Stimulant intoxication and withdrawal

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 product use and smoking cessation” 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.

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]

• Uncontrolled agents: caffeine, nicotine
• Prescription medications
  • Methylphenidate
  • Dextroamphetamine
  • Lisdexamfetamine
• Controlled substances
  • Cocaine
  • Amphetamine
  • Methamphetamine
  • MDMA
  • Cathinones
  • Ephedra

Mechanism of action ^[4]

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

• Increased release and/or inhibited reuptake of adrenaline, norepinephrine, serotonin, and dopamine → sympathetic stimulation, hallucinogenic effects
• Peripheral effects: ↑ heart rate, ↑ blood pressure, vasoconstriction
• Central effects: ↑ temperature, mydriasis, seizures, neuropsychiatric changes (e.g., agitation, anxiety, hallucinations)

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.

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

• Positive neuropsychiatric effects ^[3]
  • Increased concentration
  • Increased alertness and arousal
  • Euphoria and heightened feelings of well-being
  • Appetite suppression
  • Increased libido
• Negative neuropsychiatric effects
  • Disorganized thinking
  • Impaired judgment
  • Sleep disorders, prolonged wakefulness, hypervigilance
  • Megalomania
  • Psychotic symptoms, e.g., tactile hallucinations (formication) ^[6][7][8]

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

Physiologic effects

• Sympathomimetic toxidrome ^[10]
  • Hypertension
  • Tachycardia and/or tachyarrhythmias
  • Hyperthermia
  • Tachypnea
  • Diaphoresis
  • Mydriasis
  • Psychomotor agitation: anxiety, agitation, psychotic symptoms, e.g., delusions, hallucinations
  • Seizures and/or dyskinesias
• Other: hyperactive bowel sounds, nausea, chest pain, abdominal pain

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:
   • Evidence of weight loss
   • Mydriasis
   • Psychomotor agitation or retardation
   • Diaphoresis
   • Hypertension or hypotension
   • Tachycardia or bradycardia
   • Nausea and/or vomiting
   • Muscle weakness, chest pain, or arrhythmia
   • Neurological features: seizures, dyskinesias, coma

Differential diagnosis ^[10]

• Infection: sepsis, meningitis, encephalitis
• Alcohol withdrawal and/or sedative medication withdrawal
• Other causes of drug-induced hyperthermia
• Posterior reversible encephalopathy syndrome
• Pheochromocytoma
• Thyroid storm
• Status epilepticus
• Heatstroke

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]

• BMP
  • Hypoglycemia: due to hyperadrenergic state
  • Hyponatremia: especially with MDMA
  • Hyperkalemia: due to rhabdomyolysis
  • ↑ BUN and creatinine: may indicate renal failure
• ECG: may show tachyarrhythmia and/or features of myocardial ischemia ^[4]
• Urinalysis, CPK: ↑ CPK, hematuria, or myoglobinuria suggests rhabdomyolysis.
• Urine drug screening: rarely helpful for acute management
  • Cocaine: A positive test confirms the diagnosis.
  • Amphetamines: False positives may result from the use of other substances. ^[12]

Additional diagnostics ^[4][5]

Further diagnostic testing is guided by the clinical presentation.

• Chest pain: troponin to assess for myocardial ischemia
• Dyspnea: CXR and/or CT chest to assess for barotrauma, aspiration, and alveolitis
• Persistent hyperthermia: See “Diagnostic evaluation of fever.”
• Persistent CNS changes: CT head, additional diagnostics for altered mental status
• Abdominal pain: CT abdomen to assess for intestinal ischemia
• Evidence of bleeding or thrombosis: coagulation panel, CBC

Initial resuscitation ^[1][4][5]

• Conduct a primary survey in poisoning (including core temperature).
• Check blood glucose and begin IV fluid resuscitation.
• Administer benzodiazepines for stimulant intoxication as needed.
• Manage agitation and rapidly lower body temperature to ≤ 38.8°C (102°F).
• Manage hypertensive emergencies and cardiac arrhythmias.
• Replete electrolytes and treat hypoglycemia.
• Consider GI decontamination if stimulant intake was oral or body packing is suspected.
• Obtain additional diagnostics for stimulant intoxication as needed.

