This study evaluated the effects of a putative activator of brain reward circuitry on outcomes in a 1 -y prospective comprehensive outpatient clinical program. As part of the Gene Narcotic Attenuation Program, Haveos (Synaptamine)™ was administered for the treatment of substance use disorder. Seventy-six patients (45 males and 31 females; mean age, 33 y [standard deviation, 7.0]) who had been given a diagnosis of serious substance use disorder were recruited. After exclusion of 15 patients who dropped out before the end of the study, self-reported craving decreased from program entrance to 12 wk (visual analog scale whereby 0 represents no craving and 5, the strongest craving) for 61 compliant patients (mean decrease, 2.85, 95% confidence interval [Cl], 2.65, 3.05); this improvement was significant (P < .001). Building up to relapse scores (each of 5 individual items and summary value) showed similar improvement after 1 y of treatment; the mean decrease in scores was significant for stress (t=3.3; P=.002), depression (t=4.0; P < .001), anger (t=4.4; P < .001), anxiety (t=4.5, P < .001), drug craving (t=5.4, P < .001), and summary building up to relapse (t=4.1; P < .001). Also, recovery score measures of energy level (t=8.4; P < .001) and ability to refrain from drug-seeking behavior (t=7.4; P < .001) showed significant mean increases from entry to 1 y. During the study, the alcoholic dropout rate was only 7% (4 of 57), which was significantly (Fisher's exact test, P < .001) lower than the 73% (11 of 15) dropout rate reported for psychostimulant users. Although these results are significant, any interpretation must await the performance of rigorous double-blind studies.