Caffeine in Food and Dietary Supplements Examining Safety: Workshop Summary (2014) / Chapter Skim
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6 Caffeine Effects on the Central Nervous System and Behavioral Effects Associated with Caffeine Consumption
6 Caffeine Effects on the Central Nervous System and Behavioral Effects Associated with Caffeine Consumption
Pages 89-128
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From page 89... ...
MECHANISMS OF THE CENTRAL NERVOUS SYSTEM EFFECTS OF CAFFEINE Presented by Sergi Ferré, Ph.D., M.D., National Institute on Drug Abuse Caffeine is a psychostimulant with the same central effects as the classical nervous system psychostimulants cocaine and amphetamine, according to Sergi Ferré. That is, it increases motor activity and has both arousal and reinforcing effects, although its reinforcing effects are not as strong as those of the classical psychostimulants.
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From page 90... ...
O'Brien emphasized the individual variation in the behavioral effects of caffeine exposure and suggested that caffeine addiction may have a genetic basis. • Amelia Arria said the consumption of caffeinated energy drinks was first associated with risk-taking behavior in 1996.
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From page 91... ...
In both cases, the end result is a significant increase of dopamine in the extracellular space, which in turn activates the postsynaptic dopamine D1 and D2 receptors. In contrast to cocaine and amphetamine, in the early 1990s scientists already knew that the main mechanism underlying caffeine psychostimulation was adenosine receptor antagonism.
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From page 92... ...
and paraxanthine, but not theobromine, had the opposite effect; that is, they potentiated locomotor activity of bromocriptine. That finding suggested the existence of an antagonistic interaction between the postsynaptic adenosine A2A and dopamine D2 receptors, through which A2A receptor agonists would behave as D2 receptor antagonists, and A2A receptor antagonists would behave as dopamine as D2 receptor agonists.
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From page 93... ...
. Together, these various elements -- the dendritic spine, the glutamatergic terminal, dopaminergic terminal, and glial processes that wrap around the glutamatergic synapse -- constitute a functional unit known as the striatal spine module, a type of local module.
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From page 94... ...
Other Mechanisms of Caffeine Psychostimulant Effects In Ferré's opinion, scientists have reached a high level of understanding of at least one mechanism of action of caffeine: the A2A-D2 antagonistic interaction mediated by the A2A-D2 receptor heteromer localized in the indirect MSN. The mechanism explains not only the motor-depressant effects of A2A receptor agonists but also the motoractivating effects of caffeine and other A2A receptor antagonists (Orrú et al., 2011)
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From page 95... ...
Two new concepts, "receptor heteromer" and "local module," facilitate the understanding of the functional role of interactions between neurotransmitters and receptor heteromers in the central nervous system and of the mechanisms of caffeine and other central-acting drugs.
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From page 96... ...
Not only does the dosage of caffeine vary widely across sources, with several coffees and energy drinks exceeding the FDA limit for caffeine in cola, but caffeine use patterns vary across the lifespan. Average daily caffeine consumption increases and peaks in the 35- to 54-year-old age group and then tapers off (Frary et al., 2005)
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From page 97... ...
Although the caffeine content of coffee can vary on the basis of how it is brewed and where it is purchased, nonetheless caffeine is a natural component of coffee. Soda and energy drinks do not naturally contain caffeine.
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From page 98... ...
Participants were provided both caffeinated and noncaffeinated versions of the same soda and were evaluated for their willingness to work for each type of soda. After the test, participants were sent home with four 2-liter bottles of either caffeinated or noncaffeinated soda, with participants not knowing which type they had, where they consumed the same amount of soda daily (32 oz)
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From page 99... ...
Temple did not show the data, but she said that there was no change in the reinforcing value of the noncaffeinated soda in either males or females. Nor were any differences observed on the basis of use (stratification)
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In a subsequent study, Temple and her team conducted the same tests on prepubertal versus postpubertal children. They found that, for both heart rate and systolic blood pressure, postpubertal females show dampened responses to caffeine compared to males.
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From page 101... ...
, both the 1 mg of caffeine per kg and the 2 mg of caffeine per kg doses improved the number correct, reaction time, and number correct per minute on the Stroop test and reduced the standard deviation of the Stroop test. In general, according to Temple, caffeine affects cognitive functioning in children.
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From page 102... ...
ADDICTIVE PROPERTIES OF CAFFEINE Presented by Roland R Griffiths, Ph.D., Johns Hopkins University School of Medicine Roland Griffiths provided an overview of the evidence for five human behavioral effects of caffeine: subjective effects, reinforcing effects, tolerance, physical dependence (i.e., withdrawal)
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From page 103... ...
produce predominately dysphoric subjective effects. Reinforcing Effects Reinforcing effects, which refer to the self-administration of caffeine, have been demonstrated very clearly in both laboratory animals (e.g., baboons)
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From page 104... ...
, about 50 percent of individuals who were switched from caffeine to placebo reported moderate or severe headache and about 11 to 12 percent reported substantial increases in depression and fatigue. Individuals switched from caffeine to placebo also demonstrated decreased psychomotor tapping performance and increased unauthorized medication use, mostly for headache.
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From page 105... ...
Addiction: DSM Substance Dependence Syndrome The DSM-5 does not officially recognize caffeine addiction, or dependence syndrome, as a diagnosis, given that too few studies have been completed; they did propose research criteria. Still, Griffiths identified eight studies showing that some people do in fact fulfill DSM-4 or DSM5 criteria for a diagnosis of substance dependence as applied to caffeine: Strain et al.
