Stimulant intoxication and withdrawal

Last updated: September 26, 2023

Summarytoggle arrow icon

Stimulants encompass a wide variety of prescription and recreational drugs that are used to enhance arousal and/or alter mood and awareness. Nicotine and caffeine are the most commonly used uncontrolled stimulants. Amphetamines and cocaine are among the most commonly encountered controlled stimulants. Stimulants can also be prescribed medications, e.g., for attention deficit hyperactivity disorder. All stimulants have the potential for dependence and substance misuse. Most stimulants achieve their desired neuropsychiatric effect by increasing the concentration of synaptic neurotransmitters in the central nervous system, but a simultaneous increase of neurotransmitters in the peripheral nervous system can cause generalized sympathetic nervous system hyperactivity. Stimulant intoxication often manifests in a sympathomimetic toxidrome (agitation, hyperthermia, tachycardia, and hypertension) and may result in rapid end-organ damage and/or sudden death. Treatment focuses on rapidly controlling agitation, hyperthermia, and hypertension. Chronic stimulant use may cause complications related to long-standing sympathetic stimulation (e.g., cardiomyopathy) or direct tissue toxicity (e.g., CNS damage). Withdrawal from chronic stimulant use is not typically associated with severe physiologic effects but may have profound psychological effects, e.g., suicidal ideation.

For the mechanisms of action and specific considerations for nicotine and caffeine, see “Tobacco-related disorders” and “Caffeine-related disorders.”

See also “Sympathomimetic drugs” for details on stimulant pharmacology and “Substance-related and addictive disorders” for details on managing related substance-use disorders.

Overviewtoggle arrow icon

Simulants are used clinically and recreationally for their positive neuropsychiatric effects (see “Clinical features of stimulant intoxication”).

Definitions [1][2][3]

The terms psychostimulant and stimulant are often used interchangeably in clinical practice, although their meanings are different.

  • Stimulant: a nonspecific term for agents that increase the functional activity or efficiency of an individual and/or organ
  • Psychostimulant: a psychotropic agent that stimulates the CNS, usually causing excitation, mood elevation, and/or increased arousal

Substances [2][4]

Mechanism of action [4]

Most stimulants work by increasing the synaptic concentration of neurotransmitters. See “Nicotine” and “Caffeine” for their unique effects.

Benzodiazepines are the first-line treatment for stimulant intoxication because they control agitation and reduce the excessive sympathetic tone that contributes to potentially lethal hyperthermia, hypertension, and cardiac arrhythmias.

Stimulant intoxicationtoggle arrow icon

Clinical features of stimulant intoxication [1][4][5]

  • The neuropsychiatric and physiologic effects of stimulant use are highly variable and dose-dependent.
  • The distinction between desired effect and overdose is also variable and depends on the patient, stimulant, and the context of exposure (especially with recreational use).

Neuropsychiatric effects

Stimulants can trigger substance-induced psychosis, especially in individuals with high-dose, daily use, and/or other risk factors for psychosis. [9]

Physiologic effects

DSM-V criteria for stimulant intoxication [11]

Both criteria must be fulfilled during or shortly after the use of a stimulant and not be attributable to another cause.

  1. Behavioral/mental features: euphoria, mood elevation, anxiety, anger, impaired judgment, etc.
  2. At least 2 of the following somatic features:

Differential diagnosis [10]

Diagnosistoggle arrow icon

Initial management of stimulant intoxication is based on the clinical diagnosis. Diagnostic testing is primarily used to identify alternative diagnoses and/or complications.

Initial diagnostics [4][5]

Additional diagnostics [4][5]

Further diagnostic testing is guided by the clinical presentation.

Managementtoggle arrow icon

Initial resuscitation [1][4][5]

During initial management, focus on controlling agitation and hyperadrenergic state with benzodiazepines and lowering the body temperature to ≤ 38.8° C with ice baths. [5]

Avoid succinylcholine for airway management and muscle relaxation because it may precipitate fatal hyperkalemia in patients with rhabdomyolysis. [4][5]

Benzodiazepines for stimulant intoxication [4][5][13]

Benzodiazepines are administered until a clinical effect is seen. Large doses are often required, e.g. 1 mg/kg of diazepam. [4]

Symptom-based management

Agitation [5][13]

Immediate sedation is the primary treatment for agitation caused by stimulant intoxication.

Hyperthermia [5]

  • Rapidly cool patients to ≤ 38.8°C (102°F), ideally within 20 minutes.
  • Methods include immersion in ice water baths and cooling devices.
  • Sedation reduces heat generation, but additional muscle relaxation may be required for adequate cooling. [4]
  • Institute continuous monitoring of core temperature.

