Acute intoxication — Typical cocaine doses are 12 to 15 g orally (coca leaf), 20 to 100 mg intranasally, 10 to 50 mg intravenously, and 50 to 200 mg smoked. The intended effects include increased energy, alertness, and sociability; elation or euphoria; and decreased fatigue, need for sleep, and appetite. The intense pleasurable feeling has been described as a “total body orgasm”.

There is wide variability in the acute response to cocaine and poor correlation between cocaine plasma concentrations and toxic effects . Fatal cases of cocaine intoxication may present with 100-fold differences in plasma cocaine concentration.

Unintended adverse effects occur with increasing dose, duration of use, or a more efficient route of administration (eg, intravenous or smoked versus intranasal). These effects include dysphoric mood (anxiety, irritability), panic attacks, suspiciousness, paranoia, grandiosity, impaired judgment, and psychotic symptoms such as delusions and hallucinations. Up to 40 percent of non-treatment-seeking cocaine users may experience sleep disturbance, weight loss (due to appetite suppression), paranoia, or hallucinations. Concurrent behavioral effects include restlessness, agitation, tremor, dyskinesia, and repetitive or stereotyped behaviors such as picking at the skin or foraging for drugs (“punding,” “hung-up activity”). Associated physiological effects include tachycardia, pupil dilation, diaphoresis, and nausea, reflecting stimulation of the sympathetic nervous system.

A detailed discussion of the presentation and treatment of cocaine intoxication is presented separately.

Chronic use — Chronic cocaine use can result in either of two distinct pharmacological adaptations: sensitization (increased drug response) and tolerance (decreased drug response). In animal studies, sensitization results from low-dose, intermittent exposure, while tolerance results from frequent, high-dose, or long-term exposure.

The factors that determine sensitization and tolerance in humans, however, are not well understood. Sensitization to the cardiovascular effects of oral cocaine, but not to its psychological effects, has been demonstrated in laboratory studies. Tolerance to the psychological, cardiovascular, and neuroendocrine effects of cocaine develops after several doses. Tolerance to cardiovascular effects may develop more quickly and completely than does tolerance to psychological effects. This rapid tolerance presumably allows binge users to take large cumulative doses of cocaine.

Chronic cocaine abuse is associated with cognitive impairment affecting visuo-motor performance, attention, verbal memory, and risk-reward decision-making. These impairments persist for at least several weeks of abstinence.

Cocaine use is associated with suicidal ideation and suicide attempts. The extent to which suicide is a direct consequence of use, rather than an associated sociodemographic or psychological factor, remains unclear. Factors associated with increased risk of suicidality among cocaine users include depression, severe cocaine withdrawal, comorbid alcohol or opioid dependence, history of childhood trauma, and family history of suicidality.

Chronic cocaine use by any route of administration is associated with increased risk of infection, especially viral hepatitis and HIV.

Chronic cocaine use does not appear to increase the risk of general anesthesia, as long as the patient has normal cardiovascular parameters at the time of surgery.

Withdrawal symptoms — Cessation of heavy chronic cocaine use results in a withdrawal syndrome that has prominent psychological features but is rarely medically serious. Symptoms include depression, anxiety, fatigue, difficulty concentrating, decreased ability to experience pleasure (anhedonia), increased cocaine craving, increased appetite, increased sleep, and increased dreaming (due to increased REM sleep). An initial period of intense symptoms (commonly termed the “crash”) may occur, including psychomotor retardation and severe depression with suicidal ideation. However, most users experience milder symptoms that resolve within one to two weeks without treatment.

Physical signs of cocaine withdrawal are usually minor and rarely require treatment. These include nonspecific musculoskeletal pain, tremors, chills, and involuntary motor movement. The first week of stimulant withdrawal has been associated with myocardial ischemia, possibly due to coronary vasospasm.

Author
David A Gorelick, MD, PhD

Deputy Editor
H Nancy Sokol, MD

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