Amphetamine Use Disorder

Amphetamine use disorder (AUD) is a condition characterized by pathologic use of psychostimulants. Amphetamines produce their effect by increasing the release and blocking the reuptake of neurotransmitters (dopamine, norepinephrine, serotonin). Medically, they are used for the treatment of ADHD and narcolepsy. Methamphetamines and so-called designer drugs have no clinical use. Intoxication results in euphoria, pupillary dilation, hypertension, skin excoriation, paranoia, and severe aggression. Fatal complications can arise from myocardial infarction and coma. The prognosis for AUD is poor, as there is no FDA-approved pharmacotherapy, but psychosocial interventions have been associated with improved outcomes.

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Definition and Epidemiology


Amphetamine use disorder (AUD) is defined as the chronic (> 12 months) maladaptive use of amphetamines or other stimulants.

  • Most common substances used: prescription pills such as dextroamphetamine and recreational drugs such as methamphetamines and methylenedioxymethamphetamine (MDMA)
  • Intoxication: 
    • Increased energy and euphoria
    • Psychomotor agitation, aggression 
    • Stimulant-induced psychotic disorders and delirium may also occur.
  • Withdrawal: 
    • Development of a substance-specific syndrome due to the cessation (or reduction) of substance use
    • Patients experience physical (nausea, diarrhea, chills, and body aches) and/or psychological symptoms (craving or perceived need to use the substance). 
  • Tolerance: 
    • The need to increase the dose of the substance to achieve desired effect (diminished effect if using the same amount of the substance)


  • Men and women are equally affected by AUD. 
  • Amphetamine-type stimulants rank as the 2nd most widely used illicit substance, behind marijuana. 
  • Creates major public health and law enforcement problems secondary to consumption


Types of amphetamines

  • Classical amphetamines: 
    • Dextroamphetamine, methylphenidate, and methamphetamine
    • Detected in routine urine drug screening (false positive results may occur with the use of pseudoephedrine, bupropion, or beta-blockers)
  • Nonclassical amphetamines: chemically categorized as amphetamines, but clinically considered to be hallucinogens
    • Substituted amphetamines or “designer” drugs: 
      • Includes MDMA (“ecstasy” or “party drug”)
      • Not detected by urine drug screening
    • Bath salts:
      • Synthetic cathinones (large family of amphetamine analogs) 
      • Mechanism of action is similar to that of amphetamines.
      • Prolonged duration of effect (days to weeks)
      • Not detected in urine drug screening

Pharmacological properties

  • Classical amphetamines: block reuptake and facilitate the release of catecholamines, such as dopamine and norepinephrine
  • Nonclassical amphetamines: same effect as classical amphetamines, plus serotonin release
  • Rapid oral absorption and rapid onset of action
  • Most common routes of administration:
    • Smoking (68%)
    • Snorting (31%) 
    • IV injection for faster activation

Clinical Presentation and Diagnosis

The diagnosis of amphetamine intoxication and withdrawal is made based on the symptoms, taking a history of consumption, and urine drug screening.

Amphetamine intoxication

  • General: hyperactivity, euphoria, dry mouth (leading to tooth decay), agitation, psychosis
  • CNS: hyperreflexia, seizures
  • Cardiovascular system: ↑ blood pressure, tachycardia, arrhythmia  
  • GI: nausea, ischemic colitis 
  • Musculoskeletal: skin excoriation, bruxism (teeth grinding) 
  • Ophthalmologic: pupillary dilation

Amphetamine withdrawal

  • Important to obtain detailed history of amphetamine use, including most recent use 
  • General: malaise, disturbed sleep, irritability
  • CNS: fatigue, headaches, tremors
  • GI: hunger
  • Ophthalmologic: constricted pupils  
  • Patient enters a state of severe depression after intoxication (“crash” phase). 
  • Withdrawal is not life-threatening; however, patients may develop suicidal ideation.

