Caffeine and Headache: Exploring the Multifaceted Relationship

Purpose: To explore the multifaceted relationship between caffeine and headache disorders, focusing on its dual role as both an analgesic and a potential trigger and to summarize the mechanisms underlying its anti-nociceptive effects. Method: This narrative review synthesizes evidence from experimental, clinical, and epidemiological studies on caffeine's pharmacological actions, its role in adenosine receptor modulation, and its impact across different headache types, including migraine, hypnic headache, post-dural puncture headache (PDPH), medication-overuse headache (MOH), and caffeine-withdrawal headache. Findings: Caffeine exerts analgesic effects through adenosine receptor antagonism, prostaglandin inhibition, GABA-A modulation, and cholinergic facilitation while also enhancing the efficacy of analgesics such as nonsteroidal anti-inflammatory medications (NSAIDs), acetaminophen, and opioids. In migraine, it demonstrates a dual role, relieving attacks by counteracting adenosine-mediated vasodilation and improving drug absorption yet potentially triggering them when intake is excessive or inconsistent due to mechanisms such as magnesium depletion, diuresis, and sleep disruption. Beyond migraine, caffeine shows therapeutic benefit in hypnic headache and PDPH, but chronic use may contribute to MOH through neuroadaptive changes. Abrupt cessation of caffeine often provokes caffeine-withdrawal headache. Conclusion: Caffeine plays a complex role in headache disorders, acting as both a therapeutic agent and a potential trigger. Its effects depend on dosage, timing, individual susceptibility, and headache subtype. Understanding these mechanisms is essential for guiding clinical recommendations and optimizing caffeine use in headache management.Caffeine plays a complex role in headache disorders, acting as both a therapeutic agent and a potential trigger. In migraine, it demonstrates a dual role, either relieving or triggering. Beyond migraine, caffeine shows therapeutic benefit in hypnic headache, spontaneous intracranial hypotension, and PDPH, but chronic use may exacerbate idiopathic intracranial hypertension and contribute to MOH.