Addictions Chapter 11

Acetylcholine

A neurotransmitter. In this chapter it will be referred to by the abbreviation ACH. Nota bene: the adjective form is "cholinergic." There are two types of ACH receptors. The ones that respond to nicotine are known as nicotinic acetylcholine receptors (nACH).

Serotonin

A neurotransmitter. In this chapter, it will be referred to by the abbreviation, 5HT (Shiloh et al., 2006). Nota bene: the adjective form is "serotonergic."

GABA (γ-aminobutyric acid)

A neurotransmitter. In this chapter, it will be referred to by the abbreviation, GABA. Nota bene: the adjective form is "GABAergic."

Glutamate

A neurotransmitter. In this chapter, it will be referred to by the abbreviation, GLU. Nota bene: the adjective form is "glutametergic."

Norepinephrine

A neurotransmitter. In this chapter, it will be referred to by the abbreviation, NA. Nota bene: the adjective form is "noradrenergic."

First-Line Agent

A proven medication typically given first to a patient.

Second-Line Agent

A proven medication typically given to a patient when a first-line agent: (1) does not work, (2) has too many side effects, or (3) stops working.

Alpha 2 Receptor

A receptor located on the NA presynaptic terminal that, when stimulated, inhibits the release of NA

Endogenous

A term meaning "produced by the body."

Neuron

A type of cell that is the basic component of the central nervous system (Julien, 2010). Nota bene: the adjective form is "neuronal."

Cannabinoids

Both (1) the bioactive constituents of the marijuana plant, and (2) endogenous lipids with cannabinoid-like activity (Begg et al., 2005). In this chapter, cannabinoids will be referred to by the abbreviation: CB

Excitotoxicity

Neuronal damage as the result of excessive glutamate exposure

"first messengers.

Neurotransmitters can be thought of as "first messengers." These messengers interact with the postsynaptic nerve to induce consequent intracellular changes (

drugs that impact pupil dilation

When the same amount of this type of medication was applied, Blacks were the least responsive, Asians in the middle, and Caucasians at the other extreme

first messengers set off

Within the postsynaptic nerve, the first messengers set off a cascade of messenger changes including second, third, and fourth messengers. The nature and function of the final three messengers lies beyond the scope of this chapter.

To produce an effect,

a drug must bind to and interact with a receptor (Julien, 2010). Generally, it will do this in one of two ways: as an agonist or antagonist.

Professional counselors differ from prescribing physicians in having

a) more contact with their clients, and (b) more in-depth knowledge on how to form a strong working alliance. Thus, the professional counselor is in a better position to address the knowledge and attitudinal barriers to client-treatment adherence.

ethnic variations in the impact of medications

consideration of the interplay between ethnicity and pharmacotherapy represents best practice for the professional counselor. However, all the reviewers cautioned that intra-ethnic differences in psychopharmacology can be as large as inter-ethnic differences. As such, it is the wise clinician who avoids applying even well-researched ethnic distinctions indiscriminate of the history of each individual client. Hunt and Kreiner (2013) warned that this type of indiscriminate application can be "carte blanche for practicing racialized medicine"

Anticraving Treatment: Second-Line: Lamotrigine (Lamictal)

anticonvulsant class of pharmacotherapies. It works by both blocking voltage-sensitive sodium ion channels and inhibiting the release of excitatory neurotransmitters (e.g., GLU). tend to reduce the reinforcing and rewarding effects of most drugs of abuse, and can also attenuate the reinstatement of drug-seeking behavior. . . . Given that glutamate transmission is one of the primary neurochemical substrates of synaptic plasticity, and the overwhelming evidence reviewed here that all drugs of abuse interact with glutamate transmission, it is not surprising that drugs of abuse can cause long-lasting neuroadaptions of glutamate systems in the brain.

Anticraving Treatment: First-Line: Acamprosate (Campral)

anticraving class of pharmacotherapies. Acamprosate is a GLU antagonist. It modulates overactive GLU brain activity that occurs after stopping chronic heavy alcohol use (Robinson, Meek, & Geniza, 2014). In addition, this medication can lessen the glutametergically driven reinforcing properties of alcohol consumption (Olive, 2005). The purpose of this medication is to maintain abstinence from alcohol (Verheul, Lehert, Geerlings, Koeter, & Brink, 2005). Comprehensive reviews of high-quality studies found that acamprosate effectively maintained complete abstinence in detoxified alcohol-dependent clients. further research on acamprosate is needed.

