Effect of Uridine on GABA and High Energy Phosphate Levels in Healthy Volunteers
Condition: Healthy Male Subjects
Study type: Interventional
Phase: Phase 1

Summary: 
      On the dual basis of findings indicating GABA increases following acute and eight week
      SSRI/dopamine agonist administration and those indicating GABA-ergic effects following 14 day
      pyrimidine administration, the purpose of this study is to assess our following hypotheses:

        1. Relative to placebo, an oral dose of 1g of uridine BID for seven days will increase
           brain GABA levels in a sample of healthy, unmedicated adult males;

        2. Relative to placebo, an oral dose of 1g of uridine BID for seven days will increase NTP
           levels in a sample of healthy, unmedicated adult males; and

        3. Brain GABA levels will be directly correlated to high energy phosphate levels in this
           sample of healthy, unmedicated adult males.
    

Detailed description: 
      Based on prior MRS studies by our group as well as the work of others, we hypothesize that
      oral administration of uridine will actuate an increase in brain gamma-amino butyric acid
      (GABA) levels, along with beta-nucleotide triphosphate (ß-NTP) levels, as compared with
      baseline. Our aim is to investigate this specific neuropharmacological effect and to
      demonstrate the suitability of a novel magnetic resonance spectroscopy protocol in so doing.
      Our rationale includes the consideration that the clinical utility of an intervention
      demonstrably effective in elevating brain GABA and high energy phosphate levels is broad,
      since lowered GABA and bioenergetic states are associated with a plurality of affective,
      anxiety, and substance use disorders.

      On the dual basis of findings indicating GABA increases following acute and eight week
      SSRI/dopamine agonist administration and those noting GABA-ergic effects of 14 day pyrimidine
      administration, we hypothesize that an oral dose of 2g of uridine per day for seven days will
      increase brain GABA levels in a sample of healthy, unmedicated adult males. We also
      hypothesize that this 2g dose of uridine per day for 7 days will increase ß-NTP levels and,
      further, that the increase in GABA and high energy phosphate levels will be correlated. Of
      note, the phosphorylation of glutamic acid decarboxylase by ATP significantly increased the
      activity of this enzyme, which is reponsable for the synthesis of GABA. This choice of time
      period will allow a determination of time course to efficacy between the acute and extended
      ranges, and further, because therapeutic dosage levels of uridine have yet to be established,
      in this and future studies we hope to determine the optimal dosage at which uridine increases
      brain GABA and ß-NTP levels.
    

Intervention name(s): Uridine
Intervention type(s): Drug
Intervention description(s): 1 gram tablets BID for 7 days
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Keywords: uridine; gamma-amino butyric acid; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Proton Echo-Planar Spectroscopic Imaging