Caffeine (1,3,7-trimethyl-xanthine), the most widely ingested psychoactive substance in the world, is a mild central nervous system stimulant with many physiologic, behavioral, and pathologic effects (Greden 1974; Graham 1978; Victor et al 1981; Gilliland and Bullock 1984; Bruce et al 1986; Benowitz 1990; Höfer and Bättig 1994; Benowitz et al 1995; James 1998; Nehlig 1999; American Psychiatric Association 2000). Daily intake of caffeine for most adults in North America ranges from 200 to 500 mg/day, but up to 30% consume more than 500 mg/day, and perhaps 10% ingest more than 1 g/day (Greden 1974; Graham 1978; Bunker and McWilliams 1979; Garfield 1980; American Psychiatric Association 2000). The source of dietary caffeine is primarily from beverages made from coffee beans, tea leaves, or kola nuts. Caffeine use is associated with cigarette smoking and possibly alcohol and other substance use (American Psychiatric Association 2000).
Neuropsychiatric effects of caffeine vary by dose. Daily intake of 100 mg or more (the amount in an average cup of coffee or 2 cans of cola) can be associated with restlessness, nervousness, excitement, and insomnia (with prolonged sleep latency). Higher doses - particularly with a daily intake of 1 gram or more of caffeine - are more likely to produce significant pathologic effects (Greden 1974; American Psychiatric Association 2000). Daily intake of at least 1 gm (1000 mg) can be associated with anxiety, agitation, insomnia, depression, incoherent thoughts, rambling speech, mania, psychosis, as well as muscle twitching, tremulousness, tremors, and possibly seizures.
Caffeine can exacerbate many psychiatric symptoms, particularly anxiety and agitation, but also aggression (Broderick and Benjamin 2004; Hedges et al 2009). Some patients with attention-deficit disorders may self-medicate with caffeine to help relieve symptoms of difficulty sustaining attention, disorganization, and distraction (Hedges et al 2009). Caffeine is also associated with depression, but it is not clear if depressed patients tend to use (overuse) caffeine in an attempt to counteract some of the vegetative symptoms of depression and/or some of the anticholinergic effects of some psychoactive medications, or if instead caffeine somehow contributes to the development or continuation of depression (Winstead 1976; Broderick and Benjamin 2004). Moreover, caffeine can aggravate psychotic symptoms in schizophrenic patients and can induce psychosis in normal individuals who ingest caffeine at toxic doses (Shaul et al 1984; Tormey and Bruzzi 2001; Broderick and Benjamin 2004; Hedges et al 2009). The risk of developing acute psychosis may be aggravated when caffeine is ingested with alcohol and/or ephedra alkaloids (Tormey and Bruzzi 2001) and in patients who use caffeine alone or in combination with other over-the-counter substances as part of a self-prescribed weight-loss regimen (Shaul et al 1984; Tormey and Bruzzi 2001). Caffeine can also cause insomnia and disrupted sleep, which can contribute to exacerbation of psychiatric symptoms.
Caffeine is very widely used among patients with psychiatric disorders, despite its potential for aggravating or inducing psychiatric symptoms and for interacting with commonly prescribed psychoactive drugs (Kruger 1996; Dratcu et al 2007). At least a quarter of inpatient psychiatry patients abuse caffeine, and such individuals tend to be older, single, and have diagnoses of psychosis (Winstead 1976). Furthermore, the potential impact of caffeine use (or overuse) in treatment-resistant psychiatric patients is often overlooked (Dratcu et al 2007). Anecdotal reports support the benefit of caffeine withdrawal in selected patients with treatment-resistant anxiety disorders, schizophrenia, psychotic depression, and mania.
Lucas and colleagues conducted a double-blind placebo-controlled trial of the behavioral effects of caffeine administration in schizophrenic patients (Lucas et al 1990). They found that caffeine increased arousal and augmented psychotic and manic symptoms in these patients.
In some anecdotal reports of caffeine-induced psychosis, the estimated caffeine consumption approximated 5 g/day (Hedges et al 2009). Withdrawal of caffeine resulted in resolution of paranoia and other psychotic symptoms.
The mechanism of caffeine-induced psychosis is not fully understood. Hedges and colleagues speculate that caffeine-induced psychosis with high doses of caffeine resulted from caffeine-induced adenosine antagonism and elevation in brain levels of dopamine (Hedges et al 2009). Caffeine is a competitive antagonist of adenosine receptors and possibly benzodiazepine receptors, and caffeine also inhibits phosphodiesterase and catecholamine metabolism (Phillis 1989; Hedges et al 2009). Chronic caffeine intake is associated with an increased number of brain adenosine receptors, shifting a subset of brain adenosine receptors to a high-affinity state, and increasing sensitivity to adenosine. Adenosine has both inhibitory and stimulant effects on cyclic adenosine monophosphate (cAMP) formation in brain tissue (Phillis 1989), depending on the type of receptor involved. A1 receptors are high-affinity inhibitory sites, whereas A2 receptors are low-affinity excitatory sites. Methylxanthines, including caffeine, are essentially equipotent antagonists of A1 and A2 receptors.
Prevention of caffeine-attributable psychiatric symptoms is possible by improving clinician awareness and recognition of the role of caffeine in such problems, educating patients on the relationship between caffeine and their symptoms, and encouraging gradual withdrawal and discontinuation of caffeine use in such settings (Kruger 1996; Broderick and Benjamin 2004). Setting limits on caffeine intake (eg, with environmental or administrative controls) may be necessary in some psychiatric treatment facilities.
Note that the caffeine content varies for different beverages and depends in some cases upon how they are prepared (Burg 1975; Gilbert et al 1976; Graham 1978; Bunker and McWilliams 1979; Garfield 1980; Gilliland and Bullock 1984; Sawynok 1995; Nehlig 1999; American Psychiatric Association 2000). For rough approximation purposes, a cup of coffee can be considered to be approximately 100 mg of caffeine and a can of soda 50 mg of caffeine. Because patients often underestimate their total caffeine consumption, a patient-maintained diary of intake can be helpful.