BOSTON – Most people just get a mild buzz from their morning coffee, but an unfortunate few have reactions to caffeine ranging from severe agitation to paranoid delusions and psychosis, forensic psychiatrists reported in a poster presented at the annual meeting of the American Academy of Psychiatry in the Law.

Caffeine is known to act as an antagonist of the adenosine A2a receptor, thereby causing an increase in dopaminergic neurotransmission, especially in areas of the brain rich in D2 receptors. "This mechanism may cause or exacerbate psychotic symptoms, and is also triggered by modulation of transmission in the mesolimbic dopaminergic pathways," wrote Dr. Christopher M. Davidson of the University of South Dakota Sanford School of Medicine, Sioux Falls, and his associates.

Caffeine is metabolized by the cytochrome P450 1A2 enzyme. Polymorphisms in the enzyme might affect how individuals metabolize and respond to caffeine, the authors said.

They reported on a forensic case and two corrections cases of caffeine-induced mental and behavioral problems.

In the forensics case, a 24-year old man with no history of mental illness assaulted an emergency room nurse after he had driven all night and ingested the caffeine equivalent of about three cups of coffee, said coauthor Dr. James B. Reynolds of the Northwest Missouri Psychiatric Rehabilitation Center, St. Joseph, in an interview.

The patient had been brought to the emergency department by police whom he had sought out when he began experiencing confusion and paranoia. At one point, without apparent provocation, he jumped out of bed, grabbed the nurse, and shouted: "Why do you do that to me, why do you do that to me?" and cut her neck with a box cutter in his possession.

He was charged with first-degree assault, but was found to have no apparent motive for the assault, no criminal or mental health history, and no evidence of drug or alcohol abuse. He did, however, have a box of caffeine pills in his possession, leading to the conclusion that he was likely suffering from pathologic intoxication.

Dr. Reynolds said that if intoxication occurs because of unforeseeable circumstances, it might qualify as a valid defense against a criminal charge.

Given the circumstances, the prosecutor agreed with the defense, and the man was found not guilty by reason of insanity.

"He came into my hospital, and for nearly 3 years this man was under our observation, and never had one symptom of mental illness and no repeat episode," Dr. Reynolds said.

In the first of the two corrections cases, a 22-year-old man who had been diagnosed with schizophrenia of the catatonic type was living in a section for mentally ill prisoners. He developed new symptoms of activation, irritability, confrontation, restlessness, and high energy with little need for sleep. The episodes occurred at intervals of 1-2 weeks and lasted for 1-3 days.