1 . The first wave of cocaine use in the United States began during the
| A) | | late 1600s. |
| B) | | late 1800s. |
| C) | | 1940s and 1950s. |
| D) | | 1980s. |
HISTORY AND BACKGROUND OF COCAINE USE
Cocaine was first isolated and synthesized in 1859 in
Germany, and its medicinal effects were first documented in the 1880s[13,14]. Among the proponents of cocaine during this period was Sigmund Freud,
who initially lauded the use of cocaine to treat a variety of conditions (most of which he
retracted in 1887), including depression, alcoholism, and morphine addiction, in an 1884
paper titled On Cocaine. The surgeon William Halstead
also utilized the drug for its local anesthetic effects [13,14]. Both men developed
documented cocaine addictions. In 1886, the soft drink Coca-Cola, which contained cocaine
and caffeine, was introduced. The ability of cocaine to reduce hunger, fatigue, and the need
for sleep was highly valued during the industrial revolution in the late 19th century, and
its use was encouraged to promote worker productivity[13,15]. The demand for
cocaine skyrocketed during this period; the pharmaceutical company Merck produced 0.75
pounds of cocaine in 1883 and 158,352 pounds in 1884[9,12]. Cocaine was widely
available during this period in cigarettes, inhalers, candy, elixirs, solutions, and
over-the-counter products, as well as in wine and soft drinks[13,15]. Use of cocaine eventually reached epidemic proportions. In 1910,
President Taft declared cocaine to be a public enemy, and strict controls were enacted at
the state level[9,15]. Cocaine was removed from the Coca-Cola
formulation in 1903, and the passage of the Harrison Narcotic Act in 1914 severely
restricted the manufacture, distribution, and sale of cocaine in the United States. Cocaine
use plummeted and remained very low for the next six decades[9,15].
2 . During the industrial revolution, cocaine was highly valued for its ability to
| A) | | increase appetite. |
| B) | | reduce the need for sleep. |
| C) | | produce mind-altering effects. |
| D) | | None of the above |
HISTORY AND BACKGROUND OF COCAINE USE
Cocaine was first isolated and synthesized in 1859 in
Germany, and its medicinal effects were first documented in the 1880s[13,14]. Among the proponents of cocaine during this period was Sigmund Freud,
who initially lauded the use of cocaine to treat a variety of conditions (most of which he
retracted in 1887), including depression, alcoholism, and morphine addiction, in an 1884
paper titled On Cocaine. The surgeon William Halstead
also utilized the drug for its local anesthetic effects [13,14]. Both men developed
documented cocaine addictions. In 1886, the soft drink Coca-Cola, which contained cocaine
and caffeine, was introduced. The ability of cocaine to reduce hunger, fatigue, and the need
for sleep was highly valued during the industrial revolution in the late 19th century, and
its use was encouraged to promote worker productivity[13,15]. The demand for
cocaine skyrocketed during this period; the pharmaceutical company Merck produced 0.75
pounds of cocaine in 1883 and 158,352 pounds in 1884[9,12]. Cocaine was widely
available during this period in cigarettes, inhalers, candy, elixirs, solutions, and
over-the-counter products, as well as in wine and soft drinks[13,15]. Use of cocaine eventually reached epidemic proportions. In 1910,
President Taft declared cocaine to be a public enemy, and strict controls were enacted at
the state level[9,15]. Cocaine was removed from the Coca-Cola
formulation in 1903, and the passage of the Harrison Narcotic Act in 1914 severely
restricted the manufacture, distribution, and sale of cocaine in the United States. Cocaine
use plummeted and remained very low for the next six decades[9,15].
3 . The resurgence of cocaine use in the late 1960s coincided with
| A) | | the first isolation and synthesis of cocaine. |
| B) | | the marketing of crack, a new form of cocaine. |
| C) | | decreased availability of heroin in the United States. |
| D) | | tighter regulatory control and decreased use of amphetamines. |
HISTORY AND BACKGROUND OF COCAINE USE
Cocaine use did not experience a resurgence until the late
1960s, coinciding with the tighter regulatory control and decreased use of amphetamines
[12,16]. The seriousness of cocaine abuse and dependence was discounted in the
1960s and 1970s, and little effort was made to understand the mechanism of cocaine addiction
and its treatment, partially because heroin addiction was seen as the most significant
drug-related public health concern[17]. The
introduction, widespread use, and substantial morbidity and mortality of freebase and crack
cocaine in the early 1980s alerted scientists and clinicians of the urgency in understanding
the nature of cocaine addiction and in developing effective treatments.
