Cocaine

Karen Drexler, M.D.

Epidemiology

1995 National Household Survey on Drug Abuse

1.5 million Americans or 0.7% of the population ages 12 and older are current cocaine users.

This is stable after a high of 3% of the population in 1985.

Ethnography

Among youth (12 - 17 years)

Use was higher in Blacks (1.1%), than in Hispanics (0.7%), than in Whites (0.6%)

Use was higher in men (1%) than women (0.4%)

Current cocaine use was inversely correlated with education

Use was higher among the unemployed (2%) than employed (0.7%)

Cocaine: Historical perspectives

1400s: Coca leaves have been chewed by native Andean peoples

Provides energy, decreases hunger, improves sense of well-being

Average daily dose: 200 - 300 mg per day

Cocaine: Historical perspectives

1850s: Explorers and botanists brought coca to Europe

Wine of Coca

Cocaine HCl powder praised as a stimulant for athletes, workers, and students.

Medicinal uses included anesthesia, Rx for sinusitis and hay fever

Average daily dose was 225 - 1620 mg per day.

Cocaine: Historical perspectives

1880s: Cocaine becomes widely available

S. Freud publishes "Uber Coca"

Praises cocaine as an antidepressant, aphrodisiac, anesthetic

John Pemberton develops Coca Cola

Markets it as a "temperance drink" and "brain tonic"
Coca Cola contains about 60 mg. cocaine per 8 oz. serving

Cocaine: Historical perspectives

1890s: First concern about the dangers of cocaine

Freud accused of "unleashing the third scourge of humanity."

1903: Coca Cola voluntarily removes cocaine from its product.

1914: The Harrison Narcotic Act

Bans cocaine in over-the-counter medications.

Cocaine: Historical perspectives

1930s: Amphetamines and other synthetic stimulants

Cheaper

Longer lasting high

1960s: "Speed Kills"

1970s: Cocaine marketed as a "safe" recreational stimulant

Cocaine: Historical perspectives

Mid-1980s: Availability of cocaine increases, price drops.

Amount of a typical dose increases

"Freebasing" allows users to ingest higher amounts than ever before.

"Speedball" combines cocaine and heroin.

Cocaine: Historical perspectives

Mid- 1980s: "Crack," mass-produced free-base cocaine

Low price (as little as $3 per dose)

Rapid onset (10 seconds)

Rapid elimination (wears off in 5 to 15 minutes)

More powerful euphoria

Typical 300 mg per rock.

Cocaine: Historical perspectives

Late 1980s: Negative reports escalate

1986: Anti-Drug Abuse Act- emphasizes interdiction

1988: War on Drugs dominates the national politics

Spurred on by the deaths of young athletes and entertainers
And by increase in crime and violence

Cocaine: Historical Perspectives

1990s:

Casual use drops

Dependence becomes endemic

Replaced by amphetamines in some regions

Cocaine: Pharmacology

Blocks reuptake of norepinephrine, serotonin, and dopamine.

Elimination half-life is 1 hour for free-base, crack or iv use

Cocaine hydrochloride

May be insufflated "tooted" or injected IV

Street purchase of 1 gm = 30 lines (averaging 10 to 35 mg)

Bioavailability of intranasal cocaine is about 60%, 100% from IV.

Peak plasma level in 30 to 120 minutes from insufflation, immediate from IV.

Coca paste

Intermediate product in the production of cocaine HCl

Popular in South America, but also U.S.

"Pasta" or "bazooka" is 45 - 80% cocaine sulfate

Gray-white or dull brown paste or powder which is smoked

Free-base cocaine

Obtained by extracting cocaine HCL with an alkali (ammonia)

Then mixing with a solvent such as ether

Freebase is lipid soluble and immediately crosses the lung-blood barrier

Near- immediate peak plasma concentrations

Crack cocaine

Cocaine HCl is processed to a base by adding ammonia or baking soda

300 mg dose sells for $5 to $10

Usually smoked, but can also be injected

Cocaethylene

Produced in the body when alcohol is ingested before cocaine

18 - 25- fold increase over cocaine alone in risk of immediate death

Half-life is 3 to 5 hours

DSM-IV Cocaine-related disorders

Cocaine use disorders

Cocaine dependence
Cocaine abuse

Cocaine-induced disorders

Cocaine intoxication
Cocaine withdrawal
Cocaine intoxication delirium
Cocaine-induced psychotic disorder with hallucinations

Cocaine-induced disorders, continued

Cocaine-induced psychotic disorder with delusions

Cocaine-induced mood disorder

Cocaine-induced anxiety disorder

Cocaine-induced sexual dysfunction

Cocaine-induced sleep disorder

Cocaine-induced disorder, not otherwise specified

DSM-IV 292.89 Cocaine Intoxication

A. Recent use of cocaine.

B. Clinically significant maladaptive behavioral or psychological changes (e.g. euphoria or affective blunting; changes in sociability; hypervigilance; interpersonal sensitivity; anxiety, tension, or anger; stereotyped behaviors; impaired judgment; or impaired social or occupational functioning) that developed during, or shortly after, use of cocaine.

