This commentary is to inform clinicians challenged with an increase in people seeking treatment for Substance Use Disorder (SUD), that the ninety percent revolving door, is, in part, due to post–withdrawal, untreated neurotoxicity. This impairment attenuates neurotransmitter signaling and compromises resting state functional connectivity, leading to unwanted sequelae including depression, sleep disturbances, sensation seeking, lack of satisfaction and impulsivity. Neuroimaging studies indicate that neurobiological recovery can take years. Like a “double edge sword” SUD has a biological bi –directional (bio-directional) effect on the brain reward circuitry. The acute intake of psychoactive drugs results in heightened dopaminergic activity, while, the opposite, hypodopaminergia occurs following chronic abuse. Individuals with SUD can have a genetic predisposition, compounded by stress and neurotoxically induced, epigenetic insults that impact recovery from protracted abstinence. Follow-up post –short-term recovery usually includes supportive therapies and programs like 12 –steps and other fellowships. However, relapse will usually occur if post –short-term recovery hypodopaminergia is not treated with attempts at epigenetic manipulation of compromised brain neurochemistry using some manner of pro-dopamine regulation.