Dose-response effects of intravenous caffeine in normal volunteers

The administration of caffeine has been developed as a chemical model for the study of anxiety. However, previous researchers investigating caffeine-induced anxiety states in humans have administered oral caffeine. In this dose-response study, we investigated the effects of blindly administered intravenous caffeine (3, 5, and 7 mg/kg) versus placebo in normal control subjects. We report the first series of subjects experiencing olfactory hallucinations (10 of 10 subjects, 24 of 30 infusions) immediately following intravenous caffeine infusion. In addition, consistent with our previous work with oral caffeine, we found dose-related increases in ratings of anxiety and blood levels of cortisol and lactate. One subject experienced a DSM-III-R panic attack. Further questioning revealed that his mother suffers panic attacks. Our findings of olfactory hallucinations are discussed within the context of localized limbic system dysfunction, noting the phenomenologic and possible neuroanatomic overlap between panic disorder and complex partial seizures.