. 

14. Crothers, T.D. Morphinism and Narcomanias from Other Drugs. Philadelphia: W. B. Sanders & Co. 1902.

15. Shen WW, D'Souza TC.Cola-induced psychotic organic brain syndrome: A Case Report. Rocky Mountain Med Journ.1979. 76: 312-313.

16. Snyder SH, Pamela Sklar. PSYCHIATRIC PROGRESS: BEHAVIORAL AND 
MOLECULAR ACTIONS OF CAFFEINE: FOCUS ON ADENOSINE. J. Psychiat. Res.1984. 91-106.

17. Greden JF. Anxiety or Caffeinism: A Diagnostic Dilemma. Amer Journ Psychiatry. 1974. 1089-1092.

18. Lee MA, Flegel P, Greden JF, Cameron OG. Anxiogenic effects of caffeine on panic and depressed patients. American Journ Psychiatry. 1988. 145: 632-635. 

19. Clementz GL, Dailey JW. Psychotropic effects of caffeine. Amer Fam Physician. 1988.37: 167-172. 

20.Boulenger JP, Uhde TW, Wolff EA 3rd, Post RM. Increased sensitivity to caffeine in patients with panic disorders. Preliminary evidence. Arch Gen Psychiatry. 1984. 41:1067-1071.

21. Bruce MS, Lader M. Caffeine abstention in the management of anxiety disorders. Psychol Med. 1989. 19: 211-214.

22. Lin AS, Uhde TW, Slate SO, McCann UD. Effects of intravenous caffeine administered to Healthy males during sleep. Depress Anxiety. 1997. 5: 21-28.

23. Nickell PV, Uhde TW. Dose-response of intravenous caffeine in normal volunteers. Anxiety.1994-1995. 1: 161-168. 

24. Walsh, William E. The Complete Guide to Understanding and Relieving Your Food Allergies. New York: John Wiley & Sons, Inc. 2000. 

25. Neurology Department. New England Medical Center. Boston. 2001.

26. Meltzer, H. Muscle Enzyme Release in the Acute Psychosis. Arch General Psychiatry.1969.21: 102-112.

27. Meltzer, HY. Neuromuscular Abnormalities in the major mental illnesses .I. Serum enzyme studies. Res Publ Assoc Res Nerv Ment Disor. 1975. 54:165-188.

28. Crayton JW, Meltzer HY. Serum creatine phosphokinase activity in psychiatrically hospitalized children. Arch Gen Psychiatry.1976. 33: 679-681.

29. Meltzer, HY. Serum creatine phosphokinase in schizophrenia. Amer Journ Psychiatry.1976. 192-197. 

30. Cohen DJ, Johnson W, Caparulo BK, Young JG. Creatine phosphokinase levels in children with severe developmental disturbances. Arch Gen Psychiatry. 1976. 33: 683-686. 

31. Faulstich ME, Brantley PJ, Barkemeyer CA. Creatine phosphokinase, the MMPI, and Psychosis. Amer Journ Psychiatry. 1984. 141: 584-586.

32. Balaita C, Christodorescu D, Nastase R, Iscrulescu C, Dimian G. The serum creatine-kinase as a biological marker in major depression. Rom Journ Neurol Psychiatry. 1990.28: 127-134. 

33. Swartz CM, Breen KJ. Multiple muscle enzyme release with psychiatric illness. Journ Nerv Ment Disor.1990. 178: 755-759. 

34. Nastase R, Balaita C, Iscrulescu C, Petrea A. The concentration of serum-kinase in manic attacks of primary affective psychoses. Rom Journ Neurol Psychiatry. 1993.31: 97-103. 

35. Blumensohn R, Yoran-Hegesh R, Golubchik P, Mester R, Fluhr H, Hermesh H, Weizman A. Elevated serum creatine kinase activity in adolescent psychiatric inpatients on admission. Int Clinic Psychopharmacol. 1998. 13: 269-272.

36. Berkow, Robert , ed. Sixteenth Edition. The Merck Manual of Diagnosis and Therapy. NJ:Merck Research Laboratories. 1992.

37. Craig, Sandy. Rhabdomyolyis. Emergency Medicine. May, 2001. http://www.emedicine.com/Emerg/topic508.htm. 

38. Davidson, Israel, and Henry John Bernard, eds. Todd-Sanford Clinical Diagnosis by Laboratory Methods. 15th Edition. Philadelphia: W.B. Saunders. 1974.

39. Widmann, Frances K. Clinical Interpretation of Laboratory Tests. Philadelphia: F. A. Davis Co. 1983.

40. Richards, Jr. Rhabdomyolsis and Drugs of Abuse. J Emerg Med. 2000. 
19: 51-56. 

41. Wrenn KD, Oschner I. Rhabdomyolysis induced by caffeine overdose. Ann Emerg Med. 1989. 18: 94-97.

42. Lucas PB, Pickar David, Kelsoe, John, Rapaport Mark, Pato Carlos, Hommer, Daniel. Effects of Acute Administration of Caffeine in Patients with Schizophrenia. 
Biol Psychiatry.1990. 28: 35-40.

43. Jefferson, JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. Journ Clin Psychiatry. 1988. 49: 72-73. 

44. Mester R, Toren P, Mizrachi I, Wolmer L, Karni N, Weizman A.Caffeine withdrawal increases lithium blood levels. Biol Psychiatry. 1995. 37: 348-350.

45. Tondo L, Rudas N. The course of a seasonal bipolar disorder influenced by caffeine.Journ Affect Disor. 1991. 22: 249-251. 

46. Headlee, Raymond, and Wells, Bonnie Corey. Psychiatry in Nursing. New York: Rhinehart & Co. 1948.

47. Shiozaki T, Sugiyama K, Nakazato K, Takeo T. Effects of tea extracts, catechin and caffeine against type-I allergic reaction. Yakugaku Zasshi. 1997. 117: 448-454. 

48. Shin HY, Lee CS, Chae HJ, Kim HR, Baek SH, An NH, Kim MH. Inhibitory effects of anaphylactic shock by caffeine in rats. Int J Immunopharmacol. 2000. 22: 411-418. 

49. Massachusetts Poison Control System. Caffeine. Clinical Toxicology Review. Nov. 1994. http://www.mapoison.org/ctr/9411caffeine.html

50. Hatta K, Takahashi T, Nakamura H, Yamashiro H, Endo H, Fujii S, Fukami G, Masui K, Asukai N, Yonezawa Y. Abnormal physiological conditions in acute schizophrenic patients on emergency admission: dehydration, hypokalemia, leukocytosis and elevated serum muscle enzymes. Eur Arch Psychiatry Clin Neurosci. 1998. 248: 180-188.

Neither the author nor the webmaster has authorized the use of their names or the use of any material contained within in connection with the sale, promotion or advertising of any product or apparatus. Single-copy reproduction for individual, non-commercial use is permitted providing no alterations of content are made, and credit is given.