Management and Complications

Amphetamine intoxication

Controlling agitation and sympathetic overactivity are the main steps in management. The approach to amphetamine intoxication includes:

  • General measures:
    • Rehydrate.
    • Correct electrolytes. 
    • Treat hyperthermia (aggressive sedation, neuromuscular paralysis, and fluid resuscitation).
    • Treat sympathetic overactivity (antihypertensives).
  • Medications:
    • Benzodiazepines: 1st-line option to decrease agitation, also lower BP
    • Antipsychotics might be helpful, especially in aggressive patients.
    • For ecstasy intoxication: Consider dantrolene (postsynaptic muscle relaxant).

Amphetamine withdrawal

Mainstay of treatment is supportive.


  • If suicidal, consider antidepressants.
  • Short course of benzodiazepines or antipsychotics might help to decrease irritability and anxiety.

Amphetamine use disorder

  • Physicians should try to build a rapport with patients to treat underlying mood disorders or personality disorders.
  • Psychotherapy and psychological interventions: 
    • Contingency management
    • Relapse prevention
    • Narcotics Anonymous
  • There is no FDA-approved pharmacotherapy for amphetamine dependence. 
  • Bupropion has proven to be helpful in supportive management.


Cardiovascular complications:

  • Leading cause of death among methamphetamine users
  • Arrhythmia 
  • Myocardial infarction 
  • Malignant hypertension 

Neurologic complications:

  • Hemorrhagic stroke: 5-fold increased risk 
  • Involuntary twitches, seizures
  • Coma 

Sexually transmitted diseases (STDs):

  • Methamphetamines increase libido and risky sexual behavior. 
  • IV injection increases the transmission of STDs.

Differential Diagnosis

  • Cocaine intoxication: Cocaine is an indirect sympathomimetic that blocks the reuptake of dopamine, epinephrine, and norepinephrine from the synaptic cleft, causing a stimulant effect (euphoria, increased energy, irritability, psychosis, decreased appetite, weight loss) similar to that of amphetamines. Withdrawal symptoms include severe depression and fatigue. Treatment options are limited and include benzodiazepines for acute intoxication as well as psychotherapy for long-term treatment. Amphetamines and cocaine are often taken together. 
  • Hallucinogen intoxication: Hallucinogens are substances that cause perceptual distortions (visual or auditory) that are used for their psychedelic effects (temporary altered state of consciousness). Similar to amphetamine intoxication, hallucinogen intoxication may lead to nausea, vomiting, and mild sympathomimetic effects (tachycardia, hypertension, mydriasis, hyperthermia, and diaphoresis). Hallucinogens do not result in physical dependence or withdrawal symptoms.
  • Inhalant intoxication: Inhalant use disorder involves the abuse of inhalant substances (e.g., glue, paint, lighter fluid). In order to reach euphoric effects, patients administer inhalers through the mouth (commonly known as huffing) or through the nose. The effect lasts for only several minutes. Signs of acute intoxication include transient euphoria and loss of consciousness. Intoxication can lead to CNS inhibition and cardiac arrhythmia. Treatment is supportive, but sedative drugs should be avoided, as they worsen intoxication.


  1. First Aid for the Psychiatry Clerkship, 4th ed. Chapter 7, Substance-related and addictive disorders, pages 80, 87–88.
  2. Kampman K. (2021). Pharmacotherapy for stimulant use disorders in adults. UpToDate. Retrieved February 21, 2021, from
  3. Substance Abuse and Mental Health Services Administration (2018). Key substance use and mental health indicators in the United States: Results from the 2017 National Survey on Drug Use and Health (HHS Publication No. SMA 18–5068, NSDUH Series H-53). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration.
  4. Sadock BJ, Sadock VA, Ruiz P. (2014). Substance use and addictive disorders. In: Kaplan and Sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry, 11th ed., pages 671–680. Philadelphia: Lippincott Williams and Wilkins.

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