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]

• Indications
  • Agitation
  • Seizures
  • Hyperadrenergic state (e.g., hypertension, cardiac arrhythmia)
• Administration and monitoring
  • See “Benzodiazepines for agitation” for initial dosages.
  • Administer repeat doses until a clinical effect is seen. ^[4]
  • Benzodiazepines with rapid onset (e.g., midazolam or diazepam) are preferred because of a lower risk of oversedation. ^[4]
  • Consider IM administration if IV access cannot be obtained.
  • Monitor patients closely for signs of oversedation and paradoxical reactions to benzodiazepines.
• Adverse effects
  • Respiratory depression
  • Oversedation

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.

• Pharmacotherapy
  • Benzodiazepines for stimulant intoxication are preferred.
  • Consider; antipsychotics (e.g., haloperidol) as a first-line or in combination with benzodiazepines if psychotic features are present. ^[14][15]
  • Consider ketamine for refractory agitation. ^[13][16]
  • Other sedatives for refractory agitation include dexmedetomidine and propofol. ^[13]
• Additional considerations
  • Avoid restraints because they increase the risk of hyperthermia and rhabdomyolysis. ^[4]
  • Consider other critical causes of agitation (e.g., hypoxia, pain).
  • See also “Approach to agitated or violent patients” and “Treatment of acute psychosis.”

Hyperthermia ^[5]

• Rapidly cool patients to ≤ 38.8°C (102°F), ideally within 20 minutes.
• Initiate active cooling (see “Management of hyperthermia” for details).
• 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

• Reduce sympathetic tone with benzodiazepines for stimulant intoxication.
• If hypertension persists, consider phentolamine (off-label). ^[17]
• Alternative treatments include short-acting calcium channel blockers (e.g., clevidipine or nicardipine), hydralazine, and nitroglycerin.
• Beta blockers are generally avoided for treating stimulant-induced hypertension alone (see “Safety of beta blockers with stimulant use”).
• See “Management of hypertensive emergencies” for additional considerations and dosages.

Cardiac arrhythmias ^[4][18]

• Sedation, cooling, fluid resuscitation, and electrolyte repletion often suffice to resolve cardiac arrhythmias.
• For persistent supraventricular tachycardia (SVT), consider a calcium channel blocker.
• For persistent ventricular tachycardia (VT), administer hypertonic sodium bicarbonate. ^[19][20][21]
• Use beta blockers and class IA and class IC antiarrhythmics with caution (see “Safety of beta blockers with stimulant use”). ^[13][22]
• See also “Acute management of SVT” and “Initial management of VT.”

Chest pain ^[20]

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

• Differential diagnosis of chest pain in patients using stimulants ^[5]
  • Acute coronary syndrome (ACS), e.g., coronary vasospasm or thrombosis
  • Aortic dissection
  • Pulmonary barotrauma
  • Pulmonary infarction
  • Intestinal ischemia
• ACS suspected (e.g., cocaine-induced acute coronary syndrome): Follow the ACS management algorithm.
  • Reduce sympathetic tone with benzodiazepines for stimulant intoxication.
  • Give aspirin.
  • Manage hypertension with nitrates and/or phentolamine.
  • Consult a specialist about beta blockers (see “Safety of beta blockers with stimulant use”).

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

• Beta blockade in stimulant-induced cardiovascular toxicity is controversial, especially with nonselective beta blockers, due to concerns about unopposed alpha-adrenergic stimulation, which could worsen hypertension and coronary vasospasm.
• Beta blockers have been safely used in patients with stimulant use and concomitant ACS, hypertensive crises, acute heart failure, and tachyarrhythmias. ^[13][22][23]
• Many experts nevertheless recommend avoiding beta blockers in acute stimulant intoxication, especially if adequate alternatives are available. ^[24]
• Consider balancing this risk against the benefits of beta blockers for the individual patient, using shared decision-making. ^[23]
• Dual beta- and alpha-blockers (e.g., labetalol, carvedilol) are most likely safe. ^[13][22][23]

Other ^[4]

• Seizures
  • First-line: benzodiazepines
  • Second-line: barbiturates
  • See “Management of acute seizures” for additional recommendations.
• Vasospasm and/or thrombosis
  • Assess for signs of ACS, ischemic stroke, intestinal ischemia, and limb ischemia.
  • Obtain imaging to distinguish between vasospasm and thrombosis.
  • Vasospasm: Begin vasodilators (e.g., phentolamine, nitroglycerin, or nicardipine).
  • Thrombosis: Begin appropriate management depending on location, e.g., thrombolysis for ischemic stroke.
  • Percutaneous intervention or surgical revascularization may be required, e.g., for limb ischemia.
• Rhabdomyolysis: Manage rhabdomyolysis with aggressive IV fluid therapy.
• Flash pulmonary edema: See “Management of acute heart failure.”

