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These are headaches that occur in close temporal relation to substance exposure or substance withdrawal. They resolve when the culprit substance is no longer used.


  1. Many substances can cause headaches acutely, with long-term use, or after their withdrawal.

    1. Acute exposure

      1. Nitrites (“hot dog headache”)

      2. Carbon monoxide

    2. Long-term exposure (analgesics)

    3. Withdrawal from acute exposure (alcohol)

    4. Withdrawal from chronic exposure

      1. Caffeine

      2. Opioids

      3. Multiple other medications including estrogen, corticosteroids, tricyclic antidepressants, selective serotonin reuptake inhibitors, and NSAIDs.

  2. Of these headaches, caffeine withdrawal, hangovers, and carbon monoxide poisoning are probably the most common or important causes of morning headaches.


  1. Medication overuse headaches

    1. Headache occurring on 15 or more days per month as a consequence of overusing a headache medication for more than 3 months.

    2. Headaches usually resolve when the medication overuse is stopped.

  2. Caffeine withdrawal headaches

    1. The IHS criteria require that:

      1. Patients drink ≥ 200 mg of caffeine daily for > 2 weeks.

      2. The headaches occur within 24 hours of the last caffeine intake and are relieved within 1 hour by 100 mg of caffeine.

      3. That the headache resolves within 7 days of total caffeine withdrawal.

    2. An average cup of coffee contains about 100 mg of caffeine.

    3. Premium coffees may contain significantly more. A 12-oz (tall) coffee at Starbucks contains 260 mg of caffeine.

    4. The average adult American ingests approximately 280 mg of caffeine each day.

    5. Caffeine withdrawal should be suspected if headaches seem to occur when coffee intake changes, such as on weekends and during vacations.

  3. image Caffeine withdrawal should be considered when headaches occur when patients sleep later than usual or occur mainly on weekends or vacations.

  4. Carbon monoxide poisoning

    1. Presentation runs the spectrum from mild headache to headache with nausea, vomiting, and anxiety to coma and cardiovascular collapse.

    2. Historical features that increase the suspicion of this diagnosis.

      1. A patient’s headache only occurs in a single location and resolves when the patient is removed from this setting.

      2. Multiple people in same setting (family members, roommates) have similar symptoms.

      3. Carbon monoxide poisoning is most common in the winter.

    3. An elevated carboxyhemoglobin level makes the diagnosis. Routine arterial blood gas measurements and pulse oximetry do not detect carbon monoxide poisoning.

  5. image Because carbon monoxide poisoning is potentially life-threatening, the diagnosis should be considered whenever a patient has a potentially consistent history.


  1. Treatment of headaches associated with substances or their withdrawal depends on the substance.

  2. Patients with headaches from carbon monoxide poisoning should be removed from their house while the source is repaired.

  3. Patients with caffeine withdrawal headaches should either be weaned off caffeine or counseled on the need to continue regular use (an option generally preferred by medical students).

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