There is a shortage of clinical studies examining the efficacy of Nicotinamide Adenine Dinucleotide and Enkephalinase infusions (IV1114589NAD) in treating Substance Use Disorder (SUD). This pilot study provides significant evidence that NAD infusions are beneficial in the treatment of SUD...This investigation serves as a rationale to extend these findings onto future research investigating the use of NAD/NADH as a stand-alone treatment...A significant reduction in cravings, anxiety, and depression followed a dose-dependent linear trend. Linear trend analyses showed a significant relationship between NAD infusions and decreasing scores for cravings (P=0.015), anxiety (P=0.003), and depression (P=8.74E- 5). A urine analysis was conducted on a subset of 40 patients midway through the study to assess relapse; 100% of the urine samples analyzed failed to detect illicit substance use.