Anticraving Treatment: Alternative Medications

it is important to note that a variety of alternative medications have been investigated for use with AUD. These medications include kudzu (Tang, Hao, & Leggio, 2012), ayahuasca (Thomas, Lucas, Capler, Tupper, & Martin, 2013), classic hallucinogens (Bogenschutz & Pommy, 2013), and ibogaine.

mental illness treatment preferences of the lay public

less than 15% chose pharmacotherapy as the first treatment option

kinetic profile

every drug will exhibit a unique kinetic profile (like a fingerprint) composed of four processes: Absorption, Distribution, Biotransformation, Elimination

postsynaptic side

facilitates intracellular response

Aversion Treatment, First-Line: Disulfiram (Antabuse)

first pharmacotherapy available for alcohol addiction. Upon use of alcohol, this medication creates a very unpleasant intoxication with the goal of developing an aversion to alcohol

receptor

is a membrane-spanning protein molecule

life of a receptor

is from 12 to 24 hours, after which time it wears out or is reabsorbed into the cell

most important pharmacokinetic concept

is half-life

minute space

is known as the synaptic cleft

presynaptic membrane

is located at the axon terminal of a neuron (i.e., terminal bouton)

Postsynaptic membrane

is located on a dendrite of a neuron.

downregulation and upregulation

refer to the decrease or increase in the total number of receptors

ethnic variations

result from a complex interchange of genetic factors with ethnically based variables such as culture, diet, and societal attitudes

half-life of a drug

is used to determine dosage amounts and time intervals (Preston et al., 2013). Knowledge of a drug's half-life is also important because it tells one how long a drug will remain in the body. For, instance it takes approximately 4 half-lives for 94% of a drug to clear the body

stress-reduction-based craving

the desire for the reduction of tension or arousal. They presented evidence that such a craving is the result of dysregulation of the GABAergic/glutametergic (GABA/GLU) neurotransmitter systems. Specifically, this form of craving arises out of anxiety resulting from a deficiency in the base level of GABA (an inhibitory neurotransmitter) and excess in the base level of GLU (an excitatory neurotransmitter).

reward-sensitivity-based craving

the desire for the rewarding, stimulating, and enhancing effects of alcohol consumption. the result of dysregulation of the opioidergic/dopaminergic (OP/DA) neurotransmitter systems. Specifically, this form of craving arises out of a deficiency in the base levels of endogenous opioids and/or dopamine.

Many view pharmacotherapy

"you can't treat a drug with a drug" (O'Brien, 2005). Others disparage medication as a "crutch" and press clients to remain "drug free"

synapse has three parts:

(1) a minute space between, (2) a presynaptic membrane of one neuron, and (3) a postsynaptic membrane of a receiving neuron

postsynaptic nerve has three parts of note:

(1) ion channels, (2) receptors, and (3) pumps. All three parts can either enhance or suppress the permeability of the postsynaptic membrane

presynaptic axon terminal, there are three parts to note

(1) reuptake transmitter pumps, (2) receptors, and (3) intracellular vesicles containing the neurotransmitter. Please note that there are receptors that can stimulate neurotransmitters and receptors that can inhibit such release.

types of craving for alcohol

(1) reward, (2) relief (stress-reduction), and (3) obsessive (disinhibition)

life cycle of neurotransmitters

(1) synthesis of the transmitter; (2) packaging and storage in synaptic vesicles; (3) if necessary, transport from the site of synthesis to the site of release from the nerve terminal; (4) release in response to an action potential; (5) binding to postsynaptic receptor proteins; and (6) termination of action by diffusion, destruction, or reuptake into cells

individual medications of the same type

(i.e., benzodiazepines) can have very different half-lives.

Promote Medication Compliance

1) ask for—and listen to—the client's beliefs and attitudes about the prescribed medication, (2) work to understand the client's perspective rather than trying to contradict or correct this perspective, (3) understand that it is the client's subjective beliefs, rather than objective medical reality that influences client compliance, (4) withhold responding until the client has discussed all major arguments for and against a medication, and (5) ground any discussion of compliance concerns within the client's point of view.

Dopamine

A neurotransmitter. In this chapter it will be referred to by its common abbreviation, DA. Nota bene: the adjective form is "dopaminergic."