4 . Freebase is a form of cocaine manufactured by
| A) | | combining cocaine with heroin. |
| B) | | treating cocaine with hydrochloric acid. |
| C) | | removing the hydrochloride base of processed cocaine. |
| D) | | dissolving cocaine hydrochloride in water, adding baking soda, then heating. |
HISTORY AND BACKGROUND OF COCAINE USE
The increase in cocaine use in the 1980s correlated with the
introduction of new forms of the drug. When cocaine is treated with hydrochloric acid (HCl),
it becomes cocaine HCl, which is highly soluble in water and highly lipophilic. Until the
late 1970s, this was the predominant illicit form[9]. Cocaine HCl may be administered intranasally, mixed with water and used
intravenously, or combined with heroin and injected, which is referred to as a
"speedball"[5,9]. Freebase cocaine is a highly pure form
created by removing the hydrochloride base and is not water soluble. Unlike cocaine in the
powdered hydrochloride form, which is destroyed by heat, freebase is smokable. Crack cocaine
is made by dissolving cocaine HCl in water, mixing in baking soda, and heating the mixture
to create a hard substance that is cut into "rocks"[12]. In the early 1980s, cheap and readily available crack cocaine was
introduced, resulting in a rapidly escalating number of regular users and addicts[9].
5 . In 2021, how many Americans were classified as dependent on or abusing cocaine?
| A) | | 500,000 |
| B) | | 1.4 million |
| C) | | 5 million |
| D) | | 25 million |
EPIDEMIOLOGY AND DEMOGRAPHICS OF COCAINE ABUSE AND DEPENDENCE
In 2021, 4.8 million Americans (1.7%) had used cocaine within
the past year, with 1.4 million individuals 12 years of age or older classified as dependent
on or abusing cocaine [18]. Every day, 1,310
people use a cocaine product for the first time, with 60% of initiates 18 to 25 years of age
and 39% of initiates 26 years of age or older[18]. Between 2002 and 2021, the number of annual initiates of cocaine declined
from 1,032,000 to 478,000[18]. Older estimates
in the United States have shown that cocaine is used primarily by young men, who outnumber
female users by approximately 2 to 1[19].
Past-year cocaine use rates do not differ significantly by race/ethnicity, except among
multiracial (defined as more than one race, but not Hispanic or Latino) individuals, of whom
3.2% reportedly used cocaine in the past year [18]. Overall, environmental and social factors (e.g., approached by someone
selling cocaine, parental involvement, religious beliefs, scholastic environment) account for
risk of cocaine use considerably more than race or ethnicity[19].
6 . Populations at higher risk for cocaine-induced toxicity include all of the following, EXCEPT:
| A) | | Infants |
| B) | | Adolescents |
| C) | | Pregnant women |
| D) | | Patients with liver disease |
EPIDEMIOLOGY AND DEMOGRAPHICS OF COCAINE ABUSE AND DEPENDENCE
Certain populations are more vulnerable to cocaine-induced
toxicity, primarily due to their inefficient capacity for metabolism and clearance of the drug
and its breakdown products. These include the elderly, infants, fetuses, pregnant women, and
patients with liver disease[13]. Other factors
that influence individual variation in susceptibility to cocaine-induced toxicity include age,
sex, body mass, hepatic and renal function, drug-drug interactions, and genetic
variability[21]. Black American users are
more likely than non-black users to experience rhabdomyolysis, excited delirium, and changes
in cardiac rhythm[13].
7 . Male cocaine abusers are more likely than women to
| A) | | have antisocial personality disorder. |
| B) | | experience cardiovascular effects of the drug. |
| C) | | be severely dependent or to abuse other drugs. |
| D) | | be diagnosed with paranoid personality disorder. |
EPIDEMIOLOGY AND DEMOGRAPHICS OF COCAINE ABUSE AND DEPENDENCE
Gender differences in the effects of cocaine have also been
observed. Men who use cocaine experience higher blood concentration levels and greater drug
effect than women, and women are more sensitive to the cardiovascular effects than men[12,22]. Women presenting for treatment of cocaine dependence are more likely than
males to be severely dependent, to abuse other drugs, to have a briefer period of abstinence,
and to have childhood histories of physical or sexual abuse[17]. Gender differences in comorbidity have also been found, with female
cocaine abusers more likely to have major depression and male cocaine abusers more likely to
have antisocial personality disorder[17].
