Day # 164: Stimulant Use Disorder
- Marcus Hunt
- Jul 28
- 6 min read
Today we will discuss stimulant use disorder. Although the mechanisms of action and clinical profiles of cocaine and amphetamines differ in some important ways, they share overlapping patterns of intoxication, withdrawal, and chronic consequences. In this post, we’ll cover their history, neurobiology, epidemiology, clinical presentation, and evidence-based treatment strategies for stimulant use disorder.
Today's Content Level: Intermediate
Cocaine and amphetamines are powerful central nervous system stimulants with high abuse potential.
Both substances increase extracellular monoamines—primarily dopamine and norepinephrine—leading to intense euphoria, increased energy, and heightened alertness. These effects drive compulsive use and contribute to the development of stimulant use disorders.
History:
Cocaine: Derived from coca leaves, used ritually in South America for centuries. Isolated in the 1860s, famously endorsed by Freud and used in Coca-Cola until the early 1900s.
Amphetamines: First synthesized in the 1880s, medically promoted for asthma, depression, obesity, ADHD, and wartime fatigue. Methamphetamine (more potent, lipophilic) emerged in WWII and has since fueled waves of epidemics.
Clinical Indications:
Cocaine (Schedule II): The only FDA approved indication for current use is as a topical anesthetic and vasoconstrictor for ENT surgeries.
Amphetamines (Schedule II): Includes dextroamphetamine (e.g., Dexedrine), mixed amphetamine salts (e.g., Adderall), and prodrugs of dextroamphetamine (e.g., lisdexamfetamine). FDA approved indications include ADHD, narcolepsy (promotes wakefulness), obesity (short-term, adjunctive treatment), and moderate to severe binge eating disorder (lisdexamfetamine).
Methylphenidate (Schedule II): Includes methylphenidates (e.g., Ritalin, Methylin, Concerta) and dexmethylphenidates (e.g., Focalin). FDA approved indications mirror those listed for the amphetamines.
Off-label uses for prescription amphetamines and methylphenidate include treatment-resistant depression and apathy/fatigue in select patients (e.g., cancer, post-stroke, TBI, other sleep disorders).
Illicit Use Today:
Cocaine: Cocaine HCl (coke, blow, snow, nose candy) = white powder typically snorted (insufflated) or dissolved and injected via IV. Crack cocaine (crack, rock, base) = solid "rock" crystal that is smoked and inhaled. Freebase cocaine = pure unneutralized base similar to crack that is smoked, largely replaced by crack due to cost.
Methamphetamine: Crystal or glass shards (ice, crystal) is smoked (most common), snorted, injected, or ingested. Powder (crank) is snorted, injected, or smoked.
Abuse of prescription amphetamines or methylphenidate: taken orally or crushed and snorted or injected.
Mechanism of Action:
Cocaine and methylphenidate blocks reuptake of dopamine, norepinephrine, and serotonin, increasing extracellular concentrations of these neurotransmitters in the synaptic cleft.
Amphetamines block reuptake of dopamine, norepinephrine, and serotonin AND increase presynaptic release—especially dopamine and norepinephrine. Meth is longer-acting and particularly neurotoxic.
Result:
Dopamine flood → euphoria, confidence, energy (influences the behavioral reinforcement (aka “reward”) system of the brain.
Then: depletion → crash, cravings, dysphoria.
Diagnostic Criteria 3
Diagnostic criteria for all substance use disorders are the same, characterized by a ≥ 12-month period of problematic substance use that leads to impairment or distress and requires ≥2 additional criteria. See Day #160: Introduction to Substance Use Disorders for complete diagnostic criteria and severity specifiers.
Genetics, environmental influences, and mental health comorbidities contribute to vulnerability.
Prevalence by Age: The prevalence of stimulant abuse and stimulant use disorder (StUD) in Americans varies by substance and age group. Young adults (18-25 yo) are the highest risk group. Across all adult age groups, between 1-4% reported nonmedical use of prescription stimulants, 2-3% reported cocaine use, and 0.3-0.5% reported methamphetamine use in the past year. Among young adults, StUD prevalence was 3.5% for prescription stimulants, 0.6% for methamphetamine, and 0.6% for cocaine.
Gender: Men have higher rates than women.
Genetics and Biology: Genetics, including the impact of one’s environment on gene expression, account for about 50% of a person’s risk. DRD2, DAT1, and COMT polymorphisms are implicated.
Environmental Influences: Areas with high unemployment and poverty, individuals with traumatic experiences, and peer/social influences increase risk (e.g., exposure to drug trade for illicit stimulants; academic or athletic performance pressure for stimulant misuse).
Comorbidities: Include ADHD, depression, PTSD, bipolar disorder, and other substance use disorders. Alcohol, opioids, benzodiazepines, or cannabis may be abused to "balance out" stimulants. Comorbidities may complicate both the course and treatment.
