Caffeine and Substance Use Disorders

Abstract

affeine is the most consumed psychoactive drug in the world. As a psychostimulant, it shows all the pharmacological properties of classical psychostimulants, such as cocaine and amphetamine. Those properties include arousal, motor activation, and reinforcing effects. Nevertheless, those effects are milder for caffeine, which depends on its unique mechanism of action, adenosine receptor antagonism. Classical psychostimulants produce a direct potentiation of central dopaminergic, noradrenergic, and serotoninergic neurotransmission, by acting on catecholamine and serotonin transporters. Caffeine, instead, indirectly activates those and several other ascending neurotransmitter systems (cholinergic, histaminergic, and orexinergic) by removing an inhibitory presynaptic adenosinergic tone, mediated by the effect of endogenous adenosine on adenosine A 1 receptors. Caffeine-induced modulation of the dopaminergic system also depends on postsynaptic mechanisms that depend on assemblies of adenosine and dopamine receptors (A 1 -D 1 and A 2A -D 2 receptor heteromers) (for review see Ref. 1).The same as for classical psychostimulants, the effects of caffeine on the dopaminergic system are largely responsible for its relatively mild motor activating and reinforcing effects.1 However, it has been difficult to definitively show a psychostimulant-like biochemical profile of caffeine in the experimental animal. The hallmark of that profile is a significant increase in the striatal extracellular concentration of dopamine, and this has only been clearly seen in a distinct region of the ventral striatum.1 In this issue, Ferre et al. 2 review recent results that indicate that paraxanthine, the main metabolite of caffeine in man, produces stronger motor activating effects and a more significant striatal dopamine-releasing effect than caffeine. This unique pharmacological profile of paraxanthine depends on an additional selective mechanism, other than adenosine receptor antagonism: inhibition of cGMP-preferring phosphodiesterases. These results open up the possibility that a part of the reinforcing effects of caffeine might depend on paraxanthine, which can reach significant plasma levels upon chronic caffeine intake.The overwhelming caffeine consumption all over the world basically demonstrates its reinforcing effects. Several epidemiological studies indicate that regular caffeine intake creates dependence, which in part depends on withdrawal symptoms. But should we consider caffeine as a drug with potential abuse liability? Researchers and clinicians have been debating about the addictive potential and clinical importance of caffeine use. In this issue, Budney et al.3 present the results of a survey among addiction professionals (members of six clinical/scientific organizations that focus on addiction) about the clinical importance of caffeine withdrawal and dependence. The survey indicates that most professionals believe that caffeine withdrawal and dependence exist and are clinically relevant. However, there was no consensus about t...

Does early exposure to caffeine promote smoking and alcohol use behavior? A prospective analysis of middle school students

“…To the extent that caffeine is experienced as increasingly rewarding, the use of substances to regulate mood in general may be reinforced. This mechanism is particularly concerning for youth who are experimenting with new substances, as caffeine use may potentiate the rewarding effects of the new substance and lead to escalation and chronic problems . In that regard, early caffeine consumption could serve to increase the use of nicotine, alcohol and substances in general .…”

“…Caffeine is a psychostimulant possessing arousal, motor activation and reinforcing properties . Stimulant effects are believed to be a product of the competitive blockade of adenosine receptors both centrally and peripherally .…”

Energy drink use frequency among an international sample of people who use drugs: Associations with other substance use and well-being

“…ED marketing promoting the psychoactive effects of the beverage (Reissig et al, 2009), and iii.) caffeinated ED consumption resulting in 'cross-sensitisation' whereby the dopamine system is primed to respond in a rewarding and reinforcing manner to alcohol and other stimulant drugs (Arria et al, 2014;Ferré, 2013;Temple, 2009). …”

Caffeine and Sleep in Adolescents: A Systematic Review

“…16 Some potential risk factors, such as technology use, have featured heavily in adolescent sleep research during recent years, 17,18 whereas others, such as caffeine use, have been largely neglected. 19 This is despite caffeine being a substance with psychostimulant properties (and thus contraindicated for sleep), 20 excessive consumption of caffeinated products by adolescents, 21 and rapid growth of a number of high-caffeinated food and beverage products available to, and marketed at, adolescents. 22 A new meta-analysis of risk factors associated with adolescent sleep by the authors' group has shown that use of caffeinated products were linked to less sleep in adolescents, whereas using a phone, the Internet, or TV was not.…”