Addiction (from a psychopharmacological perspective)

A chemical or behavior used to produce pleasure and to reduce painful affects, employed in a pattern characterized by two key features: (1) recurrent failure to control the behavior; and (2) continuation of the behavior despite significant harmful consequences (Goodman, 2008). Several neurotransmitters (e.g., glutamate) and hormones (e.g., insulin) are core factors in this desire to produce pleasure and reduce painful affects

Anxiolytics

A class of medication used to treat anxiety

Anticonvulsants

A class of medication used to treat seizures

Downregulation

A decrease in the number of receptors, making the cells less sensitive to a drug

Pharmacodynamics

A drug's impact on the body

Agonist

A ligand (i.e., molecule) that activates a receptor

Antagonist

A ligand that blocks other ligands from activating a receptor

Behavioral Sensitization

A neuroadaptation (resulting from repeated exposure to an addictive drug) that leads to a progressive increase of behavioral responses to that drug (Faria et al., 2008). Put another way, an addictive drug usurps the normal learning mechanisms and thereby "cements" behavioral responses related to drug-seeking behavior; this can progress to a form of habit-based learning so strong that it persists even in the face of tremendous adverse personal consequences (Wolf, 2002).

Chemical Addiction

An addiction to various chemicals such as alcohol

Partial Agonist

An agonist that produces a submaximal response as well as antagonizing full (i.e., system maximal) agonists

Cyclooxygenase (COX)

An enzyme that is part of the inflammatory pathway

Upregulation

An increase in the number of receptors making the cells more sensitive to a drug

drugs as antagonist

Antagonists bind to a receptor but do not activate the receptor (Stolerman, 2010). However, its presence at a receptor blocks the binding of agonists

Opioid

Any agent that binds to opioid receptors. These agents include natural and synthetic narcotics as well as endogenous opioid peptides (National Institute of Drug Abuse, 2000). In this chapter, it will be referred to by the abbreviation, OP. Nota bene: the adjective form is "opioidergic."

Ethical Obligation of pharmacotherapy

As a professional counselor, you are under an ethical obligation to provide your clients treatment based not upon bias but upon scientific evidence of effectiveness. Thus, attention to addiction pharmacotherapy is an ethical mandate no matter what prejudices you encounter at your worksite.

Neurotransmitters

Chemicals released by nerve cells at synapses that influence the activity of other cells. Neurotransmitters may excite, inhibit, or otherwise influence the activity of cells (National Institute of Neurological Disorders and Stroke, 2007). In reference to addiction pharmacotherapy, the main neurotransmitters of interest include acetylcholine (ACH), glutamate (GLU), γ-aminobutyric acid (GABA), serotonin (5HT), norepinephrine (NA), opioid (OP), and dopamine (DA).

Generic Name

Each medicine has an approved name called the generic name (Patient UK, 2006). In this chapter, the generic name will be used first, followed by the most common brand names in parentheses.

Hormones

Extracellular signaling molecules secreted by specialized cells that are released into the blood to exert specific biochemical actions on target cells located at distant sites

multiple types

In addiction, there is not one type of craving, but multiple types. These types are psychological readouts of dysregulation in different neurotransmitter systems

Ion Channels

Ion channels are membrane proteins that form a pore to allow the passage of specific ions. The opening and closing of ion channels are controlled by various means, including voltage

Axon

Long nerve cell fibers that conduct electrical impulses. Axons contact other nerve, muscle, and gland cells at synapses and release neurotransmitters that influence those cells

Brand Name

Medicines may have one or more brand names. These names are chosen by the company that makes them. Several companies may make the same medicine, each with its own brand name (Patient UK, 2006). In this chapter, the generic name will be used first, followed in parentheses by the most common brand names.

Monotherapy and Polytherapy

Monotherapy is the use of one medication in treatment. Polytherapy is the use of multiple medications in treatm

drugs as agonists

Once it binds to a receptor, an agonist activates or enhances cellular activity in a similar way to endogenous transmitters (Shiloh, Nutt, & Weizman, 2001). This activity sets off the complex cascade of intracellular messengers mentioned earlier.

N Methyl D Aspartate (NMDA)

One type of glutamate receptor. Antagonists to this type of receptor include the drugs of abuse ketamine and phencyclidine (PCP).

