Running head: COCAINE USE DISORDER 1

The Role of the Nucleus Accumbens in Cocaine Use Disorder

Anastasia Platoff

Lesley University

Author Note

The author is a master’s degree candidate in the Counseling and Psychology Program,

Department of Counseling and Psychology, Lesley University, Cambridge, MA.

This was paper submitted to Professor Sidney Trantham as partial fulfillment of the

requirements of 16-FA GCOUN.7100.01, Biological Bases of Behavior, December 2, 2016.

Correspondence to the author should be sent to aplatoff@lesley.edu

COCAINE USE DISORDER 2

Abstract

Cocaine use disorder (CUD) is a substance use disorder that currently affects millions of people

worldwide. Cocaine is a powerful stimulant that is derived from the leaves of the coca plant,

indigenous to South America. In the latter half of the 19th century, cocaine was extolled in North

America and Europe for its advantageous effects as a stimulant and its utility as surgical

anesthetic. The widespread availability of cocaine led to surges in recreational use, which in turn

exposed its high potential for abuse. The history of cocaine in the United States reflects shifting

cultural beliefs about its use and misuse. It was not until 1980 that the American Psychiatric

Association recognized substance use disorders as mental health disorders, rather than a lack of

willpower or an immoral lifestyle choice. However, as brain science has advanced, so have the

definitions of cocaine abuse and addiction. The prevailing theory is that addiction hijacks the

brain’s reward system—notably the mesolimbic dopamine pathway, which projects from the

ventral tegmental area to the nucleus accumbens. Extensive research has confirmed that the

rewarding properties of drugs of abuse are attributed to their effects on dopamine activity in the

nucleus accumbens. Current treatment options for CUD include behavioral therapies (e.g.,

cognitive-behavioral therapy and contingency management), as well as complimentary and

alternative treatments such as self-help groups and mindfulness-based therapy. Hopeful future

treatments include pharmacotherapies. Suggested areas of future research focus on the

development of holistic and culturally appropriate treatment models for CUD.

Keywords: Addiction, assessment, cocaine use disorder, CUD, dopamine, nucleus

accumbens, treatment
COCAINE USE DISORDER 3

The Role of the Nucleus Accumbens in Cocaine Use Disorder

Cocaine is the second most widely consumed illegal drug in the world, following

cannabis (United Nations Office on Drugs and Crime, 2015). It has the highest rates of use in

North America and Western Europe and is used by approximately 14 to 21 million people

worldwide (UNODC, 2015). Cocaine is a powerful central nervous system (CNS) stimulant that

can have a number of adverse health effects, including acute toxic effects (e.g., overdose;

accidental injury; and violence), dependence, cardiovascular disease, blood-borne infections, and

mental disorders (Pomara et al., 2012). Cocaine use disorder (CUD) is substance use disorder

characterized by recurrent use of cocaine that causes clinically significant functional impairment

(American Psychiatric Association, 2013). The classification of a severe substance use disorder

is synonymous with the term addiction (Volkow, Koob, & McLellan, 2016). The diagnosis of

CUD may refer to individuals who present with symptoms of cocaine dependence, abuse, or

addiction. The clinical severity of a CUD diagnosis will be reflected in its specification as mild,

moderate, or severe. The development of drug dependence or addiction is often associated with

two adaptations—tolerance: a decrease in the effects of the drug over time, and withdrawal: a

strong physiological response when the drug is absent (Hasin et al., 2013).

Cocaine can be consumed in various preparations—e.g., coca leaves; cocaine

hydrochloride (powdered cocaine); and cocaine alkaloids (freebase and crack cocaine)—that

vary in potency due to speed of onset and differing levels of purity (APA, 2013). Routes of

administration include intranasal (“snorting”), inhalation (smoking) or intravenous (injecting).

Initial effects of cocaine include: enhanced energy and confidence; a feeling of euphoria;

hyperactivity; alertness, and, at times, sensory hallucinations. High doses or prolonged use of
COCAINE USE DISORDER 4

cocaine can produce negative effects such as insomnia, paranoia, nervousness, psychomotor

agitation, seizures, and dysphoria (APA, 2013; Gootenberg, 2015).

