Conditions: AOD Effects and Consequences
Keywords: GABA glutamate glutamine spectroscopy brain imaging alprazolam dextroamphetamine placebo
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 7
Healthy volunteers: yes

Brief summary:
An advanced technique for rapid magnetic resonance proton spectroscopic imaging (1H-MRSI) will be employed in a drug challenge study in healthy volunteers to spatially map and measure acute changes in the brain chemicals GABA, glutamate and glutamine after administration of a drug. Three condition will be tested in a double-blind fashion, i)depressant, ii)stimulant, iii)placebo. It is hypothesized that unique and reproducible spatial and directional metabolic response patterns will be observed, unique to each condition within the brain.

Detailed description:
Proton magnetic resonance spectroscopy (1H MRS) is a powerful tool for assessing neurochemistry non-invasively in vivo. However, the primary shortcoming in most studies is the lack of spatial coverage afforded by the typical single-voxel design. Limits on participant tolerance and financial resources restrict single-voxel studies to an examination of one or two carefully chosen voxels per scan, thus inadequately addressing the question of focal vs. global pathophysiology. A secondary shortcoming is that most studies report on either GABA or glutamate-glutamine (Glu-Gln) due to the technically demanding spectral-editing techniques that must be implemented in order to resolve and quantify those metabolites with any accuracy.

1H MRS imaging (MRSI) can partially overcome these limitations by providing a global picture of brain chemistry rather than just the focal snapshot afforded by the single-voxel design. However, the scan time necessary for collecting enough data for adequate spatial resolution and signal-to-noise, particularly if also using specialized spectral-editing techniques, is still too lengthy. We recently developed a method that combines Spectroscopic Imaging with the MEGAPRESS-based difference-editing acquisition for optimal GABA detection as well as for optimal detection of Glu and Gln. This MEGACSI sequence will permit us to obtain the maximum amount of neurochemical information in a clinically sound scan time, while using the current state-of-the-art MRS editing methods for optimal detection of GABA, Glu, and Gln.

Arms:
arm 1: Alprazolam (Xanax), gel-capsule, 1mg, single-dose, 1-day arm 2: Dextroamphetamine (Dexedrine), gel-capsule, 20mg, single-dose, 1-day arm 3: Placebo gel-capsule, single-dose, 1-day

Interventions: intervention 1: Alprazolam intervention 2: Dextroamphetamine intervention 3: Placebo
Intervention descriptions: intervention 1: Alprazolam, gel-capsule, 1mg, single-dose, 1-day intervention 2: Dextroamphetamine, gel-capsule, 20mg, single-dose, 1-day intervention 3: Placebo, gel-capsule, single-dose, 1-day

Protocol document: