1. Acute Intravenous Synaptamine Patient 1 “Before”

2. Acute Intravenous Synaptamine Patient 1 “After”

3. Acute Intravenous Synaptamine Patient 2 “Before”

4. Acute Intravenous Synaptamine Patient 2 “After”

5. qEEG STUDIES Subject 1.1: Baseline EEG (Fiq. 1) Baseline EEG analyses shows increased widespread theta (4-8hz) and increased frontal beta (12-25hz) compared to the norm. Widespread increased theta is associated with metabolic disturbance/dysregulation and increased frontal beta is associated with mood disturbance, over-arousal, and anxiety. These features are often associated with anxious, obsessive behaviors, anger, and difficulty de-escalating when upset.

6. qEEG STUDIES Subject 1.1: Post Amino Acid EEG (Fig. 2) Post EEG analyses shows decreased frontal theta (4-8hz) and decreased frontal beta (12-15hz) indicating improved functioning immediately post amino acid intravenous treatment. When individual frequencies are reviewed changes are noted in more detail compared to the norm.

7. qEEG STUDIES BEFORE AFTER

8. qEEG STUDIES Subject 1.2: Baseline EEG (Fig. 3) Note increased widespread theta from 4-7 Hz and increased frontal/central beta at 15-16 Hz.

9. qEEG STUDIES Subject 1.2: Post Amino Acid EEG (Fig. 4) Post intravenous amino acid treatment decreased widespread theta at 4-7 Hz and at 15-16 Hz indicating improved functioning. Subject 2: 24 year old male with a history of opiate addiction. Subject was medication and drug free for 30 days prior to the study. Labeling: Subject 2.1 is pre treatment assessment. Subject 2.2 is post treatment of Subject 2.

10. qEEG STUDIES BEFORE AFTER

11. Oral Synaptamine a. P-Values Group 1 vs. Group 2: Week 1 b. P-Values Group 1 vs. Group 2: Week 2

13. NEUROIMAGING STUDIES Resting–State fMRI After One Dose Synaptamine (n=5) Placebo (n=5)