In 2014, it was estimated that 1.5 million Americans age 12 or older were current users of

cocaine, with an estimated 913,000 meeting criteria for CUD (Center for Behavioral Health

Statistics and Quality, 2015). Estimated prevalence of CUD is higher among males (0.4%) than

females (0.1%). In the U.S., the highest rates of use are found among 18- to 29-year olds, and the

lowest rates are found among 45- to 64-year-olds. Recent mental health survey data from the

World Health Organization (WHO) indicate that the United States is an outlier in lifetime

cocaine use, with 16% of U.S. respondents reporting that they had used cocaine at least once,

compared to approximately 4.0% in Colombia, Mexico, Spain, and New Zealand, and even

lower proportions in countries in the Middle East, Africa, and Asia. In general, high rates of drug

use are associated with more affluent countries, and the U.S., despite harsh illicit drug policies,

stands out with the higher levels of drug use (Degenhardt et al., 2008). Although worldwide rates

of cocaine use have declined in the last decade, cocaine use in the U.S. and other Western

countries remain relatively high and stable (CBHSQ, 2015). These statistics are concerning,

given the severe and wide-ranging consequences that drug abuse has on individuals, families,

communities, and societies.

Cocaine is an alkaloid that is extracted from the leaves of the coca plant. The coca plant

is indigenous to Central and South America. For thousands of years, the plant has grown wild in

hot and humid tropical climates, primarily in the regions that comprise the countries of

Colombia, Peru, and Bolivia. For millennia, indigenous peoples in Western South America have

used coca leaves for religious, medicinal, and functional reasons (Petersen & Stillman, 1977).

Native Peruvians chewed the leaves as part of their religious rituals. Since this practice was
COCAINE USE DISORDER 5

known to increase energy and reduce hunger and thirst, the Spanish Conquistadors gave coca

leaves to enslaved Peruvians in order to increase their silver mining (Robinson and Adinoff,

2016). The coca plant was not cultivated in Europe until the emergence of heated greenhouses in

the 1700’s (Robinson & Adinoff, 2016). In mid-19th century Europe, cocaine was successfully

isolated as the active ingredient in the coca leaf. The knowledge of its use as a stimulant and

local anesthetic was disseminated and, for the following two decades, cocaine was valued and

praised among Western medical communities and pharmaceutical companies. It was routinely

extolled for its “non-addictive properties” and “its potential usefulness in weaning people off the

dangerous ‘morphine habit’” (Robinson & Adinoff, 2016, p. 4). Sigmund Freud was one of the

notable figures who claimed that cocaine was a non-addictive substance that could provide a host

of physical and psychological benefits. However, “this era of unrestrained medical enthusiasm

was short-lived” (Arif, 1987, p. 1).

In 1863, French chemist Angelo Mariani created Vin Marian—a drink made from coca

leaves and wine. It became hugely popular and was said to have been used by literary figures

such as Jules Verne, Arthur Conan Doyle, and Alexander Dumas (Hamblin, 2013). In 1886, Dr.

John Pemberton was inspired to concoct his own version in Atlanta, Georgia. His hope was to

create a tonic that would cure the morphine addiction he developed after being injured during the

Civil War. The tonic, Pemberton’s French Wine Coca, was made from a combination of kola

nuts, wine, and coca leaves and was marketed as a panacea. 34 years before the 18th Amendment,

Atlanta legislature enacted the early prohibition of alcohol, and Pemberton decided to replace the

alcohol in his drink with a caffeinated, saccharine syrup. He called this new product Coca-Cola.

It started being sold by the bottle in 1899. This widespread availability of cocaine led to surges in

its recreational use, which in turn catalyzed public (and racialized) hysteria about its unregulated
COCAINE USE DISORDER 6

use (see Hamblin, 2013). In 1903, in response to heightening social pressure, the Coca-Cola

company started to chemically extract the ecgonine alkaloid, the psychoactive element of coca,

from their beverage (Hamblin, 2013; Robinson & Adinoff, 2016).

The history of cocaine in the United States constitutes interwoven stories of medical,

religious, moral, legal, and political influence. 19th-century American industrialization had

significant effects on the conceptualization of cocaine and its use/misuse. With the onset of

industrialization, the dominant culture ascribed value to individual productivity and wealth, and

concomitantly condemned the ‘addict,’ who was perceived as an unproductive and dangerous

pariah (Robinson & Adinoff, 2016). Similar to the Spanish Conquistadors’ provision of coca

leaves to Peruvian slaves, American industrialists and plantation owners supplied cocaine to

Black workers in an effort to increase productivity, yet “the association of the drug with racial

minorities resulted in racialized, zealous accounts of minorities (i.e., ‘negro cocaine fiends’)

driven mad by the drug” (Robinson & Adinoff, 2016, p. 7). When racism became enmeshed in

conceptions of cocaine, public disapproval and criminalization shortly followed.

The first federal U.S. drug prohibitions began with the Harrison Narcotics Act of 1914,

which significantly restricted the availability of coca and cocaine. Access was regulated under

federal law to professionals in the medical field (Robinson & Adinoff, 2016; Petersen &

Stillman, 1977). More serious restrictions were established under the Jones-Miller Act of 1922

when the Federal Narcotics Control Board (FNCB) was created to oversee the import/export of

drugs and curtail recreational use. Through this Act, cocaine became legally classified as a

narcotic. In the early 1900’s, “nothing seemed more ‘all-American’ than imported Andean coca

leaf… thirty years later, coca leaf was deemed a nasty base addiction of remote Andean Indians

and no one remembered its domesticated phase” (Gootenberg, 2009, p. 36).

COCAINE USE DISORDER 7

The U.S. saw a major decrease in cocaine consumption until the drug reemerged in the

1960’s (Pomara et al., 2012). Cocaine then burgeoned in 1970’s disco culture as the most

expensive and glamorous drug of choice (Gootenberg, 2012). President Nixon had declared a

War on Drugs in 1969, but U.S. interception efforts were predominantly focused on heroin and

marijuana. Geopolitical shifts throughout the Cold War had made it easier and more profitable

for Colombian and other drug cartels to smuggle cocaine into the U.S., and they did so in

massive quantities through complex transportation networks (Gootenberg, 2012). President

Reagan initiated his own War on Drugs in 1982. Crack cocaine—the crystallized, smokable form

of the drug—first appeared in the U.S. in 1985 (Gootenberg, 2012). It was much cheaper than its

powdered counterpart, and it became increasingly prevalent in lower-income areas and

communities of color. By the middle of the decade, “cocaine had affected the lives of some 22

million users” (Gootenberg, 2012, p 166). The Anti-Drug Abuse Act of 1986 initiated punitive

and discriminatory laws for the possession and trafficking of crack cocaine (i.e., the 100:1

sentencing disparity and new mandatory minimums). “By 2004, 84% of those imprisoned for

crack were black and 9% Latino” (Gootenberg, 2015, p. 104). An effort at amelioration was

made through the Fair Sentencing Act of 2010, which reduced the crack versus powder

sentencing disparity to a 16:1 ratio.

Reagan’s drug war has been correlated with rising incarceration rates and racial

disparities in arrests and sentencing for drug offenses (Beckett, Nyrop, Pfingst, & Bowen, 2005).

Similar to antecedent American representations of drug addiction, the cultural discourse and

imagery around the crack epidemic were highly racialized. The violence and poverty were real,

but the surrounding media mythos stood in stark contrast to news stories on White recreational

users of cocaine powder, who were often portrayed as victims—in need of support, but capable
COCAINE USE DISORDER 8

of recovery. In the 1980’s and 1990’s, the meanings of cocaine use were re-created in the images

“crack heads” and their “crack babies”—the embodiment of an epidemic, essentialized as poor,

urban, and nonwhite (Beckett et al., 2005). The “Just Say No” campaign purported values of

self-determination and independence that implicitly framed addiction as a choice of hedonism

(Volkow et al., 2016).

In the first edition of the DSM (1952), ‘Alcoholism and Drug Addiction’ was classified as

a ‘Sociopathic Personality Disturbance.’ It was not until the 1980 publication of the DSM-III that

substance use disorders were recognized as mental health disorders (Robinson & Adinoff, 2016).

As psychology and brain science advanced, so too did the definitions of addiction. Nonetheless,

the history of cocaine in the U.S. reflects enduring discord between scientific discovery and

cultural belief.

At present, the pharmacological properties of cocaine are well known, as are its

behavioral effects (Robinson & Adinoff, 2016). In the current medical model, addiction is

understood as a chronic disease that causes significant changes in brain structure and function

(MacDonald, 2011). The contemporary research on CUD emphasizes the role of the nucleus

accumbens in the development of cocaine dependence and addiction. Stimulant drugs work by

either blocking the reuptake of dopamine or by reversing the dopamine transporter so that,

instead of producing reuptake, dopamine is released (Calipari & Ferris, 2013; Pomara, 2012). In

either case, this results in surges of the neurotransmitter dopamine, as well as the other

monoamines, norepinephrine and serotonin (Robinson & Adinoff, 2016). An extensive body of

research has robustly confirmed that the reinforcing and rewarding properties of cocaine are

attributed to their influence on dopamine activity in the nucleus accumbens (Calipari et al., 2016;
COCAINE USE DISORDER 9

Berridge & Kringelbach, 2015; Koob & Volkow, 2010; Wheeler & Carelli, 2009; Yager et al.,

2015).

The brain reward regions, as illustrated in Figure 1 (Dubuc, n.d.), include dopaminergic

neurons in the ventral tegmental area as well as the limbic regions to which they project (Russo,

2010). In neuropsychological research on addiction, reward can be distinguished by the

representations of “wanting” (incentive salience) and “liking” (hedonic responses). Anselme and

Robinson (2016) posit that dopamine transmission in the nucleus accumbens controls the

experience of “wanting” (but not “liking”) in the expression of addiction-related behaviors.

Further confirmation of the dissociation between “liking” and “wanting” is found in studies that

show enhanced drug-seeking in cocaine abusers despite their tolerance to the euphoric effects of

the stimulant (Berridge & Kringelbach, 2015). Individuals with CUD may be preoccupied with

thoughts of cocaine and compulsively search the floor for white specks although they experience

accompanying distress and a notable absence of pleasure.

CUD involves a Pavlovian-instrumental learning process in which repeated cocaine

exposure causes dopamine cells to “stop firing in response to the reward itself and instead fire in

an anticipatory response to the conditioned stimuli [i.e., ‘cues’] that predict the delivery of the

reward” (Volkow et al., 2016, p. 364). These context-induced cues can stimulate cravings, which

act as potent reinforcers of drug-seeking behavior. Even after years of abstinence from cocaine

use, relapse can result from a failure to extinguish learned associations between cocaine and the

environmental contexts of its use (Calipari et al., 2016; Cruz et al., 2014; Saunders, Yager, &

Robinson, 2014).

Studies have shown that repeated cocaine use produces neuroadaptations in the nucleus

accumbens and the ventral tegmental area, wherein receptors become more responsive to cocaine
COCAINE USE DISORDER 10

and its related cues and less responsive to other forms of reinforcement (Conrad et al., 2008;

Koya et al, 2012). The development and persistence of cocaine-seeking behavior is associated

with synaptic plasticity in medium spiny neurons (MSNs) in the nucleus accumbens (Jedynak et

al., 2016; Saunders et al., 2014). Recent research on CUD differentiates MSNs activity in the

shell and core components of the nucleus accumbens (Wheeler & Carelli, 2009; Everitt &

Robbins, 2005). Neurons in the nucleus accumbens shell are smaller and less spiny than those in

the core, and the projection patterns of these subdivisions reflect their distinct functions in CUD.

