Headache caused by use of or exposure to a substance, with onset immediately or within hours.
8.1 Headache attributed to use of or exposure to a substance can be caused by a toxic substance, as an unwanted effect of a substance in normal therapeutic use or in experimental studies.
Headache as a side-effect has been recorded with many drugs, often merely reflecting the high prevalence of headache. Only when it occurs more often after an active drug than after placebo in double-blind controlled trials can headache be regarded as a true side-effect. The double-blind design can also be used experimentally to study the relationship between drug effects and headache. In some cases, for example nitric oxide (NO) donors, such studies have led to a deeper understanding of the involvement of neurotransmitter mechanisms in primary headaches.
In general, people with 1. Migraine are much more susceptible to such headaches than other individuals, and the same may be true for people with 2. Tension-type headache or 3.1 Cluster headache. A number of substances, such as NO donors and histamine, induce an immediate headache in both normal volunteers and in migraineurs. However, it is now clear that people who have primary headache disorders also develop a delayed headache, one to several hours after the substance has been cleared from the blood. Knowledge of the potential headache-inducing effects of substances in clinical use is important in order to label these substances appropriately. Combinations such as alcohol and disulfiram may cause headache when individual agents might not.
Paradoxically, the headache encountered by most people after heavy alcohol use may be a positive feature because it encourages avoidance of excessive drinking.
Substances that cause headache through their toxic effects, such as carbon monoxide, cannot be studied experimentally and the causal relationship between exposure and headache has therefore to be demonstrated in clinical cases where the substance has been used accidentally or for suicide attempt.