History: Obtain a detailed history (onset, frequency, quantity, last use, forms and routes), prior treatment attempts, periods of sobriety, withdrawal symptoms, impact on daily functioning, social history with triggers, legal obligations, and co-occurring psychiatric or medical conditions. Ask about prescription misuse and illicit use. Ask about injection drug use, overdose history, co-use of other substances. Check the prescription monitoring database if available. Assess for other safety concerns related to use, including IV/IN use, sharing paraphernalia, needle licking, exchanging sex for drugs, body packing/stuffing, or impaired driving. Behaviors such as losing medication, “doctor shopping,” and running out of medication early should alert clinicians of possible misuse. Listen for history of sleep deprivation, paranoia, aggression, or impulsivity.
Screen for polysubstance use, especially alcohol, benzodiazepines, or opioids.
Screening questionnaires: DAST (Drug Abuse Screening Test).
Physical exam:
Intoxication: dilated pupils (mydriasis), tachycardia, hypertension, agitation, hyperthermia, and other signs of recent use (track marks, abscesses, heart murmur, injuries).
Medical/chronic complications of use: HTN, arrhythmias, stroke, seizures, HIV, hepatitis, weight loss, bruxism, nasal septum damage (cocaine), skin-picking, dental decay ("meth mouth").
Labs/Diagnostics:
Urine drug screen →
Cocaine (benzoylecgonine) detectable for ~2–4 days.
Amphetamines detectable for ~1–3 days. Beware of false positives (e.g., bupropion, labetalol, trazodone, aripiprazole, and more).
Liver function tests, complete blood count, renal function.
Infectious disease screening → Hepatitis B/C, HIV, TB, STIs, and other blood-borne pathogens should be evaluated, especially in patients with injection drug use.
Cardiac: ECG + troponins for chest pain or arrhythmia risk.
Symptoms:
Euphoria, energy, talkativeness, decreased appetite, insomnia.
High doses can cause paranoia, hallucinations (especially tactile), aggression, seizures, chest pain, arrhythmias, or stroke.
Dilated pupils (mydriasis), tachycardia, hypertension, and hyperthermia.
Treatment:
Supportive care is the mainstay of treatment including rehydration, correction of electrolyte balance, and treatment of hyperthermia.
Ice baths and cooling blankets may be used for severe hyperthermia.
Benzodiazepines for agitation, seizures, or sympathomimetic toxicity. Antipsychotics may be considered for severe agitation or psychosis.
Avoid beta-blockers alone (unopposed alpha activity) in cocaine-induced chest pain—use benzos ± calcium channel blockers.
Monitoring: Continuous monitoring of vital signs, particularly heart rate, blood pressure, and body temperature. Rule out rhabdomyolysis, MI, stroke, or serotonin syndrome.
Look for possible serotonin syndrome, particularly if taken in an overdose with antidepressants or other serotonergic medications.
Remember that withdrawal symptoms of a drug are usually opposite of its intoxication effects. For example, stimulants are energizing and activating, but withdrawal can → post-intoxication depression or "crash." Withdrawal from stimulants is not life-threatening.
Symptoms:
Fatigue, hypersomnia, anhedonia, depression, increased appetite, cravings, constricted pupils, psychomotor agitation or slowing.
Usually peaks within 1–3 days with mild/moderate use, lasts ~1–2 weeks with chronic/heavy use. Some symptoms (anhedonia) can persist for months.
Treatment:
Supportive treatment: Hydration, electrolyte replacement, nutritional support, provide reassurance.
Watch for suicidality—especially in heavy users or comorbid depression. Severe psychiatric symptoms may warrant hospitalization.
•Effective treatment requires a combination of medical, psychological, and social interventions. A multi-disciplinary team—often including psychiatrists, primary care providers, therapists, social workers, and peer support specialists collaborates to address all aspects of the disorder.
Determine the Appropriate Treatment Setting: Choosing the right level of care depends on substance use severity, comorbid conditions, and prior treatment history. See Day 60: Intro to SUD for a description of each level of care.
Severe cases → inpatient detox, ideally followed by a residential treatment program, aka "rehab."
Mild/moderate cases → outpatient management with close follow-up. If outpatient treatment has failed, consider IOP or PHP.
Regardless of treatment setting, best practice may include random drug screening.
Monitoring for relapse and overdose risk is important in patients with polysubstance use histories.
Psychosocial Interventions:
Individual and/or group therapy should be part of every SUD treatment approach. See Day 60: Intro to SUD for a discussion of interventions that include behavioral therapies, peer support & 12-step programs, and family support resources.
Off-Label Medication Adjuncts:
Unlike opioid or alcohol use disorder, there is no FDA-approved medication for stimulant use disorder. Medications are sometimes use off-label to reduce cravings.
Bupropion + Naltrexone shows promise with modest increase in response rates, particularly in methamphetamine users.
Topiramate, modafinil, mirtazapine: Inconsistent results, may help in select cases, more data in reducing cocaine use.
Antidepressants (other than bupropion) and antipsychotics have no demonstrated consistent benefit outside of treating co-occurring psychosis or depression.
Conclusion
•I hope today's less helped you gain a better understanding of stimulant use disorders. In the upcoming lesson, we will discuss phencyclidine (PCP) abuse.
Resources for today's post include:
Articles referenced above
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