The nucleus accumbens core is associated with the processing of conditioned stimuli, whereas

the shell is significant in the processing of unconditional stimuli (Everitt & Robbins, 2005).

Dopamine innervation from the ventral tegmental area to the accumbens shell modulates

motivational salience and contributes to “learned associations between motivational events and

concurrent environment perceptions” (Kalivas & Volkow, 2005, p. 1405). The core is a site that

subsequently mediates the strength of context-reward associations, as well as the expression of

learned behavioral responses to these drug-related cues.

Previous research on dopamine D1 and D2 receptors in the nucleus accumbens has

provided clues about the activation of context-reward associations and the expression of learned

behaviors. Optogenetic stimulation of D1 MSNs has been shown to promote reward, while

stimulation of D2 MSNs has been shown to prompt aversion (Calipari et al., 2016). “Chronic

cocaine exposure dysregulates these D1 signals to both prevent extinction and facilitate

reinstatement of drug seeking to drive relapse” (Calipari et al., 2016, p. 2726). In an in vivo

imaging study, Calipari and her colleagues found that when the D1 signal was eliminated, the

context-reward association no longer existed. These findings suggest that pharmacological

interventions that target selective actions of the D1 and D2 MSNs could “help to eliminate or
COCAINE USE DISORDER 11

attenuate these [context-reward] associations in drug addicted individuals in a way that would

greatly improve treatment outcomes” (Calipari et al., 2016, p. 2730).

The neurotransmitter glutamate is also important in CUD, as its signaling regulates

dopamine cell reactivity and release in the nucleus accumbens and plays a role in the

development of compulsive drug-taking (Jedynak et al., 2016; Kalivas and Volkow, 2005;

Volkow et al., 2016). While dopamine is involved in reinforcement and motivated behaviors, “its

effects are largely modulatory, and it is the glutamatergic inputs that provide the excitatory drive

for these circuits” (Calipari et al., 2016, p. 2729). Source regions of the glutamate include the

prefrontal cortex, amygdala, hippocampus, and thalamus, while the nucleus accumbens receives

dopaminergic inputs from the the ventral tegmental area and the substantia nigra (Yager et al.,

2015). These brain regions are meaningful contributors to CUD. Although a thorough

examination of these areas is outside the scope of this review, it is important to highlight that the

neurobiological underpinnings of substance abuse are not localized, but diffuse and

interconnected.

Everitt and Robbins (2005) elucidate how different structures in this neurological

constellation are functionally and anatomically associated with addictive behaviors. The

hippocampal formation is a major source of glutamatergic afferents, particularly to the nucleus

accumbens shell. The hippocampus is highly involved in encoding contextual details and spatial

configurations of novel events and episodic memories. The amygdala is recruited in the

processing of emotionally significant stimuli and events, including experiences of desire, fear,

and stress. The brain regions that are involved in emotions are highly active during periods of

withdrawal. The amygdala contributes to the anticipation of a reward, stress in response to its

absence, and subsequent feelings of depression, anxiety, and restlessness (Volkow et al., 2016).
COCAINE USE DISORDER 12

The prefrontal cortex interfaces with the nucleus accumbens in situations involving goal-directed

behavior and the attribution of value/salience (Everitt & Robbins, 2005). During phases of

preoccupation and drug craving, functioning in the prefrontal cortex is decreased, whereas the

cingulate cortex and temporal lobe (including the amygdala and hippocampus) are activated. In

CUD, this pattern of connectivity leads to an inability to balance the desire for cocaine with the

will to abstain (Everitt & Robbins, 2005; Volkow et al., 2016).

The Diagnostic and Statistical Manual of Mental Disorders (5th ed.; APA, 2013)

classifies CUD as a stimulant-related disorder—one of nine types of Substance-Related and

Addictive Disorders. In order to meet diagnostic criteria for CUD, an individual must have a

pattern of cocaine use “leading to clinically significant impairment or distress, as manifested by

at least two of [eleven identified criteria] within a 12-month period” (APA, 2013, p. 561). These

criteria include using cocaine in larger amounts or over a longer period of time than intended; a

persistent desire or unsuccessful attempts to control use; craving for the drug; recurrent cocaine

use despite severe functional impairment caused or exacerbated by its effects; the development

of tolerance; withdrawal that occurs after stopping or reducing use. (For the complete DSM-5

criteria for CUD, see Appendix.)