Reuptake

Reabsorption of a neurotransmitter by way of a reuptake transporter pump embedded in a cell membrane

Alcohol Withdrawal and Anticraving Treatment: Second-Line: Sodium Oxybate-SMO (Xyrem)

SMO interacts in a complex manner with both GABA and γ-hydroxybutyric acid (GBH) receptors. This complexity leads to SMO having multiple beneficial effects. First, it has sedative and anxiolytic effects similar to benzodiazepines and thus can treat alcohol withdrawal symptoms. Second, it has an alcohol-mimicking effect that lowers craving for that substance and hence decreases the likelihood of relapse. The benefit to using SMO is that its side-effects profile is lower than the first line medications for both alcohol withdrawal and relapse prevention.

Alcohol Withdrawal Syndrome

Symptoms of alcohol withdrawal result from the lack of opposition to sympathetic nervous system activity in the brain once the central nervous system (CNS) depressant (alcohol) is stopped. Symptoms of uncomplicated withdrawal include tremor, tachycardia, increased blood pressure, increased body temperature, diaphoresis, insomnia, anxiety, and gastrointestinal upset. . . . Ten percent of alcoholics experience severe symptoms such as seizures and delirium tremens. In delirium tremens, or alcohol withdrawal delirium, the patient suffers from confusion, disorientation, illusions, and visual, tactile, and auditory hallucinations.

practice guideline for alcohol withdrawal

The American Society of Addiction Medicine's (2003) practice guideline for alcohol withdrawal suggests the use of longer half-life (hl) benzodiazepines such as lorazepam (Ativan, 12-hour hl), diazepam (Valium, 20-hour hl), and chlordiazepoxide (Librium, 30-hour hl).

Agonist Substitution Pharmacotherapy

The administration of a medication pharmacologically related to the one producing dependence. Agents suitable for this pharmacotherapy are those that have the capacity to prevent the emergence of withdrawal symptoms and reduce craving. In general, it is desirable for substitution medicines to have a longer duration of action than the drug they are replacing, so as to delay the emergence of withdrawal symptoms and reduce the frequency of administration. This results in less disruption of normal life activities by the need to obtain the abused substance. Equivalent terms: substitution therapy, agonist pharmacotherapy, agonist replacement therapy, substitution maintenance therapy, and agonist-assisted therapy (

Pharmacokinetics

The body's impact upon a drug

Receptor

The location at which ligands bind to the nervous system to exert their effects (i.e., chemical signaling between and within cells)

Sensitization

The repeated exposure to psychostimulants that results in increased behavioral responses to the same dose of drug (Torres-Reverón & Dow-Edwards, 2005). Cross-sensitization to other drugs is possible.

Ethnic Psychopharmacology

The study of differences in drug response and disposition among ethnic groups

Half-Life

The time for the plasma level of a drug to fall by 50% (Julien, 2010). In this chapter, it will be referred to by the abbreviation "hl."

Dendrites

The treelike branches from nerve cell bodies that receive signals from other nerve cells at synapses

Immunotherapy

The use of drug antibodies to prevent drugs of abuse from entering the central nervous system. How does immunotherapy work? The leading expert in addiction immunotherapy describes this therapy as follows: "Drugs of abuse are small molecules that can readily cross the blood brain barrier, while antibodies are larger molecules that cannot get into the brain" (Kosten, 2005, p. 177). Thus, he notes that any drug bound to an antibody also cannot cross the blood-brain barrier and cannot enter the brain. The primary uses in addiction treatment are (1) overdose treatment and (2) relapse prevention

play a role in the neurochemical basis of alcohol dependence

The γ-aminobutyric acid (GABA), glutametergic (GLU), opioidergic (OP), dopaminergic (DA), cholinergic (ACH), and serotonergic (5HT) systems

Cross-ethnic variation

There are considerable cross-ethnic variations in drug effects

psychological interventions

aimed at pharmacotherapy adherence improve addiction treatment outcomes

Anticraving Treatment: First-Line: Naltrexone (ReVia, Depade)

anticraving class of pharmacotherapies. Garbutt (2009) describes it as follows: Naltrexone, by blocking endogenous opioids, reduces the rewarding properties of alcohol . . . thereby counteracting this important component of the behavioral response to alcohol. In fact, in the initial human studies of naltrexone for alcohol dependence, it was reported that patients who consumed alcohol and who were taking naltrexone were significantly less likely to experience their usual "high" or level of intoxication. . . . In addition, naltrexone has been reported to reduce alcohol craving in a number of clinical trials. excellent evidence of naltrexone's efficacy with alcohol dependence

