Cocaine Use Disorder

Cocaine use disorder is a substance use disorder defined by pathologic consumption of the recreational drug cocaine. Cocaine is an indirect sympathomimetic that blocks the reuptake of dopamine, serotonin, and norepinephrine from the synaptic cleft. This process causes stimulant effects on the body and mind such as euphoria, increased energy, irritability, psychosis, decreased appetite, and weight loss. Cocaine overdose can cause death secondary to cardiac arrhythmia, myocardial infarction, seizure, or respiratory depression. Prognosis is poor as there is no approved pharmacological treatment, but psychosocial interventions have been associated with improved outcome.

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Definition and Epidemiology


Cocaine use disorder is defined as the chronic (> 12 months) maladaptive use of the recreational drug cocaine. 

  • Intoxication: 
    • Heightened sense of arousal, alertness, as well as euphoria for a brief period of time
    • May cause end-organ toxicity in multiple organ systems 
  • Withdrawal: 
    • Development of a substance-specific syndrome due to the cessation (or reduction) of substance use
    • Leads to physical (nausea, diarrhea, chills, body aches) and/or psychological symptoms (cravings or perceived need to use the substance)
  • Tolerance: 
    • The need to increase the dose of the substance to achieve the desired effect (diminished effect if using the same amount of the substance)


  • Prevalence in the United States: 
    • Approximately 2.2 million regular users of cocaine 
    • Of those, 1 million individuals meet criteria for cocaine use disorder.  
  • Limited medical use (used to be administered as a local anaesthetic); most cocaine use is recreational
  • Frequently misused as a performance-enhancing drug
  • Cocaine is involved in an estimated 40% of recreational drug-related ED visits, higher than cannabis and any opioid.


Types of cocaine

  • Cocaine hydrochloride salt:  
    • Water-soluble formulation 
    • Can be ingested orally, intranasally, or intravenously
  • Freebase cocaine (“crack”):
    • Heat-stable formulation that can be smoked
    • Very rapid onset of action 
    • Extremely addictive


  • Cocaine is an indirect sympathomimetic → blocks the reuptake of dopamine, epinephrine, and norepinephrine from the synaptic cleft
  • Increased norepinephrine stimulates:
    • α1– and α2-adrenergic receptors 
    • β1– and β2-adrenergic receptors
  • Most important effects on the body: 
    • Transient sense of euphoria, mental alertness, decreased hunger 
    • Increase in norepinephrine →  potent vasoconstrictor → may lead to severe hypertension, myocardial infarction, stroke 
    • Direct cardiac toxicity of cocaine → tachycardia, hypertension, coronary spasms

Clinical Presentation

Cocaine intoxication

  • General: 
    • Weight loss
    • Chills and sweating
  • CNS: 
    • Euphoria
    • Increased self-esteem
    • Dilated pupils 
    • Stimulant-induced psychotic disorder
    • Loss of inhibitions
    • Increased libido
  • Cardiovascular: 
    • ↑ Or ↓ blood pressure
    • Tachycardia or bradycardia
  • GI: 
    • Nausea
    • Loss of appetite
    • Dry mouth

Cocaine withdrawal

  • Patient enters a state of severe depression after intoxication (known as “crash” phase). 
  • Generally not life-threatening; however, patient may develop suicidal ideation
  • General symptoms:
    • Malaise
    • Fatigue
    • Disturbed sleep
    • Anhedonia
    • Irritability with psychomotor agitation or retardation
  • CNS: constricted pupils
  • GI: hunger


Cocaine intoxication

The management of cocaine intoxication depends on the severity of symptoms.

  • Mild-to-moderate agitation and anxiety: 
    • Reassurance
    • Benzodiazepines for sedation
  • Severe agitation or psychosis: 
    • Antipsychotics (e.g., haloperidol) and benzodiazepines for sedation
    • Symptomatic support (i.e., control of hypertension and arrhythmias)
    • Treating hyperthermia (ice bath, cooling blanket)
  • Potentially fatal symptoms: 
    • Treat according to protocol for each condition (see “Complications”).
    • Avoid use of beta-blockers for treatment of cocaine-induced myocardial infarction!

Cocaine withdrawal

  • Mild-to-moderate use: Symptoms resolve within 72 hours.
  • Heavy, chronic use: Symptoms last for 1–2 weeks.
  • Treatment is supportive. 
  • Hospitalization:
    • Not generally indicated for detoxification from cocaine 
    • Indicated in patients with severe psychiatric symptoms

Cocaine use disorder

  • There is no Food and Drug Administration (FDA)-approved pharmacotherapy for cocaine dependence. 
  • However, some medications have proven to be helpful:
    • Bupropion
    • Cholinergic medications: galantamine
    • Gabanergic medications: vigabatrin and topiramate
  • 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 (NA)


Cardiovascular complications

  • Myocardial infarction: 
    • Due to severe coronary vasoconstriction → ischemic damage
    • Giving beta-blockers in this case is contraindicated!  
  • Arrhythmias
  • Aortic dissection
  • Heart failure
  • Pulmonary hypertension

Neurologic complications

  • Psychomotor agitation through release of excitatory amino acids and neurotransmitters in the CNS
  • Hyperthermia: Body is unable to dissipate the heat produced from constant agitation due to peripheral vasoconstriction. 
  • Seizures 
  • Ischemic and hemorrhagic strokes 
  • Respiratory depression

Nasal septal perforation

  • Vasoconstriction in nasal septum arteries
  • Nasal septal perforation in chronic use (due to ischemic necrosis and severe vasoconstriction)

Effects on pregnancy

  • Effect on mother: increases risk of abruptio placentae (placenta is either completely or partially detached prior to birth)
  • Fetal effects: 
    • Increased fetal morbidity and mortality
    • Fetal cortical cystic lesions
    • Intrauterine growth restriction → low birth weight 
    • Preterm birth

Differential Diagnosis

  • Amphetamine use disorder: Amphetamines are stimulant drugs, producing their effect by increasing the release and blocking the reuptake of neurotransmitters (dopamine, norepinephrine, serotonin). Amphetamines are used for treating ADHD, narcolepsy, and obesity, but are often abused for their stimulating effects. Intoxication results in effects similar to those of cocaine: euphoria, pupillary dilation, hypertension, skin excoriation, paranoia, and fever. Withdrawal symptoms include increased appetite, severe depression, fatigue, and vivid dreams. Amphetamines and cocaine are often consumed together. 
  • Hallucinogen intoxication: Hallucinogens are substances that cause perceptual distortions (visual or auditory). Examples include LSD (lysergic acid diethylamide), ketamine, and dextromethorphan. Hallucinogens are used for their psychedelic effects, which temporarily lead to an altered state of consciousness. Similar to cocaine intoxication, hallucinogen intoxications produce nausea, vomiting, and mild sympathomimetic effects (e.g., tachycardia, hypertension, mydriasis, hyperthermia, and diaphoresis). Hallucinogens do not result in dependence or withdrawal symptoms.
    Inhalant intoxication: the abuse of inhalant substances such as glue, paint, or lighter fluid. In order to reach euphoric effects, patients administer inhalers through the mouth (commonly known as “huffing”) or sniff substances through the nose. The effect lasts only for several minutes. Signs of acute intoxication include transient euphoria up to loss of consciousness. Inhalants result in CNS inhibition and cardiac arrhythmia. Treatment is supportive, and sedative drugs should be avoided as they tend to worsen intoxication.


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