Physiological and psychological signs of cocaine use may include: tachycardia, weight

loss, psychomotor agitation, impaired judgment, respiratory problems, and perceptual

disturbances. The changes that occur during cocaine intoxication are opposite to those of the

withdrawal phase. After cessation of chronic cocaine use, withdrawal symptoms may include:

bradycardia; dysphoric mood; increased appetite; and psychomotor retardation (APA, 2013).

Cocaine use is often associated with psychiatric comorbidity, e.g., posttraumatic stress

disorder, attention-deficit/hyperactivity disorder, eating disorders, gambling disorder, and

COCAINE USE DISORDER 13

antisocial personality disorder, while stimulant-induced disorders may resemble primary mental

health disorders such as schizophrenia, depressive and bipolar disorders, and generalized anxiety

disorder (APA, 2013; Ford et al., 2009). It is important for diagnosticians to identify whether an

individual’s substance use is primary or secondary, or causal or correlative, in relation to a

mental disturbance (e.g., the distinction between severe CUD with cocaine-induced bipolar

disorder and bipolar disorder with a comorbid CUD). In CUD, co-occurring medical conditions

may vary based on the route of cocaine administration (e.g., respiratory problems in individuals

who smoke crack; increased HIV risk in intravenous users; sinusitis and perforation of the nasal

septum in intranasal users; APA, 2013). CUD frequently co-occurs with other substance use

disorders, especially drugs with sedative properties, which are taken to reduce the unpleasant

side effects of cocaine use.

Screening and assessment tools for drug use and abuse include the: Cocaine Selective

Severity Assessment (CSSA; Ahmadi et al., 2009); Cocaine Craving Questionnaire (CCQ;

Paliwal, Hyman, & Sinha, 2008); Cocaine Experience Questionnaire (CEQ; Gooding et al.,

2013); Addiction Severity Index (ASI; Denis et al., 2016); Semi-Structured Assessment for Drug

Dependence and Alcoholism (SSADDA; Pierucci-Ladha et al., 2005); CAGE-AID

(Couwenbergh et al., 2009); Drug Abuse Screening Test (DAST; Yudko et al., 2007); and

CRAFFT Screening Tool (for children and adolescents; Agley et al., 2015). These instruments

are among those commonly used in research and clinical settings, but only three are specifically

used to measure cocaine use and dependence (the CSSA; CEQ; and CCQ). Additionally, most of

these assessments for substance abuse were developed in light of DSM-IV criteria and thus they

lack reliable or valid diagnostic utility for CUD as it is defined in the DSM-5. Cannizzaro et al.’s

(2014) Neuropsychological Assessment Battery-Screening Module (S-NAB) can be used to

COCAINE USE DISORDER 14

detect cognitive impairments in treatment-seeking cocaine users. This assessment is promising

for CUD treatment retention, as it can help clinicians adapt their treatment methods to better

serve their patients’ specific cognitive strengths and deficits (Cannizzaro et al., 2014).

No single treatment approach is suitable for everyone with a substance use disorder

(National Institute on Drug Abuse, 2012). Cultural competence and clinical judgment are

necessary for the provision of appropriate assessment and treatment services. Behavioral

therapies are the most common treatment approaches for CUD, as these models and interventions

have achieved consistent empirical support (NIDA, 2012). Examples of evidence-based

behavioral approaches include cognitive-behavioral therapy, contingency management

/motivational incentives, the community reinforcement approach, motivational enhancement

therapy/motivational interviewing, and the Matrix Model (see, e.g., Dutra et al., 2008; Lee &

Rawson, 2008; Potenza, Sofuoglu, Carroll, & Rounsaville, 2011; Stotts et al., 2015).