Body packing ^[5][25][26]

• Obtain imaging, e.g., abdominal x-ray or CT abdomen
• Admit for whole-bowel irrigation and monitoring until all packets have passed.
• Ruptured packet
  • Urgent surgical consultation for operative GI decontamination
  • Interim stabilization with benzodiazepines for stimulant intoxication and other symptom-based therapies
• See “Body packing” for further details.

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

Disposition ^[4][5]

• Resolved symptoms and no sign of end-organ damage: Consider discharge after 4–6 hours of observation.
• Hyperthermia, rhabdomyolysis, and/or other evidence of end-organ damage: inpatient admission
• Patients with chest pain ^[20]
  • Perform risk stratification for acute coronary syndrome.
  • High risk: Admit to a monitored bed.
  • Low and intermediate-risk, resolved pain, and no ECG or troponin changes: Consider discharge after 9–12 hours of observation.
• Body packers: Admit until all packets have passed from the GI tract.
• All patients: Offer counseling on substance use disorders before discharge.

• Conduct a primary survey in poisoning and initiate resuscitation.
• Check core body temperature.
• Check blood glucose and treat hypoglycemia.
• Obtain BMP, CPK, ECG, UA, and urine drug screening.
• Begin IV fluid resuscitation.
• Begin sedation with benzodiazepines for stimulant intoxication.
• Lower body temperature to ≤ 38.8° C.
• Treat persistent hypertension with vasodilators, e.g., phentolamine.
• Treat supraventricular arrhythmias with calcium channel blockers
• Treat wide-complex arrhythmias with hypertonic sodium bicarbonate.
• Remain vigilant for rhabdomyolysis and end-organ damage caused by vasospasm.
• Consider discharge after observation for patients with resolved symptoms and no sign of end-organ damage.
• Admit patient if there are any signs of end-organ damage.

Acute ^[1][4][27]

• Cardiovascular
  • Vasospasm and ischemia: myocardial infarction, intestinal ischemia, ischemic stroke ^[28]
  • Cardiac tachyarrhythmias and sudden cardiac death
• Pulmonary (primarily with inhalation) ^[29]
  • Diffuse alveolar damage and hemorrhagic alveolitis (primarily with crack cocaine)
  • Barotrauma
  • Exacerbation of asthma
  • Pulmonary edema
• Other
  • Negative neuropsychiatric effects, e.g., psychosis
  • Serotonin syndrome (primarily after MDMA use)
  • Rhabdomyolysis-induced acute renal tubular necrosis (due to myoglobinuria)

Chronic ^[1][4][27]

• Cardiovascular
  • Myocarditis and/or cardiomyopathy
  • Accelerated atherosclerosis and necrotizing vasculitis
• Neuropsychiatric
  • Stimulant use disorder
  • Psychosis, depression, anxiety, suicide, violence ^[30][31]
  • CNS toxicity, e.g., Parkinson disease
  • Movement disorders ^[30]

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)
  • Severe dysphoria, depression, suicidal ideation
  • Anxiety and/or irritability
  • Fatigue, lethargy, and hypersomnia
  • Difficulty concentrating
  • Hunger, headaches, body aches, dental pain
  • Unpleasant, vivid dreams
• 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:
   • Fatigue
   • Psychomotor slowing or agitation
   • Somnolence, lethargy, or insomnia
   • Increased appetite
   • Sleep disturbance, vivid nightmares
2. Clinically significant distress or functional impairment resulting from the above features

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

General principles

• Management is primarily supportive, with an emphasis on preventing self-harm. ^[32]
• Provide symptomatic treatment as needed (e.g., management of acute panic attacks, management of agitation).
• Screen for substance use disorders involving other substances, as patients may self-medicate and/or experience withdrawal.
• Remain vigilant for evidence of concurrent psychiatric disorders and suicidal ideation.

