Presented By : Dr. Karrar Husain

Moderator : Dr. M. Amir Usmani

CONTENTS

1. Introduction

2. Brief history and epidemiology

3. Biology

4. Learning and conditioning

5. Psychodynamic theory

6. Environmental and other factors

1. DSM and ICD

2. Terminology

In DSM 5 substance related disorder are classified in substance relatedand addictive disorder.

Substance related disorder substance use disorder and substanceinduced disorder.

Substance use disorder in DSM-5 combines the DSM-IV categories ofsubstance abuse and substance dependence into a single disordermeasured on a continuum from mild to severe k/a substance usedisorder. (only 2 are required).

Substance induced disorder consist of withdrawal, intoxication, andother substance induced mental disorder.

DSM 5

Substance-Use Disorder A. A maladaptive pattern of substance use leading to clinically significant

impairment or distress, as manifested by 2 (or more) of the following,occurring within a 12-month period:

1. recurrent substance use resulting in a failure to fulfill major role obligationsat work, school, or home (e.g., repeated absences or poor work performancerelated to substance use; substance-related absences, suspensions, orexpulsions from school; neglect of children or household)

2. recurrent substance use in situations in which it is physically hazardous(e.g., driving an automobile or operating a machine when impaired bysubstance use)

3. continued substance use despite having persistent or recurrent social orinterpersonal problems caused or exacerbated by the effects of the substance(e.g., arguments with spouse about consequences of intoxication, physicalfights)

4. tolerance, as defined by either of the following:

a. a need for markedly increased amounts of the substance to achieveintoxication or desired effect

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

5. withdrawal, as manifested by either of the following:

a. the characteristic withdrawal syndrome for the substance

b. the same substance is taken to relieve or avoid withdrawal symptoms

6. the substance is often taken in larger amounts or over a longerperiod than was intended.

7. there is a persistent desire or unsuccessful efforts to cut down orcontrol substance use

8. a great deal of time is spent in activities necessary to obtain thesubstance, use the substance, or recover from its effects

9. important social, occupational, or recreational activities are given upor reduced because of substance use

10. the substance use is continued despite knowledge of having apersistent or recurrent physical or psychological problem that is likelyto have been caused or exacerbated by the substance

11. Craving or a strong desire or urge to use a specific substance.

Severity specifiers:

Mild : 2-3 criteria

Moderate : 4 or 5

Severe : 6 or more

ICD 10

F10 - F19 MENTAL AND BEHAVIOURAL DISORDERS DUE TO PSYCHOACTIVE SUBSTANCE USE

F10.- DISORDERS DUE TO USE OF ALCOHOL

F11.- DISORDERS DUE TO USE OF OPIOIDS

F12.- DISORDERS DUE TO USE OF CANNABINOIDS

F13.- DISORDERS DUE TO USE OF SEDATIVES OR HYPNOTICS

F14.- DISORDERS DUE TO USE OF COCAINE

F15.- DISORDERS DUE TO USE OF OTHER STIMULANTS, INCLUDING CAFFEINE

F16.- DISORDERS DUE TO USE OF HALLUCINOGENS

F17.- DISORDERS DUE TO USE OF TOBACCO

F18.- DISORDERS DUE TO USE OF VOLATILE SOLVENTS

F19.- DISORDERS DUE TO MULTIPLE DRUG USE AND USE OF OTHER PSYCHOACTIVE SUBSTANCES

Dependence - The repeated use of a drug or chemical substance, withor without physical dependence. Physical dependence indicates analtered physiologic state caused by repeated administration of a drug,the cessation of which results in a specific syndrome.

Abuse - Use of any drug, usually by self-administration, in a mannerthat deviates from approved social or medical patterns.

Misuse - Similar to abuse, but usually applies to drugs prescribed byphysicians that are not used properly.

Addiction - The repeated and increased use of a substance, thedeprivation of which gives rise to symptoms of distress and anirresistible urge to use the agent again and which leads also to physicaland mental deterioration.