The compulsivity and cravings associated with CUD are two major targets for behavioral

interventions. Cognitive-behavioral therapy (CBT) and contingency management (CM) are the

leading behavioral treatment models for drug addiction (Lee and Rawson, 2008; Stotts et al.,

2015). CM is a reinforcement-based approach that offers concrete rewards for objectively

confirmed abstinence—e.g., earning vouchers for cocaine-negative urine samples (Stotts et al.,

2015). This process involves immediate and delayed gratification, as participants receive an

immediate reward with every clean urine, but only go to the clinic once a week for urine screens.

The value of each reward generally increases over time, so participants are challenged to stay

sober (delay gratification) in anticipation of a future reward. In a systematic review of treatments

for stimulant dependence, Lee & Rawson (2008) found that CM interventions were associated

with significant reductions in cocaine use during the application of the method, but findings from
COCAINE USE DISORDER 15

the post-treatment follow-up revealed inconsistent therapeutic benefits. In Dutra et al.’s (2008)

meta-analysis of behavioral interventions, CM interventions yielded the highest effect sizes,

followed by relapse prevention and other CBT treatments. In the literature, CBT treatments are

consistently associated with reductions in cocaine use (Dutra et al., 2008; Lee & Rawson, 2008;

Potenza et al., 2011). Many CBT modules teach coping strategies to manage cravings, which

work to alter the specific brain circuits implicated in the reinforcement of addictive behaviors

(Potenza et al., 2011).

Current research-based addiction treatment guidelines define self-help groups as

community-level social support that is complementary to professional treatment (NIDA, 2012).

The most prominent self-help groups—e.g., Alcoholics Anonymous (AA); Narcotics

Anonymous (NA); and Cocaine Anonymous (CA)—are based on the 12-step model. There is

evidence that actively integrating 12-step approaches into the formal treatment process enhances

engagement among some stimulant abusers (Donovan & Wells, 2007). Although 12-step

meetings are facilitated by nonprofessionals and have consistently high dropout rates, Donovan

& Wells (2007) point out that 12-step involvement is a low- or no-cost option for individuals

who are seeking mutual support groups.

Research on alternative and complementary addiction treatments suggest the potential

benefits of yoga and mindfulness practices (Khanna & Greeson, 2013; Potenza et al., 2011). In

relation to CBT, studies on mindfulness-based therapies have demonstrated comparable

“efficacy on measures of retention and abstinence and [greater effectiveness] in diminishing

subjective and biological stress responsiveness” (Potenza et al., 2011, p. 7). Potenza and

colleagues note that mindfulness-based therapies may be particularly applicable to women with

CUD because, compared to their male counterparts, they show increased activation in the
COCAINE USE DISORDER 16

cortico-striato-limbic circuit in response to stress cues. Therefore, mindfulness practice may

bolster the recovery process by changing patterns of connectivity in regions of the prefrontal and

anterior cingulate cortices associated with cognitive control and emotional regulation (Potenza et

al., 2011).

No effective pharmacological treatments are currently available for CUD, despite

intensive, ongoing research efforts (Leeman, Robinson, Waters, & Sofuoglu, 2014; Potenza,

Sofuoglu, Carroll, & Rounsaville, 2011; Sofuoglu, 2010). This distinguishes the treatment

options for cocaine dependence from those of alcohol, tobacco, or opioid addiction, as all three

of which have effective and approved medications that can be integrated into a treatment

strategy. However, several pharmacological targets have been identified for the treatment of

CUD. Potenza et al. (2011) reviews recent clinical trials with agonist and antagonist treatments:

Agonist medications are essentially safer, long-acting substitutes for cocaine. Examples of

agonist treatments are nicotine replacement for smoking cessation and methadone for opioid

dependence. Antagonist medications, in contrast, block the rewarding effects of drugs (e.g.,

bubprenorphine for opioid addiction; naltrexone for alcoholism). Immunotherapy vaccines have

been developed as potential antagonist treatments for CUD, but research progress has been

undermined by the initial clinical trials, as the vaccines did not demonstrate significant levels of

efficacy (Potenza et al., 2011). In short-term clinical trials, agonist medications (e.g.,

dextroamphetamine) have reduced drug use in cocaine users. Abuse liability and the long-term

safety of amphetamines in the treatment of CUD are concerns that still need to be addressed

(Potenza et al., 2011).