Consults and disposition

• Consult psychiatry for evaluation and treatment of depression, suicidal ideation, and/or substance use disorders.
• Acute symptoms are typically safe to manage in an outpatient withdrawal management setting.
• Consider admission for inpatient withdrawal management if the patient has:
  • Severe psychiatric symptoms
  • Severe polysubstance use
  • Unsafe living conditions, e.g., is experiencing intimate partner violence

Background ^[1][4]

• Routes of administration ^[27][34]
  • Crystallized freebase (crack): smoked, injected
  • Water-soluble salts (“coke,” “blow,” “snow”): nasal inhalation, intravenous
• Mechanism of action
  • Inhibition of dopamine, serotonin, epinephrine, and norepinephrine reuptake → increased synaptic neurotransmitter concentration → autonomic stimulation, CNS excitation
  • Inhibition of Na⁺ channels → slowed neuronal action potential transmission → local anesthesia, arrhythmias
• Half-life: 40–90 minutes ^[1]
• Therapeutic uses (limited)
  • Diagnosis of Horner syndrome: Topical cocaine causes mydriasis in an eye with intact sympathetic innervation, but not in an eye with sympathetic denervation. ^[35]
  • Topical anesthesia for otolaryngology procedures

Cocaine intoxication ^[4][5]

• Clinical features
  • Clinical features of stimulant intoxication, e.g., sympathomimetic toxidrome, euphoria
  • Chest pain and/or angina due to cocaine-induced coronary vasospasm
• Treatment: : See “Management of stimulant intoxication.”

Cocaine withdrawal ^[4][5]

• Clinical features
  • Clinical features of stimulant withdrawal, e.g., fatigue, anhedonia
  • Physiologic crash: severe depression with suicidal ideation, constricted pupils, psychomotor agitation
• Management: : See “Management of stimulant withdrawal.”

Complications of cocaine use

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

• Cocaine-induced vasospasm
  • ↓ Reuptake of norepinephrine → ↑ α- and β₁‑stimulation → vasoconstriction and vasospasm
  • Manifestations include myocardial infarction, cerebrovascular accident, and ischemic colitis
• Rhabdomyolysis ^[36]
  • Multifactorial: direct myocyte toxicity, ischemia caused by vasospasm, and/or compartment syndrome ^[4]
  • Myoglobinuria can lead to acute renal tubular necrosis.
• Acute pulmonary cocaine toxicity (crack lung) ^[29]
  • Pulmonary syndrome of diffuse alveolar damage and hemorrhagic alveolitis that occurs within 48 hours of crack cocaine inhalation
  • Histopathology: alveolar hemorrhage, alveolar and interstitial eosinophil infiltration, diffuse alveolar damage
  • Clinical findings: dyspnea, chest pain, productive cough, fever, hemoptysis, hypoxemic respiratory failure
  • Radiographic findings: atelectasis, pulmonary edema, pneumothorax, pneumomediastinum, diffuse ground glass opacities, consolidation
• Nasal pathology
  • Nasal inhalation can damage nasal blood vessels and result in epistaxis.
  • Chronic local vasoconstriction may cause ischemic necrosis and perforation of the nasal septum.
• Substance use disorders: cocaine use disorder

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

Background ^[4]

• Definition: a group of compounds with a shared phenylethylamine structure
• Substances
  • Alpha-methylphenethylamine (“speed”)
  • Methamphetamine (“meth,” “crank”)
  • 3,4-Methylenedioxymethamphetamine (“MDMA,” “ecstasy,” “molly”)
  • Cathinone (“bath salts”)
• Mechanism of action: ↑ release and ↓ reuptake of presynaptic monoamine neurotransmitters (e.g., adrenaline, norepinephrine, serotonin, and dopamine)
  • Central effect: CNS sympathetic stimulation and hallucinogenic effects
  • Peripheral effect: tachycardia, hypertension, arrhythmias

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

Amphetamine intoxication

• Clinical features
  • Clinical features of stimulant intoxication, e.g., sympathomimetic toxidrome ^[10]
  • Behavioral changes: disorganized thinking, impaired judgment, increased libido, bruxism, sleep disorders ^[37]
  • Physical exam findings: skin excoriations due to formication
  • See individual drugs for unique concerns.
• Management: : See “Management of stimulant intoxication.”

Amphetamine withdrawal

• Clinical features
  • Clinical features of stimulant withdrawal
  • Physiologic crash after use due to receptor downregulation
• Management: See “Management of stimulant withdrawal.”

