We examine the relationship between substance use disorder (SUD) and schizophrenia, emphasizing the role of dopaminergic neurotransmission and genetic predispositions within the context of Reward Deficiency Syndrome (RDS). Our hypothesis posits that a deficiency in gamma-type endorphins leads to persistent hyperdopaminergic activity, amplifying schizophrenia-related symptoms such as hallucinations. Thus, alcohol use may function as a physiological self-healing mechanism by increasing gamma-endorphin levels, thereby mitigating dopaminergic hyperactivity. Additionally, we propose that the DRD2 Taq1 A2 allele could offer protection against SUD in certain individuals with schizophrenia, whereas the Taq1 A1 allele may heighten susceptibility to SUD due to impaired dopaminergic reward processing. The proposed dual genetic pathways arise from the independent yet interrelated genetic bases of SUD and schizophrenia, both involving the dopamine system. Epidemiological studies reveal that psychiatric comorbidity correlates with heightened psychopathology, risky behaviors, and diminished psychosocial performance. Further advanced research, including neuroimaging, genome-wide association studies (GWAS), and epigenetic analyses, is needed to unravel the dopaminergic mechanisms underlying SUD and schizophrenia. Understanding these genetic links may pave the way for precise interventions tailored to specific subpopulations. The findings extend the conceptualization of RDS as a framework for understanding psychiatric and addictive disorders, reinforcing the critical role of dopamine dysregulation in their etiology.