The complexity of drug use and abuse cannot be distilled into a single explanation,

process, region, or neurotransmitter. Major strides have been made in research on addiction, and
COCAINE USE DISORDER 17

many more will be made in the future. Accordingly, the prevailing approaches to diagnosis,

assessment, treatment of CUD are bound by the strengths and limitations of our present

knowledge. Based on this review of extant literature, it is reasonable to conclude that behavioral

therapies are the most effective treatment for CUD. However, these studies have several

limitations. Firstly, findings have not consistently demonstrated that any of these behavioral

approaches generate long-term therapeutic gains. A second limitation of treatment research is the

tendency for researchers to exclude participants who report polysubstance dependence, co-

occurring psychiatric disorders, or medical conditions associated with chronic stimulant use

(e.g., Stotts et al., 2015). These are typical concomitants of CUD. The consequence of these

exclusion criteria is that a large proportion of research findings are applicable only to a specific

subset of people with CUD. Moreover, experimental research on cocaine addiction is generally

done with rodents or is otherwise limited to the population of treatment-seeking human

participants. This population is a small fraction of the whole. Efforts in research should be

matched or exceeded by social efforts to reduce the stigma associated with drug addiction and

the barriers—real and perceived—that prevent people from receiving treatment that they need.

There is a gap in the literature on post-treatment outcomes of CUD treatment approaches.

There is a need for research that focuses on enhancing the long-term effects of behavioral

treatments (e.g., CBT and CM) and improving the efficacy of behavioral interventions among

cocaine users with more complex presentations. Future research that incorporates other

psychotherapeutic approaches (e.g., multicultural; client-centered; psychoanalytic) may provide

a more nuanced understanding of treatment possibilities. Lastly, more studies on alternative and

complementary treatments (e.g., mindfulness-based approaches; the 12-step model; SMART

recovery) and medications (e.g., N-acetyl-cysteine; see Potenza et al., 2011) are needed in order
COCAINE USE DISORDER 18

to ascertain the therapeutic utility of these treatments in relation to those that already have

substantial empirical support.

COCAINE USE DISORDER 19

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Appendix A

DSM-5 Diagnostic Criteria for Stimulant Use Disorder

A. A pattern of amphetamine-type substance, cocaine, or other stimulant use leading to clinically

significant impairment or distress, as manifested by at least two of the following, occurring

within a 12-month period:

1.   The stimulant is often taken in larger amounts or over a longer period of time than was

intended.

2.   There is a persistent desire or unsuccessful efforts to cut down or control stimulant use

3.   A great deal of time is spent in activities necessary to obtain the substance, use the

substance, or recover from its effects.

4.   Craving, or a strong desire to use the stimulant.

5.   Recurrent stimulant use resulting in failure to fulfill major role obligations at work,

school, home.

6.   Continued stimulant use despite having persistent or recurrent social or interpersonal

problems caused or exacerbated by the effects of the stimulant.

7.   Important social, occupational, or recreational activities are given up or reduced because

of stimulant use.

8.   Recurrent stimulant use in situations in which it is physically hazardous.

9.   Stimulant 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 the

stimulant.

10.  Tolerance, as defined by either of the following:

COCAINE USE DISORDER 26

a.   A need for markedly increased amounts of the stimulant to achieve intoxication or

desired effect.

b.   A markedly diminished effect with continued use of the same amount of the

stimulant.

11.  Withdrawal, as manifested by either of the following:

a.   The characteristic withdrawal syndrome for the stimulant.

b.   The stimulant (or a closely related substance) is taken to relieve or avoid

withdrawal symptoms.
COCAINE USE DISORDER 27

Figures

Figure 1. Brain areas associated with reward and reinforcement (Dubuc, n.d.).

Abbreviations: VTA = ventral tegmental area; MFB = medial forebrain bundle.