Caffeine-Withdrawal Headache: A Clinical Profile

Multiple components of the A1 adenosine receptor-adenylate cyclase system are regulated in rat cerebral cortex by chronic caffeine ingestion.

“…It is possible that this might account, in part, for the development of tolerance to the physiological effects of caffeine (17,18). Furthermore, abrupt withdrawal of caffeine from animals chronically treated with the drug will expose the sensitized Al adenosine receptor-adenylate cyclase complex to maximal stimulation by endogenous adenosine, leading to increased inhibition of adenylate cyclase and possibly accounting for caffeine withdrawal syndrome described clinically (19)(20)(21).…”

“…Chronic ingestion of caffeine, followed by abrupt cessation of drug intake, leads to a number of symptoms, such as headaches, myalgias, fatigue, and anxiety (19)(20)(21). In an attempt to understand the mechanisms underlying the "caffeine withdrawal syndrome" and the development of tolerance to this drug, we have recently begun to assess changes in the Al adenosine receptor-adenylate cyclase system of rat cerebral cortex following caffeine administration (22).…”

Chronic caffeine ingestion sensitizes the A1 adenosine receptor-adenylate cyclase system in rat cerebral cortex.

“…The caffeine withdrawal syndrome represents but one example of such sensitization to agonists. The syndrome has been recognized clinically for years with the predominant symptom being characteristic headaches (27). The essential feature of the syndrome is that individuals must consume large quantities ofcaffeine (-500 mg = 5 cups of coffee) per day until a tolerance develops and then abruptly stop intake (27).…”

“…The syndrome has been recognized clinically for years with the predominant symptom being characteristic headaches (27). The essential feature of the syndrome is that individuals must consume large quantities ofcaffeine (-500 mg = 5 cups of coffee) per day until a tolerance develops and then abruptly stop intake (27). Symptoms usually develop within 18-20 h. Furthermore, reinstitution of caffeine intake relieves symptoms within a short period of time.…”

“…The "propranolol withdrawal syndrome" has been described clinically (22,23), but the biochemical mechanisms responsible for this syndrome remain a matter of debate (16). A "caffeine withdrawal syndrome" has likewise been described in man with symptoms such as headache, myalgias, fatigue, and anxiety, but the mechanisms responsible for this syndrome remain largely unknown (10,(24)(25)(26)(27). In the present study, we chronically administered caffeine to rats and examined its effects on the AIARadenylate cyclase system in rat cerebral cortex.…”