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From page 106... ...
. Conclusions with Respect to Caffeine Withdrawal and Addiction In Griffiths's opinion, with respect to withdrawal, numerous studies, around 75 percent, indicate that cessation of caffeine consumption after a period of daily intake can result in a distressing withdrawal syndrome involving functional impairment.
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. Caffeine addiction is a less well-established effect than caffeine withdrawal, which is consistent with the DSM-5 committee recommendation that caffeine use disorder be recommended as a diagnosis for further study.
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From page 108... ...
; withdrawal (not counted if prescribed by a physician) ; more use than intended; craving for the substance; unsuccessful efforts to cut down; excessive time spent in acquisition; activities given up because of use; use despite negative effects; failure to fulfill major role obligations; recurrent use in hazardous situations; and continued use despite consistent social or interpersonal problems.
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From page 109... ...
But they did include it in the appendix to stimulate research. O'Brien said, "Most of us are not prepared to say that there is such a thing as caffeine addiction, but there is definitely caffeine withdrawal." According to O'Brien, many committee members resisted adding caffeine withdrawal disorder to DSM-5.
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From page 110... ...
ENERGY DRINK USE AND RISK TAKING DURING ADOLESCENCE AND YOUNG ADULTHOOD Presented by Amelia Arria, Ph.D., University of Maryland, College Park At an FDA public hearing on functional foods on December 5, 2006, Amelia Arria and colleagues submitted remarks on the association between the consumption of highly caffeinated energy drinks and risktaking behavior. At this IOM workshop, Arria discussed additional evidence that has accumulated since that time and that has raised concerns among public health professionals worldwide about the possible contribution of energy drink consumption to risk-taking behavior that ultimately impacts the health and safety of adolescents and young adults.
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From page 111... ...
. Arria noted that the frequency of energy drink use among the studies she was able to locate that specifically focused on risk-taking behavior were studies on college students and that the prevalence estimates of energy drink consumption among that age group are much higher than was alluded to earlier during the workshop discussion.
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From page 112... ...
, with 8.2 percent of nonenergy drink users and 18.8 percent of energy drink users starting to use prescription stimulants the following year (see Figure 6-2)
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NOTE: AOR = adjusted odds ratio. SOURCE: Arria et al., 2010.
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From page 114... ...
A typical finding was that reaction time scores measured 60 minutes after ingesting caffeine improved when tested in a double-blind, placebocontrolled trial, with the caffeinated group showing faster reaction times than the noncaffeinated group (see Figure 6-3)
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From page 115... ...
Reaction time as a function of caffeine exposure (top) and number of targets detected in a sustained attention task as a function of caffeine dose (bottom)
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From page 116... ...
Cholinergic changes are another plausible mechanism to explain the beneficial effects of caffeine, one that does not depend on alertness being low. According to Smith, caffeine has been shown to improve the speed of encoding new information via cholinergic changes, with reaction time to new stimuli decreasing as the caffeine dose increases.
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From page 117... ...
Although these findings tell what Smith said is a "very nice story," he acknowledged that there is an alternative view: that caffeine has no positive effects, that rather it just removes the negative effects of caffeine withdrawal. He referred to earlier workshop discussions on the negative effects of caffeine withdrawal, including headaches, mood changes, and impaired performance (see summaries of Roland Griffiths's and Charles O'Brien's presentations earlier in this chapter)
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From page 118... ...
Until such clarity is reached, there are two plausible mechanisms. Either energy drinks are causing the problems among the school children that he and his colleagues are observing, or energy drink consumption may itself be an outcome, with some other factor driving both energy drink consumption and poor attainment, attendance, and behavior.
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From page 119... ...
When asked how to reconcile the fact that the mechanism of action for caffeine (which acts on adenosine receptors) is very different from the mechanism of action for cocaine (which acts on dopamine receptors)
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From page 120... ...
Temple reiterated that she and her research team have found a greater responsiveness to caffeine among postpubertal males "across the board," that is, not just with cardiovascular effects but also with reinforcing and subjective effects. Blinded Studies of Caffeine Withdrawal Griffiths identified Silverman et al.
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From page 121... ...
In addition, the researchers reported that every individual with a prescribed attention deficit hyperactivity disorder (ADHD) medication was using energy drinks, a finding that suggested to Arria that someone should probably be studying the interaction between energy drinks and medical use of prescription stimulants.
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Withdrawal Suppression Following Smith's presentation, Roland Griffiths commented about withdrawal suppression and the fact that some experts attribute all observed beneficial effects to caffeine withdrawal suppression. "That seems radical," Griffiths said.
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2011. Energy drink consumption and increased risk for al cohol dependence.
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2007. Neurotransmitter receptor heteromers and their integrative role in "lo cal modules": The striatal spine module.
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1998. Physical dependence increases the rela tive reinforcing effects of caffeine versus placebo.
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2013. The impact of alcohol and energy drink consumption on intoxication and risk-taking behavior.
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2009. Caffeine withdrawal, acute effects, tolerance, and absence of net beneficial effects of chronic administration: Cerebral blood flow velocity, quantitative EEG, and subjective effects.
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2012. Associa tions between energy drink consumption and alcohol use behaviors among college students.
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