8 . Action involving which neurotransmitter is the most important in producing the reinforcing effects of cocaine?
| A) | | Choline |
| B) | | Serotonin |
| C) | | Dopamine |
| D) | | Norepinephrine |
Cocaine's specific mechanism of action involves increasing
the synaptic transmission of dopamine, serotonin, and norepinephrine by interaction with
plasma membrane transporters to block presynaptic reuptake. Action involving the dopamine
transporter is the most important in producing the reinforcing effects, which lead to
dependence [23]. The increased postsynaptic
dopamine activity following its blocked presynaptic reuptake forms the basis of cocaine
action[17].
9 . The basis of cocaine's mechanism of action is
| A) | | stimulating the release of dopamine. |
| B) | | decreased transmission of serotonin and norepinephrine. |
| C) | | increased postsynaptic dopamine activity following its blocked presynaptic reuptake. |
| D) | | None of the above |
Cocaine's specific mechanism of action involves increasing
the synaptic transmission of dopamine, serotonin, and norepinephrine by interaction with
plasma membrane transporters to block presynaptic reuptake. Action involving the dopamine
transporter is the most important in producing the reinforcing effects, which lead to
dependence [23]. The increased postsynaptic
dopamine activity following its blocked presynaptic reuptake forms the basis of cocaine
action[17].
10 . The effects of cocaine are felt most rapidly and intensely when administered
| A) | | by smoking. |
| B) | | intranasally. |
| C) | | cutaneously. |
| D) | | intravenously. |
Cocaine can be absorbed through any mucous membrane.
Different routes of cocaine delivery into the body produce different patterns and levels of
blood cocaine concentration. Intranasally administered cocaine is absorbed and distributed
into the body gradually, while the onset of effect is rapid when smoked or injected. The
effect of cocaine is experienced most rapidly and intensely when smoked, with an onset of
effects typically occurring within 8 to 10 seconds; thus, cocaine is most addictive when
smoked [23]. Injected cocaine takes twice as
long to enter the brain (i.e., 16 to 20 seconds), and snorted cocaine begins to act in three
to five minutes[12]. The lungs are the most
rapid and efficient cocaine delivery modality because of the large surface area of
absorption and rapidity of arterial circulation to the brain[9,29].
11 . Peak plasma levels of cocaine occur how long after intranasal ingestion?
| A) | | 2 to 4 minutes |
| B) | | 20 to 40 minutes |
| C) | | 2 to 4 hours |
| D) | | 12 to 14 hours |
Peak plasma levels of cocaine occur 20 to 40 minutes
following intranasal ingestion, with a typical concentration of 100–500 mcg/L. Toxicity is
rarely seen at this dose level. Plasma half-life ranges from 31 to 82 minutes, with a mean
of 38 minutes[13].
12 . Physiologic signs of acute cocaine ingestion include
| A) | | decreased arterial pressure. |
| B) | | increased locomotor activity. |
| C) | | decreased myocardial oxygen demand. |
| D) | | hypothermia secondary to vasodilatation. |
EFFECTS OF COCAINE USE
| Type of Use | Psychologic Symptoms | Physiologic Signs |
|---|
| Acute ingestion |
| Euphoria | | Heightened self-confidence, well-being, energy, and alertness | | Restlessness | | Reduced need for food | | Insomnia |
|
| Elevated arterial pressure | | Increased heart rate and respiration | | Coronary vasoconstriction | | Increased myocardial oxygen demand | | Hyperthermia secondary to cutaneous vasoconstriction | | Increased locomotor activity |
|
| Chronic ingestion |
| Dysphoria | | Agitation | | Anxiety and panic | | Loss of concentration | | Diminished libido | | Paranoia | | Visual or auditory hallucinations | | Delusions |
|
| Pacing | | Restlessness | | Hyperactivity | | Grinding of teeth | | Mood lability | | Insomnia |
|
13 . Cerebrovascular complications of chronic cocaine use are the result of its effects on noradrenergic neurotransmission and include
| A) | | vasodilatation. |
| B) | | increase in blood flow. |
| C) | | inflammation of blood vessel walls. |
| D) | | All of the above |
Drugs that increase brain monoamine concentration also
have the potential to elevate peripheral monoamine activity [28]. Cocaine stimulates dopamine and alpha-
and beta-adrenergic receptors in the CNS and in the peripheral nervous system, which is
the underlying basis of the adverse systemic effects of this drug[12,29]. The cerebrovascular complications caused by cocaine are the result of
its effect on noradrenergic neurotransmission and include vasoconstriction and resultant
decrease in blood flow, inflammation of blood vessel walls, and hyperpyrexia[23,29].