Complications of amphetamine use

• General complications of stimulant intoxication, e.g., rhabdomyolysis
• Memory impairment (especially with chronic MDMA use) ^[38]
• Ongoing anxiety, mood disorders, or psychosis
• Amphetamine use disorder

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]

• Clinical features
  • Typical clinical features of stimulant intoxication, e.g., agitation
  • High incidence of psychological and behavioral symptoms and psychosis ^[41]
• Management: See “Management of stimulant intoxication.”

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]

• Clinical features
  • Psychological symptoms of stimulant withdrawal (e.g., depression) may be severe.
  • Drug craving can be more pronounced than with other stimulants (e.g., MDMA). ^[43]
• Management: See “Management of stimulant withdrawal.”

Complications of chronic use ^[40]

• Chronic psychological and behavioral changes, including high-risk sexual behavior
• CNS toxicity: e.g., substance-induced psychosis, cognitive impairment, CNS vasculitis ^[44]
• Dental disorders (e.g., tooth decay, dental injuries): typically related to xerostomia and/or bruxism

Background ^[4][45]

• Substance: 3,4-methylenedioxymethamphetamine (MDMA)
• Street names: ecstasy, E, molly
• Route of administration: oral
• Mechanism of action
  • ↑ Release and ↓ reuptake of serotonin, dopamine, and norepinephrine
  • MDMA increases secretion of antidiuretic hormone (ADH) → thirst → increased water intake without electrolyte repletion → hyponatremia
• Half-life: ∼ 9 hours ^[46]

MDMA intoxication ^[45][46]

• Clinical features
  • Clinical features of stimulant intoxication, e.g., sympathetic toxidrome, euphoria, agitation
  • Entactogen: social empathy (feeling of “oneness”), loss of anxiety, promotion of introspection and personal reflection ^[47]
  • Hyponatremia: can manifest with seizures, cerebral and/or pulmonary edema
  • Features of serotonin syndrome (especially with concomitant use of an SSRI)
  • Other: grinding teeth (bruxism), trismus, distorted perceptions of sensation and time
• Management ^[5]
  • See “Management of stimulant intoxication.”
  • Treat hyponatremia with fluid restriction and hypertonic saline.
  • Manage serotonin syndrome.

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]

• Clinical features
  • Physical symptoms of withdrawal are uncommon.
  • Psychological symptoms of withdrawal are similar to other stimulants: See “Clinical features of stimulant withdrawal.”
• Management: See “Management of stimulant withdrawal.”

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 (can last for several days) ^[52]

Cathinone intoxication ^[51]

• Clinical features
  • Typical clinical features of stimulant intoxication (e.g., hyperthermia, mydriasis)
  • Negative neuropsychiatric effects include agitation, hallucinations, paranoia, and aggression.
  • Hyponatremia occurs with some synthetic cathinones.
• Diagnostics: Synthetic cathinones cannot be detected with routine urine toxicology screening.
• Management
  • Provide supportive care.
  • See “Management of stimulant intoxication.”

Cathinone withdrawal ^[51]

• Clinical features: Symptoms of stimulant withdrawal may begin immediately after stopping use.
• Management: See “Management of stimulant withdrawal.”

Complications ^[51][53]

See also “Complications of stimulant use.”

• Acute
  • Acute renal failure
  • Myocardial infarction
  • Rhabdomyolysis
• Chronic
  • Insomnia
  • Impaired memory
  • Psychosis
  • Parkinson disease ^[4]

Background ^[4]

• Stimulants are prescribed to improve alertness, attention, and energy for a variety of indications, e.g.:
  • FDA approved: ADHD, narcolepsy
  • Off-label: refractory depression, cancer fatigue ^[54]
• 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. ^[55]
• See “Treatment of ADHD” for further details.

Examples ^[4]

• Amphetamines, e.g., Adderall
• Methamphetamine, e.g., Desoxyn
• Lisdexamfetamine, e.g., Vyvanse ^[56]
• Dextroamphetamine, e.g., Dexedrine
• Methylphenidate, e.g., Ritalin ^[57]

Management ^[4]

• Prescription stimulant intoxication is a clinical diagnosis.
• Urine drug screening (e.g., for amphetamines) cannot help distinguish prescribed use from overdose.
• Provide general management of stimulant intoxication for symptomatic patients.
• Initiate management of substance use disorders, if present.

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