The effect persists even if caffeine consumption stops, CU-Boulder researchers find.

Many have felt the jitters of too much caffeine, but new evidence suggests that such consumption puts adolescents at risk of suffering those symptoms on a daily basis, even after discontinuing use, according to a University of Colorado Boulder study published in the February edition of the journal Psychoneuroendocrinology.

Some recent studies have found that teenagers or children who consume caffeine have tendencies toward anxiety disorders, “but it’s hard to say whether they are causally related,” said Ryan Bachtell, a professor of psychology and neuroscience, and a member of the CU-Boulder’s Center for Neuroscience.

“The benefit of this type of study is that it can establish more direct links.”

Anxiety disorders are typically characterized by chronic anxiety, or exaggerated worry and tension, even when not warranted by circumstances, and they are linked with major psychiatric disorders.

The study—“Adolescent caffeine consumption increases adulthood anxiety-related behavior and modifies neuroendocrine signaling”—found that adolescent rats subjected to a caffeine regime through drinking water developed behaviors indicating anxiety disorders even after the caffeine was removed, and did so in alarming rates, compared to adolescent rats not subjected to caffeine or adult rats treated similarly.

In addition, researchers found that levels of plasma corticosterone—a stress-related hormone produced by rodents’ adrenal glands—remained high after the caffeine was taken away from the adolescent rats, rising dramatically 24 hours after caffeine drinking was eliminated and persisting for an additional week.

With rising caffeine use by teens and pre-teens, which has been exacerbated by the introduction of energy drinks, such results could raise eyebrows. Recently, studies have linked energy drinks to high blood pressure and arrhythmia, and a student and faculty committee at Vermont’s Middlebury College eliminated campus sales, saying energy drinks promoted poor academic environments and elevated student stress.

“Absolutely one of the things I think is important here is awareness,” Bachtell said. “I don’t think we’re going to ban caffeine—kids have had access to caffeinated sodas for many decades —but what has become the game changer is these energy drinks. Many of them contain a lot of caffeine—and you are talking about a drug that many of us consider to be innocuous, but it can be quite potent in a developing brain.”

The idea for the study began brewing about three years ago, when Bachtell was probing the relationship between adolescent caffeine use and subsequent sensitivity to cocaine use; that study was published last year. It was then CU researchers first began to notice antisocial behaviors in adolescent rats subjected to caffeine.

“If you put two rats together, typically they will have some social interaction—smelling each other or grooming each other,” he said. “What we were originally anticipating was the animal with caffeine would be more aggressive, but they really weren’t interacting at all indicating they may be anxious.”

The current study was led by three CU professors from the Department of Psychology and Neuroscience:

Bachtell, whose lab specializes in the neuropharmacology of drug addiction; Robert Spencer, whose lab specializes in the neurobiological basis of psychological stress and stress adaptation; and Serge Campeau, who specializes in determination of the brain systems responsible for the perception of stress.

What they found almost floored the researchers, as all the evidence lined up almost too perfectly, indicating that the adolescent rats treated with caffeine were showing dysfunction not only in behavioral testing, but also in some hormonal measures.

Testing through 28 days of caffeine consumption, and myriad combinations of test and control cohabitants during the behavioral studies, the animals were also tested for seven days after the removal of caffeine—a “washout” period.

Through all the behavioral and physical testing, the evidence lined up fairly dramatically. Not only were the adolescent rats showing anxiety-related behaviors and elevated basal (minimum) corticosterone levels when treated with caffeine, but they continued to indicate those responses after the drug was removed.

In comparison, adult rats demonstrated much the same behavioral and physical responses while given caffeine, but those behaviors and physical markers disappeared after caffeine was removed.

During the washout period, the corticosterone levels in the test rats actually rose, indicating withdrawal symptoms, but when measured after a mild stressor, their reaction was blunted compared to their control counterparts.

But the real proof of the pudding was in the cellular activity observed in areas of the hypothalamus—a frontal lobe area that links the nervous system to the endocrine system—where such hormonal responses originate.

Increased amounts of a molecular marker for cellular activity, c-fos, indicate that the cells in the hypothalamus are hyperactive, suggesting the creation of an ever-present hormonal response in the caffeinated animals, while it typically becomes more noticeable in control animals only following stress.

“It is important to note (the) … expression was elevated in non-stressed rats that consumed caffeine throughout the adolescent period compared to non-stressed water controls,” the study states.

“These data suggest that caffeine consumption during adolescent development may increase vulnerability to the development of psychiatric disorders. Given the increasing prevalence of caffeine consumption, it is important to enhance awareness of the potentially deleterious long-term effects of caffeine consumption during adolescent development.”

The physical neuroendocrine markers are extremely important, especially as researchers look for pharmaceuticals to fight psychiatric conditions including drug addiction, and extend the findings of Bachtell’s earlier study—“The Effects of Adolescent Caffeine Consumption on Cocaine Sensitivity,” which was published in Neuropsychopharmacolgy last year.

However, according to Dr. Sergi Ferré, a senior principal investigator and chief at the National Institute on Drug Abuse, no less important is how the research helps define the personality changes that adolescent caffeine use may propagate leading to drug abuse—a research interest both he and Bachtell share.

“One of the things we are studying is what are the factors that make us more vulnerable or more resilient to drug abuse (including personality traits),” Ferré said. “These studies in animals suggest that caffeine can modify your personality (cause an increase in the anxiety-personality trait or neuroticism), which makes you more vulnerable to drug addiction.”

Ferré said the the perception that caffeine is an innocuous drug is changing, noting the American Beverage Association is taking a close look at heavily caffeinated drinks. “We can’t absolutely say that because we have these results in rats it is absolutely true for humans, but this should be taken as a warning,” he said.

Jeff Thomas is Lafayette-based freelance writer and a 1983 graduate of the University of Colorado Boulder.