Cerebral blood flow changes in man by wake‐promoting drug, modafinil: a randomized double blind study

Summary To investigate the effects of a wake‐promoting drug, modafinil on regional cerebral blood flow (rCBF) in healthy volunteers, we performed 99m Tc‐ethylcysteinate dimer single photon emission computed tomography (SPECT) before and after modafinil or placebo administration. Twenty‐one healthy subjects received single doses of 400 mg modafinil or placebo in a double blind randomized crossover study design. Administrations of modafinil or placebo in a subject were separated by a 2‐week washout. Brain SPECT was performed twice before and 3 h after modafinil or placebo administration. For statistical parametric mapping analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 12‐mm full width at half‐maximum Gaussian kernel. The paired t ‐test was used to compare pre‐ versus post‐modafinil and pre‐ versus post‐placebo SPECT images. Differences in rCBF between post‐modafinil and post‐placebo conditions were also tested. Modafinil decreased Epworth and Stanford sleepiness scales whereas placebo did not. The post‐modafinil condition was associated with increased rCBF in bilateral thalami and dorsal pons, whereas the post‐placebo condition showed increased rCBF in a smaller area of the dorsal pons when compared with the drug naïve baseline condition. Compared with the post‐placebo condition, the post‐modafinil condition showed higher rCBF in bilateral frontopolar, orbitofrontal, superior frontal, middle frontal gyri, short insular gyri, left cingulate gyrus, left middle/inferior temporal gyri, left parahippocampal gyrus, and left pons. In healthy volunteers, modafinil increased wakefulness and rCBF in the arousal‐related systems and in brain areas related to emotion and executive function.