Etiology

Genomic studies and twin and family cohort studies suggest that there are genes with allelic variants that do predispose to stimulant dependence.[12][13]​ Dopamine-rich neurons in the shell of the nucleus accumbens are deeply involved in the process of addiction to all drugs, and numerous polymorphisms can alter dopamine metabolism, signaling, and signal regulation.[14]​ Genome-wide association studies have implicated the FAM53B (family with sequence similarity 53, member B) gene and the KCTD20 (potassium channel tetramerization domain) gene in cocaine use and dependence; however, these findings require replication in independent studies.[15][16]

Pathophysiology

Cocaine exerts multiple effects. Many of these are mediated by prevention of the reuptake of norepinephrine, producing a transient hyperadrenergic state. Cocaine prevents the re-uptake of all catecholamines.

Both cocaine and methamphetamine directly activate DNA to produce increased amounts of calmodulin-kinase II. This leads to myocardial hypertrophy and to increased calcium within the cytosol of cardiomyocytes.[17][18]​ Both actions favor the occurrence of arrhythmias.[19] Acute elevation of catecholamines can precipitate acute myocardial infarction in those with underlying coronary disease, and stroke in those with pre-existing cerebral malformations.

Acute toxicity is more or less dose related, but tolerance emerges with the first dose. Chronic use is associated with neurochemical and anatomic changes that can be associated with toxicity, or less commonly with death. It is generally accepted that there is no relationship between blood cocaine concentrations measured just before death and levels measured at autopsy, and in neither case is there a relationship between cocaine concentrations and symptoms observed.

Most cocaine sold today has been adulterated with levamisole. Levamisole can cause aplastic anemia, but mainly brings patients to the emergency room because of retiform vasculopathy that may be accompanied by neutropenia, agranulocytosis, thrombotic vasculopathy, and purpura confined to the face and ears.[20] Necrosis of the ear lobes has also been reported.

Classification

International classification of diseases 11th revision (ICD-11)[2]

Disorder due to use of cocaine

Primary diagnosis of a disorder due to use of cocaine should include a pattern of cocaine use along with the impact of the pattern of cocaine use.

Pattern of cocaine use:

  • Episode of harmful use of cocaine

  • Harmful pattern of use of cocaine

    • Harmful pattern of use of cocaine, episodic

    • Harmful pattern of use of cocaine, continuous

    • Harmful pattern of use of cocaine, unspecified

  • Cocaine dependence

    • Cocaine dependence, current use

    • Cocaine dependence, early full remission

    • Cocaine dependence, sustained partial remission

    • Cocaine dependence, sustained full remission

    • Cocaine dependence, unspecified

Impact of the pattern of cocaine use

  • Cocaine intoxication

  • Cocaine withdrawal

  • Cocaine-induced delirium

  • Cocaine-induced psychotic disorder

    • Cocaine-induced psychotic disorder with hallucinations

    • Cocaine-induced psychotic disorder with delusions

    • Cocaine-induced psychotic disorder with mixed psychotic symptoms

    • Cocaine-induced psychotic disorder, unspecified

  • Certain specified cocaine-induced mental or behavioral disorders

    • Cocaine-induced mood disorder

    • Cocaine-induced anxiety disorder

    • Cocaine-induced obsessive compulsive or related disorder

    • Cocaine-induced impulse control disorder

  • Other specified disorder due to use of cocaine

  • Disorder due to use of cocaine, unspecified

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