DSM-IV Cocaine intoxication (continued)

C. Two (or more) of the following developing during or shortly after cocaine use:

tachycardia or bradycardia

pupillary dilation

elevated or lowered blood pressure

perspiration or chills

nausea or vomiting

evidence of weight loss

psychomotor agitation or retardation

muscular weakness, respiratory depression, chest pain, or cardiac arrhythmias
confusion, seizures, dyskinesieas, dystonias, or coma

DSM-IV Cocaine intoxication (continued)

D. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder

Specify if:

With perceptual disturbances

DSM-IV 292.0 Cocaine Withdrawal

A. Cessation of (or reduction in) cocaine use that has been heavy and prolonged.

B. Dysphoric mood and two (or more) of the following changes, developing within a few hours to several days after Criterion A:

Fatigue
Vivid, unpleasant dreams
Insomnia or hypersomnia
Increased appetite
Psychomotor retardation or agitation

DSM-IV Cocaine Withdrawal (continued)

The symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.

DSM-IV 304.20 Cocaine Dependence

Maladaptive pattern of cocaine use, leading to clinically significant impairment or distress, as manifested by 3 or more of the following, occurring at any time in the same 12-month period:

(1) Tolerance

(2) Withdrawal

(3) Cocaine is often taken in larger amounts or over a longer period than was intended

DSM-IV Cocaine Dependence

(4) persistent desire or unsuccessful efforts to cut down or control substance use
(5) a great deal of time is spent in activities necessary to obtain cocaine, use cocaine, or recover from its effects
(6) important social, occupational, or recreational activities are given up or reduced because of cocaine use
(7) use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by cocaine.

DSM-IV Cocaine Dependence: course specifiers

Early full remission

Early partial remission

Sustained full remission

Sustained partial remission

In a controlled environment

(On agonist therapy)

DSM-IV Cocaine abuse

A. A maladaptive pattern of cocaine use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occuring within a 12-month period.

DSM-IV Cocaine abuse, continued

(1) recurrent cocaine use resulting in a failure to fulfill major role obligations at work, school, or home

(2) Recurrent cocaine use in situations in which it is physically hazardous

(3) Recurrent cocaine-related legal problems

DSM-IV Cocaine abuse, continued

(4) Continued cocaine use despite having a persistent or recurrent social or interpersonal problem caused or exacerbated by its use.

B. The symptoms have never met the criteria for Substance Dependence for this class of substance.

Psychiatric Complications

>50% of cocaine abusers meet criteria for another current DSM disorder

29% have a current alcohol use disorder

62% have a lifetime alcohol use disorder

Concurrent depressive disorders (10 - 50%)

Attention-deficit disorder (35 % met childhood criteria)

Psychiatric Complications

Cocaine-induced psychosis

Schizophrenia

Post-traumatic stress disorder

Personality disorders

Panic disorder

Cocaine-Related Medical Complications

Direct results of cocaine:

Myocardial ischemia
Cardiac arrhythmias
Seizures
Cerebral hemorrhage
CVAs and TIAs
Respiratory paralysis
Pneumonitis

Hyperpyrexia
Migraine-like headaches
Rhabdomyolysis
ARF, liver dysfunction, DIC
Weight loss
Intestinal ischemia

Medical complications: Adulterants

HIV/AIDS/Hepatitis

Increased # of injections
Needle sharing
Unprotected sexual intercourse
High number of sexual partners

Obstetric Complications

Spontaneous abortion
Pre-term labor
Placental abruption
Developmental abnormalities
Difficulty with attention

Cocaine: Assessment

Initial evaluation includes:

History (including DSM criteria)

Physical exam

Consider: CBC, Chemistry profile, urinalysis

Urine (and/or blood) drug screen

Cocaine Overdose

Advanced cardiorespiratory distress / seizures

Life support, thiamine, glucose, Narcan

Myocardial ischemia

Benzodiazepines

Oxygen, nitrites, calcium channel blockers

Hypertension

Calcium-channel blockers (avoid propranolol)

Cocaine intoxication

Assurance in a calm, nonthreatening environment

Antipsychotics such as haloperidol or risperidal for psychosis

Use with caution as they lower the seizure threshold

MAOIs are contraindicated

block cocaine degradation

Cocaine Withdrawal

Limited pharmacological interventions

Benzodiazepines may ameliorate early phase symptoms, but high abuse potential

Monitor for suicidality and persisting depressive symptoms

Pharmacological Treatment of Cocaine Dependence

Many agents were promising in open-label trials

Dopamine agonists:

amantadine,

bromocriptine

MAOIs

mazindol

methylphenidate

pemoline

But not efficacious in placebo-controlled trials

Neurotransmitter precursors

tyrosine, tryptophan

Carbamazepine
Antidepressants:

desipramine

fluoxetine

Ongoing clinical trials

Bupropion

Olanzapine

Naltrexone

Buprenorphine

Talking Therapies

Cognitive-Behavioral therapy

Desensitization

Community reinforcement

Motivation enhancement

Twelve-step facilitation

Cocaine: Summary

Cocaine is a naturally occurring plant product that can be highly addictive

Cocaine intoxication and withdrawal include multiple medical and psychological complications

Cocaine dependence responds to treatment with psychotherapy.

Pharmacotherapies are under development.