Written by Elizabeth Cairns, Mobilize Recovery Special Projects and Michael Masiowski, MD, reviewed by Code Recover Clinician Advisors, August 2026

Dr. Phillip Moschella talks about his program at Prisma Health and why addiction is a disease of the brain

Addiction, or substance use disorder (SUD), is understood as a chronically relapsing brain disorder driven by progressive neuroadaptations across three interconnected neurocircuits, each corresponding to a distinct stage of the addiction cycle: binge/intoxication (basal ganglia), withdrawal/negative affect (extended amygdala), and preoccupation/anticipation (prefrontal cortex).(source)

These neurobiological changes, and their clinical implications, explain exactly why SUD requires specialized medical and psychological intervention rather than willpower alone:

• Hijacked Reward Circuitry: Addictive substances bypass the brain's natural survival rewards by flooding the nucleus accumbens with dopamine. Over time, the brain downregulates its natural dopamine receptors to compensate (source), making everyday activities feel flat while cementing compulsive drug-seeking behavior.
• Impaired Executive Control: Long-term use weakens the prefrontal cortex—the brain's command center for impulse control and decision-making (source). This physical adaptation explains why an individual sincerely motivated to quit can still experience intense cravings that override conscious resolve.
• Persistent Relapse Vulnerability: Enduring changes in stress and motivation systems remain long after an individual has stopped using (source). This neuroadaptation explains why individuals remain vulnerable to conditioned cues (people, places, or emotions) that trigger severe cravings, sometimes years into recovery.
• Development of Targeted Therapeutics: This biological understanding has facilitated evidence-based treatments — naloxone for opioid overdoses, buprenorphine and methadone to normalize receptor activity, and behavioral therapies that actively work to recalibrate and strengthen prefrontal cortex function (source).

Understanding this model reframes what clinicians see in the ED. A patient who signs out AMA 45 minutes after a naloxone reversal isn't behaving irrationally; their extended amygdala is driving a genuine physiological alarm state. A patient who relapses after a period of stability hasn't failed treatment; a neuroadaptation formed over months or years of use doesn't resolve on a linear timeline. Treating SUD as a chronic, relapsing brain disease, rather than an acute event with a single "fix," is what allows the care team to respond with the same clinical patience given to any other chronic condition.

Co-Occurring Conditions

OUD rarely presents in isolation. Roughly a third of patients have co-occurring depression, and a similar share have an anxiety disorder. (source) Overall, about two-thirds of adults with OUD meet criteria for some form of mental illness. (source) Polysubstance use is also common — most patients with OUD have at least one other current or past substance use disorder, most often involving alcohol, cannabis, or cocaine. (source)

This complexity doesn't change the core protocol — a patient in withdrawal or post-overdose still needs the same rapid assessment, MOUD induction, and peer connection regardless of what else is going on. But it's useful context for why some patients respond less predictably to a straightforward handoff, and why a peer or clinician noticing signs of an underlying psychiatric condition is worth a note to the receiving provider, not a separate intervention in the ED.