Although reports of caffeine withdrawal in the medical literature date back more than 170 years, the most rigorous experimental investigations of the phenomenon have been conducted only recently. The purpose of this paper is to provide a comprehensive review and analysis of the literature regarding human caffeine withdrawal to empirically validate specific symptoms and signs, and to appraise important features of the syndrome. A literature search identified 57 experimental and 9 survey studies on caffeine withdrawal that met inclusion criteria. The methodological features of each study were examined to assess the validity of the effects. Of 49 symptom categories identified, the following 10 fulfilled validity criteria: headache, fatigue, decreased energy/activeness, decreased alertness, drowsiness, decreased contentedness, depressed mood, difficulty concentrating, irritability, and foggy/not clearheaded. In addition, flu-like symptoms, nausea/vomiting, and muscle pain/stiffness were judged likely to represent valid symptom categories. In experimental studies, the incidence of headache was 50% and the incidence of clinically significant distress or functional impairment was 13%. Typically, onset of symptoms occurred 12–24 h after abstinence, with peak intensity at 20–51 h, and for a duration of 2–9 days. In general, the incidence or severity of symptoms increased with increases in daily dose; abstinence from doses as low as 100 mg/day produced symptoms. Research is reviewed indicating that expectancies are not a prime determinant of caffeine withdrawal and that avoidance of withdrawal symptoms plays a central role in habitual caffeine consumption. The caffeine-withdrawal syndrome has been well characterized and there is sufficient empirical evidence to warrant inclusion of caffeine withdrawal as a disorder in the DSM and revision of diagnostic criteria in the ICD.

A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features.

Although certain commonalities exist between eating and drug use (mood effects, external cue-control of appetites, reinforcement, etc.), it is argued that the vast majority of cases of (self-reported) food craving and food “addiction” should not be viewed as addictive behavior. An explanation is proposed that instead gives a prominent role to the psychological processes of ambivalence and attribution, operating together with normal mechanisms of appetite control, the hedonic effects of certain foods, and socially and culturally determined perceptions of appropriate intakes and uses of those foods. Ambivalence (e.g., “nice but naughty”) about foods such as chocolate arises from the attitude that it is highly palatable but should be eaten with restraint. Attempts to restrict intake, however, cause the desire for chocolate to become more salient, an experience that is then labelled as a craving. This, together with a need to provide a reason for why resisting eating chocolate is difficult and sometimes fails, can, in turn, lead the individual to an explanation in terms of addiction (e.g., “chocoholism”). Moreishness (“causing a desire for more”) occurs during, rather than preceding, an eating episode, and is experienced when the eater attempts to limit consumption before appetite for the food has been sated.

Food Craving and Food “Addiction”: A Critical Review of the Evidence From a Biopsychosocial Perspective

http://physiology.elte.hu/gyakorlat/cikkek/Caffein%20use%20in%20children_what%20we%20know,%20what%20we%20have%20lft%20to%20learn%20and%20why%20we%20should%20worry.pdf

Caffeine use in children: what we know, what we have left to learn, and why we should worry.

Although it is widely believed that caffeine can enhance human performance and mood, the validity of this belief has been questioned, giving rise to debate. The central question is whether superior performance and mood after caffeine represent net benefits, or whether differences between caffeine and control conditions are due to reversal of adverse withdrawal effects. To provide a focussed review of relevant experimental studies with the aim of clarifying current understanding regarding the effects of caffeine on human performance and mood. To avoid the shortcomings of standard placebo-controlled studies, which are ambiguous due to failure to control for the confounding influence of withdrawal reversal, three main experimental approaches have been employed: studies that compare consumers and low/non-consumers, pre-treatment and ad lib consumption studies, and long-term withdrawal studies. Of the three approaches, only long-term withdrawal studies are capable of unambiguously revealing the net effects of caffeine. Overall, there is little evidence of caffeine having beneficial effects on performance or mood under conditions of long-term caffeine use vs abstinence. Although modest acute effects may occur following initial use, tolerance to these effects appears to develop in the context of habitual use of the drug. Appropriately controlled studies show that the effects of caffeine on performance and mood, widely perceived to be net beneficial psychostimulant effects, are almost wholly attributable to reversal of adverse withdrawal effects associated with short periods of abstinence from the drug.

Effects of caffeine on performance and mood: withdrawal reversal is the most plausible explanation.

The psychostimulant properties of caffeine are reviewed and compared with those of prototypical psychostimulants able to cause substance use disorders (SUD). Caffeine produces psychomotor-activating, reinforcing, and arousing effects, which depend on its ability to disinhibit the brake that endogenous adenosine imposes on the ascending dopamine and arousal systems. A model that considers the striatal adenosine A2A-dopamine D2 receptor heteromer as a key modulator of dopamine-dependent striatal functions (reward-oriented behavior and learning of stimulus-reward and reward-response associations) is introduced, which should explain most of the psychomotor and reinforcing effects of caffeine. The model can explain the caffeine-induced rotational behavior in rats with unilateral striatal dopamine denervation and the ability of caffeine to reverse the adipsic-aphagic syndrome in dopamine-deficient rodents. The model can also explain the weaker reinforcing effects and low abuse liability of caffeine, compared with prototypical psychostimulants. Finally, the model can explain the actual major societal dangers of caffeine: the ability of caffeine to potentiate the addictive and toxic effects of drugs of abuse, with the particularly alarming associations of caffeine (as adulterant) with cocaine, amphetamine derivatives, synthetic cathinones, and energy drinks with alcohol, and the higher sensitivity of children and adolescents to the psychostimulant effects of caffeine and its potential to increase vulnerability to SUD. The striatal A2A-D2 receptor heteromer constitutes an unequivocal main pharmacological target of caffeine and provides the main mechanisms by which caffeine potentiates the acute and long-term effects of prototypical psychostimulants.

Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders.

This study examined whether 100 mg caffeine could reinforce preference for the flavour of a novel drink in moderate caffeine users, both after overnight caffeine abstinence and 2 h after receiving 100 mg caffeine, using a two-stage between-groups procedure with 36 volunteers. In the first stage, liking for a test drink (fruit tea) was assessed at breakfast following overnight caffeine abstinence, with half the subjects receiving caffeine. Liking for the tea increased significantly over four trials for subjects receiving caffeine, and decreased significantly in those without caffeine. These effects were greatest in subjects who rated the drink as highly novel. In stage two, subjects evaluated a second drink (fruit-juice) 2 h after receiving the tea, and again half the subjects received caffeine Those subjects who received caffeine in stage two but not stage one showed a significant increase in liking for the fruit-juice over the 4 test days, whereas subjects who did not receive caffeine at either stage showed a progressive decrease in liking for this drink. In contrast, no significant change in liking for the fruit-juice was seen at stage two for subjects who had received caffeine in stage one, regardless of the presence or absence of caffeine at stage two. Caffeine at breakfast increased ratings of energetic and lively, and energetic ratings also increased following caffeine in the fruit-juice in subjects who had not had caffeine at breakfast. Overall, these data are consistent with a negative reinforcement model of caffeine reinforcement, and demonstrate further the utility of the conditioned flavour preference method for evaluating reinforcing effects of drugs in humans.

Hannah Spetch

Papers

Conditioned flavour preference negatively reinforced by caffeine in human volunteers