14 . Cardiac complications of cocaine use
| A) | | are only the result of chronic administration of the drug. |
| B) | | are rare, as the drug has little affinity for cardiac tissue. |
| C) | | are induced only in those individuals with a positive history for cardiac conditions. |
| D) | | stem primarily from the powerful sympathomimetic properties of the drug. |
Cocaine produces cardiovascular pathology in susceptible
users by altering the myocardium and vasculature in a manner that may eventually manifest
as cardiac disease, hypertension, or atherosclerosis[30]. The cocaine molecule has a high affinity for cardiac tissue, and both
acute and chronic cocaine use can induce a variety of cardiac complications in persons
with a negative history of such conditions, primarily from the powerful sympathomimetic
properties of the drug[28,39]. Specific cocaine-induced cardiac
conditions include myocardial infarction, ischemia, arterial thrombosis, ventricular
tachycardia, ventricular fibrillation, and sudden death. Other cardiac conditions
attributable to cocaine use include dilated cardiomyopathy, hypertension, myocarditis, and
coronary artery occlusion[12,29].
15 . The most common gastrointestinal complication of chronic cocaine use is
| A) | | liver toxicity. |
| B) | | malnutrition. |
| C) | | acute bowel perforation. |
| D) | | gastroduodenal ulceration. |
Malnutrition is the most common gastrointestinal (GI)
complication from cocaine use. This is influenced by the adverse effect of cocaine on food
and beverage consumption, taste, and nutrient absorption. Other GI complications from
cocaine use are less common and include gastroduodenal ulceration, acute bowel
perforation, liver toxicity, and pancreatic and endocrine disease [12].
16 . In the treatment of cocaine use disorder, community reinforcement approaches
| A) | | are relatively low cost and require little labor or commitment. |
| B) | | provide competing reinforcement through the development of a positive lifestyle. |
| C) | | aim to increase abstinence by forcing the individual to become isolated in an effort to remove environmental cues. |
| D) | | None of the above |
TREATMENT OF COCAINE USE DISORDER
Community reinforcement approaches (CRAs) are
biopsychosocial interventions designed to engage and change the lifestyle of the drug
abuser by addressing the role of environmental cues and alternative reinforcers in
influencing behavior. The theoretical basis of the CRA is that substance abuse is
maintained by substance-related reinforcers as well as by the absence of competing
alternative reinforcers. The primary goal of the CRA is to build and strengthen
relationships, recognize appropriate leisure activities, and identify vocational interests
of the patient to provide competing reinforcement with cocaine use and the drug-using
lifestyle [64]. CRA aims to increase
abstinence by increasing or highlighting the opportunity cost of relationships and social
support the patient stands to lose through drug use[58]. In addition to integrating cognitive-behavioral and, in some cases,
pharmacologic approaches, CRA may also include the use of vouchers, whereby tokens are
given to the patient for producing substance-free urine samples, which are then used to
purchase goods and services desired by the patient.
A review of four studies utilizing CRA with patients with
cocaine use disorder found evidence that CRA employing abstinence-contingent incentives in
the form of vouchers was more effective in promoting abstinence than CRA using
noncontingent incentives and usual care. Patients assigned to CRA incorporating
abstinence-contingent incentives experienced a greater reduction in disease severity as
measured by the Addiction Severity Index than comparison groups[64]. Despite early, promising reports of CRA
with patients with alcohol use disorder and evidence that patients receiving CRA have
demonstrated more favorable drug use outcomes than patients receiving standard outpatient
counseling, CRA is seldom used because of the relatively high cost and labor
intensity[53,65].
