Editorial Director, Addiction & Recovery · Last reviewed January 2025
Stimulant use disorder encompasses a spectrum of conditions involving compulsive use of stimulant substances — most prominently cocaine and methamphetamine, and to a lesser extent prescription stimulants. The 2021 NSDUH found approximately 1.9 million Americans had cocaine use disorder and approximately 1.5 million had methamphetamine use disorder. Stimulant-involved overdose deaths have risen dramatically in recent years, particularly when stimulants are combined with opioids.
Neurobiology: Dopamine and the Reward System
Both cocaine and methamphetamine act primarily through dopaminergic mechanisms. Cocaine blocks dopamine reuptake, flooding the synapse with dopamine and producing intense, brief euphoria (15–30 minutes for smoked/injected cocaine). Methamphetamine both blocks dopamine reuptake and causes active release of dopamine stores, producing a more sustained but eventually more neurotoxic effect. With chronic use, both produce dopamine receptor downregulation and dopaminergic neuron damage — the neurobiological basis for the profound anhedonia and depression of stimulant withdrawal.
Medical and Psychiatric Consequences
Cocaine's cardiovascular effects are particularly dangerous: vasoconstriction, tachycardia, and hypertension increase risk for myocardial infarction, stroke, and aortic dissection even in young users without prior cardiovascular disease. Cocaine-induced chest pain is one of the most common emergency department presentations related to stimulant use.
Methamphetamine's neurotoxic effects on dopaminergic and serotonergic neurons produce lasting cognitive deficits — impaired memory, executive function, and processing speed — that may persist for months to years of abstinence, though partial recovery occurs with sustained sobriety. Methamphetamine-induced psychosis (paranoid delusions, auditory hallucinations) affects a significant minority of regular users and can be clinically indistinguishable from primary psychosis during the acute episode.
Stimulant Withdrawal
Stimulant withdrawal, while not medically dangerous, is intensely uncomfortable. The crash following cocaine binge use involves fatigue, depression, increased appetite, and hypersomnia. Methamphetamine withdrawal produces a more prolonged depressive syndrome — profound fatigue, anhedonia, hyperphagia, and hypersomnia lasting days to weeks, followed by months of dysphoria, cognitive impairment, and craving as dopaminergic function gradually recovers.
Treatment
There are currently no FDA-approved medications for stimulant use disorder, though multiple candidates are in clinical trials. CBT with a relapse prevention focus and Contingency Management (CM) — using voucher or prize incentives to reward drug-negative urine screens — have the strongest evidence bases. A meta-analysis of CM for stimulant disorders found it significantly superior to control conditions for abstinence outcomes. The Matrix Model, a 16-week structured outpatient program developed specifically for stimulant use disorders, incorporates CBT, family education, and 12-step involvement with positive evidence.
Related: Cocaine & Mental Health · Meth & Mental Health · ADHD & Substance Use