First-Line: Diazepam (Valium) and the Other Longer Half-Life Benzodiazepines

anxiolytic class of pharmacotherapies. There is a long-standing history on the use of benzodiazepines to alleviate alcohol withdrawal. A Cochrane Library review on such use of benzodiazepines reported this type of medication effective against alcohol withdrawal symptoms when compared to placebo. While effective, benzodiazepines increase sedation, memory deficits, respiratory depression, and addiction

disulfiram efficacy

are mixed (Kiefer & Mann, 2010). The effectiveness of this medicine seems to be limited to three client groups: (1) adherent clients, (2) specific high-risk clients, and (3) clients with whom administration can be supervised

disinhibition-based craving

as the desire emerging from a lack of control. This lack can be either cognitive/attentional (i.e., obsessive) or behavioral, or both. They presented evidence that such a craving is the result of dysregulation of the 5HT neurotransmitter system. Specifically, this craving arises out of a deficiency in the base level of 5HT. The obsessive disinhibition form of craving can be defined as a loss of control in which obsessions flood in and overwhelm perception (Addolorato, Abenavoli, Leggio, & Gasbarrini, 2005). This craving is similar to obsessive-compulsive disorder except that the obsession centers on alcohol (Anton, 2000). The behavioral disinhibition form of craving can be defined as a loss of control over impulsiveness, harm avoidance, and deviant behavior

Second-Line: Baclofen (Lioresal)

belongs to the anticonvulsant class of pharmacotherapies. Baclofen is a GABA agonist. Baclofen monotherapy was able to suppress alcohol withdrawal symptoms (Leggio, 2009). In addition, baclofen lowered alcohol intake and alcohol craving

Second-Line: Carbamazepine (Tegretol)

belongs to the anticonvulsant class of pharmacotherapies. It works by both blocking voltage-sensitive sodium ion channels and inhibiting GLU release (Stahl, 2013). It has some advantages over the traditional use of benzodiazepine for alcohol withdrawal, including lack of (a) addictive potential, (b) interaction with alcohol, (c) a greater than benzodiazepine side effect profile, and (d) sedatory effect

number of medications for alcohols

in the last 50 years more than 150 medications have been used to treat various aspects of alcohol dependence

presynaptic side

of this neurology controls neurotransmitter release. Generally, most neurons release only one transmitter

craving

plays a crucial role in (1) the transition from substance use to dependence, (2) the mechanisms underlying relapse, and (3) treatment

sex influences

sex influences the behaviors induced by drugs, as well as pharmacological responses to drugs. Further research examining the factors that underlie sex differences may allow for the development of safe and effective sex-specific behavioral and pharmacological therapies for drug abuse.

Prominent reasons for psychiatric medication noncompliance

sexual dysfunction (Kennedy et al., 2006), weight gain (Kalinichev et al., 2005), and medication interfering with personal strategies for treatment

intensified culture and ethnicity

the importance of culture and ethnicity has been significantly intensified because of the rapid and accelerating population shifts occurring in all metropolitan areas of the world. Furthermore, because of the rapid pace of intercontinental transportation and large-scale migration, most psychiatrists no longer have the luxury of practicing their trades in culturally or ethnically homogeneous settings. Patients seeking help enter the clinic with divergent beliefs, expectations, dietary practices, and genetic constitution. These all have the potential of significantly affecting the outcome of psychopharmacotherapy and should not be ignored.

enzyme (CYP 2D6)

the presence of an enzyme (CYP 2D6) that strongly impacts drug metabolism (n.b., PM = Poor Metabolizer).

endogenous chemicals that serve as neurotransmitters.

the three with most relevance to addiction pharmacotherapy are serotonin (5HT), dopamine (DA), and norepinephrine (NA).

clinicians who held a 12-step treatment philosophy

were significantly less likely to support a pharmacotherapy intervention even when they had been provided evidence as to pharmacotherapy's effectiveness

polymorphisms (DNA variations)

within the following lead to deregulation in alcohol craving: (a) appetite-stimulating hormones such as ghrelin, (b) appetite-suppressing hormones such as leptin, and (c) volume-regulating hormones such as vasopressin. The team hopes to identify how these hormone polymorphisms can be modified in order to limit their effect on alcohol craving.