17 . When used for patients with cocaine use disorder, motivational-enhancement therapy
| A) | | seems to be more effective in those with low initial levels of motivation. |
| B) | | tends to result in fewer total days of cocaine use, but a greater risk for relapse. |
| C) | | strives to build and strengthen relationships and establish appropriate leisure activities. |
| D) | | helps patients build internal motivation through the resolution of issues related to past trauma. |
TREATMENT OF COCAINE USE DISORDER
Motivational interventions for substance abuse stem from
the theory that targeting and enhancing motivation to quit drugs will increase positive
outcome; positive outcome is increased when motivation comes internally rather than when
it is externally imposed. Specifically, motivational-enhancement therapies (MET) are based
on the Transtheoretical Stages of Change Theory, which postulates that patients pass
through a series of stages of thought, planning, and action in the process of behavior
change [66]. MET is intended to enhance
motivation and commitment to change, activate patient resources, and facilitate movement
along the readiness-to-change spectrum[67]. MET helps patients build internal motivation through the resolution of issues related
to ambivalence. The therapeutic approach is characterized by nonconfrontive, nonjudgmental
interviewing that helps the patient consider the pros and cons of change. MET also strives
to enhance patient self-efficacy[66]. MET
seems to be more effective in patients with low initial levels of motivation when used for
patients with cocaine use disorder. It tends to result in less relapse to cocaine use and
fewer total days of cocaine use[68].
18 . It has been hypothesized that disulfiram may be a helpful drug for the treatment of cocaine use disorder based on what action?
| A) | | Decrease in available dopamine |
| B) | | Inhibition of aldehyde dehydrogenase |
| C) | | Increase in the metabolite acetaldehyde |
| D) | | Inhibition of the enzyme that converts dopamine to norepinephrine |
TREATMENT OF COCAINE USE DISORDER
Disulfiram is an oral medication used for decades as
aversive therapy for alcohol dependence. It acts by inhibiting aldehyde dehydrogenase,
thereby increasing the amount of the toxic alcohol metabolite acetaldehyde. Disulfiram
also inhibits the enzyme that converts dopamine to norepinephrine. This increase in
dopamine has been hypothesized to make disulfiram a helpful drug for cocaine use disorder.
Several studies have been performed with patients with cocaine use disorder, and
researchers have found that, relative to placebo, use of disulfiram results in decreased
craving for cocaine, increased dysphoria in patients who have ingested cocaine
concurrently, decreased quantity and frequency of cocaine use, and reduced number of
cocaine-positive urine samples. These results are encouraging. However, additional trials
are needed to determine the optimal dose and duration of treatment [24,80,90]. A small 2016
trial sought to determine if supplementing CBT with disulfiram would enhance abstinence
outcomes but found no benefit with addition of the drug[91].
19 . Vaccine therapy for cocaine use disorder has been considered in part due to
| A) | | its ability to eliminate cravings. |
| B) | | disappointing results of pharmacotherapy trials that targeted reward pathways. |
| C) | | its protection against stimulant drugs that are structurally distinct from cocaine. |
| D) | | the lack of variation in antibody formation across cocaine-dependent individuals. |
TREATMENT OF COCAINE USE DISORDER
Pharmacotherapy for cocaine use disorder targets brain
neuronal pathways, whereas immunotherapy for cocaine use disorder acts peripherally to
inhibit the effects of cocaine by blocking or delaying entry of the cocaine molecule into
the brain [24]. The impetus for the
development and evaluation of biologic therapies for cocaine use disorder stems, in part,
from the potential side effects and disappointing results of pharmacotherapy trials
targeting reward pathways that mediate the addictive effects of cocaine[23].
20 . A triphasic abstinence syndrome from heavy cocaine use has been identified. Phase two is characterized by
| A) | | a peak in feelings of paranoia. |
| B) | | episodic craving that is gradually extinguished. |
| C) | | prolonged anhedonia, impaired motivation, and an increased risk for relapse. |
| D) | | acute withdrawal symptoms, including depression, tachycardia and unstable blood pressure. |
Phase two can last one to ten weeks, during which time
patients are likely to experience prolonged anhedonia, impaired motivation, dysphoria, and
craving. It is during this period that patients are at highest risk of relapse. Outpatients
are especially vulnerable to environmental cue-induced triggers for cocaine use. Persons,
places, and things associated with cocaine use stimulate vivid recollection and
cocaine-induced euphoria that, when contrasted with the ongoing dysphoria, can make resumption
of use irresistible. If relapse occurs during this phase, it can activate the vicious cycle of
heavy use, attempts to quit, and relapse[17].