Cardiovascular symptoms

Hypertensive emergencies

Cardiac arrhythmias [4][18]

Chest pain [20]

Chest pain is a common symptom in patients who have used stimulants (especially cocaine).

Safety of beta blockers with stimulant use [13][22][23]

Other [4]

Body packing [5][25][26]

Do not delay operative therapy in patients with ruptured packets filled with stimulants. [5][25][26]

Disposition [4][5]

Acute management checklisttoggle arrow icon

Complicationstoggle arrow icon

Acute [1][4][27]

Chronic [1][4][27]

Stimulant withdrawaltoggle arrow icon

Clinical features of stimulant withdrawal [1][32][33]

Symptoms of withdrawal occur in most individuals who abruptly discontinue stimulants after prolonged use, typically within 24 hours of stimulant cessation.

  • Acute phase (first week, peak at 2–3 days)
  • Protracted phase (weeks to months)
    • Cognitive dysfunction (e.g., impaired memory)
    • Difficulty making decisions
    • Anhedonia, anxiety, and/or depression
    • Cravings, drug-related dreams

While the physiologic signs and symptoms are not typically life-threatening, the psychological symptoms of withdrawal are severe. They may lead individuals to start using stimulants again and carry a high risk of self-harm. [1]

DSM-V criteria for stimulant withdrawal [11]

Both criteria must be fulfilled and not be attributable to another cause.

  1. Dysphoria and at least 2 of the following symptoms occurring within hours to days of stimulant cessation:
  2. Clinically significant distress or functional impairment resulting from the above features

Management of stimulant withdrawal [1][32][33]

General principles

Consults and disposition

Cocainetoggle arrow icon

Background [1][4]

Cocaine intoxication [4][5]

Cocaine withdrawal [4][5]

Complications of cocaine use

The following are common complications of stimulant use associated with cocaine:

Suspect cocaine use in individuals with weight loss, behavioral changes, and erythema of the turbinates and nasal septum.

Amphetaminestoggle arrow icon

Background [4]

Amphetamines are controlled substances in the United States, along with some precursors to amphetamine synthesis, e.g., pseudoephedrine and ephedrine.

Amphetamine intoxication

Amphetamine withdrawal

Complications of amphetamine use

Methamphetaminestoggle arrow icon

Background [4][39]

  • Street names: meth, crank, ice, crystal meth
  • Route of administration: smoked (most common), injected, inhaled, oral, sublingual
  • Mechanism of action: similar to amphetamines but with higher potency and a longer duration of action [38]

Methamphetamine intoxication [39][40]

Fatalities from acute methamphetamine intoxication are typically related to vascular complications. Remain vigilant for acute coronary syndrome, acute stroke, and tachyarrhythmias in these patients. [42]

Methamphetamine withdrawal [1][39]

Complications of chronic use [40]

MDMAtoggle arrow icon

Background [4][45]

MDMA intoxication [45][46]

Common preventive actions to avoid harm from MDMA include prehydration with water or isotonic solutions, limiting or reducing drug use, taking breaks, and testing ingested drugs for other substances. [48][49]

MDMA withdrawal [45]

Cathinonestoggle arrow icon

Background [50][51]

Cathinones are chemically similar to amphetamines and have similar clinical effects.

  • Substances
    • Naturally occurring cathinone is found in Catha edulis plant and is released by chewing on the leaves.
    • Synthetic cathinones
    • Bupropion is the only cathinone with a medical indication. [4]
  • Street names
    • Naturally occurring: khat, qat, kat, chat, miraa
    • Synthetic: bath salts, bloom, vanilla sky
  • Mechanism of action: ↑ release and ↓ reuptake of monoamines (norepinephrine, dopamine, serotonin) → sympathetic stimulation and hallucinogenic effects

Cathinone intoxication [51]

Cathinone withdrawal [51]

Complications [51][52]

See also “Complications of stimulant use.”

Prescription stimulantstoggle arrow icon

Background [4]

  • Stimulants are prescribed to improve alertness, attention, and energy for a variety of indications, e.g.:
  • Half-life is highly variable, as both immediate-release and long-acting formulations are available.
  • Patients can develop related substance use disorders, as tolerance reduces medication efficacy over time and stimulant withdrawal can occur.
  • Adverse effects at therapeutic doses include insomnia, weight loss, nausea, and headaches.
  • Substance misuse of stimulants often occurs in high-performance and academic environments, e.g., among college students. [54]
  • See “Treatment of ADHD” for further details.

Examples [4]

Management [4]

Referencestoggle arrow icon

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