Hypothesizing Balancing Endorphinergic and Glutaminergic Systems to Treat and Prevent Relapse to Reward Deficiency Behaviors: Coupling D-Phenylalanine and N-Acetyl-L-Cysteine (NAC) as a Novel Therapeutic Modality.

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In this hypothesis, we are proposing that the combination of D-Phenylalanine and N-acetyl-L-cysteine (NAC) - two substances that have never been utilized together - is an important advancement to treat Reward Deficiency Syndrome (RDS) [1]. The key motivation for this notion is that the combination will have synergistic attributes to induce dopamine release as well as dopamine stabilization at the brain reward circuitry via different mechanisms. We hypothesize that preferential release of Dopamine, for example, at the Nucleus Accumbens (NAc) along with glutaminergic homeostasis induces not only the release, but also the appropriate regulation of dopamine function that could lead to required “Dopamine Homeostasis.” One way to explain this premise is to review the Brain Reward Cascade (BRC) developed by the one of us (KB) along with Gerald Kozlowski (Blum & Kozlowski 1989) [Figure 1] [1]. The BRC highlights the mechanism in which the proposed D-Phenylalanine and NAC combination works. Open in a separate window Figure 1 Brain Reward Cascade (BRC)