Intoxication - A reversible Syndrome caused by a specific substancethat affects one or more of the following mental functions: memory,orientation, mood, judgment, and behavioral, social, or occupationalfunctioning.

CTP 9th edition.

Cross-tolerance - Refers to the ability of one drug to be substituted foranother, each usually producing the same physiologic andpsychological effect (e.g., diazepam and barbiturates). Also known ascross-dependence.

Codependence - Term used to refer to family members affected by orinfluencing the behavior of the substance abuser. Related to the termenabler, which is a person who facilitates the abuser’s addictivebehavior. Enabling also includes the unwillingness of a family memberto accept addiction as a medical-psychiatric disorder or to deny thatperson is abusing a substance.

CTP 9th edition.

HISTORY Opium has been used for medicinal purposes for at least 3,500 years.

References to cannabis (marijuana) as a medicine can be found inancient chinese herbals.

Wine is mentioned frequently in the bible.

Indigenous people of the western hemisphere were smoking tobaccoand chewing coca leaves generations before the arrival of the spaniards.

In asia, opium smoking was a major problem in the 18th and 19thcenturies, new problems related to opium were seen there and in otherparts of the world after morphine, its most active alkaloid, was isolatedin 1806.

Intravenous (IV) morphine and heroin use began to spread in the earlypart of the 20th century.

Although tobacco use was common by the 19th century, the seriousadverse medical consequences associated with it did not emerge untilthe 20th century, when new methods of curing the leaves produced amild smoking tobacco, and cigarettes were introduced

Medicalizing Excessive Drug Use In 1810, Benjamin Rush, suggested that excessive use of alcohol was a

disease.

in 1835, Samuel Woodward, a pioneer in the establishment of asylumsfor the insane, advocated similar asylums for inebriates.

In 1870, estb. Of The American Association for the Cure of Inebriates(AACI), dedicated to setting up hospitals for such people, conductingresearch, and teaching medical students and physicians how to treatinebriety.

Thomas Crothers, the secretary of AACI, saw inebriate asylums asplaces to treat all those who used any variety of intoxicant or narcotic toexcess

CTP 9th edition.

Burden of problem According to WHO there are 2 billion alcohol users, 1.3 billion smokers

and 185 million drug users.

http://www.who.int/substance_abuse/facts/global_burden/en/

There is no National epidemiological data collection system for Alcoholand Drugs in INDIA.

Prevalence estimates for alcohol use disorders (12-month prevalence,%)

Female (15+ years) - Year 2004 -0.42

Male (15+ years) - Year 2004 -3.47

Prevalence estimates for drug use disorders (12-month prevalence, %)

Female (15+ years) - Year 2004- 0.03

Male (15+ years) - Year 2004 - 0.24

World Health Organization 2010

Global Burden of Disease (GBD) estimate, 2004.

Risk factors Men > women, 2:1

Adults who did not complete high school are more likely than collegegraduates to have become dependent on illegal drugs.

Unemployed : employed.. 2: 1

Younger age of onset.

Individuals with a serious mental illness are more than twice as likelyto have used an illegal drug and to have been cigarette smokers.

CTP 9th ed

1- ACUTE EFFECT OF DRUGS ( REWARD CIRCUITS)

2-MECHANISM OF ACTION OF VARIOUS DRUGS

3- CHRONIC EFFECTS OF DRUG

4- VULNERABILITY AND GENETICS

Substance abuse and addiction are complex phenomena that defysimple explanation or description.

A tangled interaction of factors contributes to an individual’s seekingout, using, and perhaps subsequently abusing drugs.

Since more individuals experiment with drugs than eventually developsubstance abuse problems, great interest persists in understandingwhat differentiates these groups.

Factors that can play a role in drug abuse susceptibility include aperson psychological makeup, biological response to drugs andenvironmental situation, and the availability of drugs.

Two biological factors contribute to substance abuse and addiction:

1. The effects drugs of abuse exert on the individual.

2. The biological status of the individual taking drugs .

DRUG ACTIONAcute Actions

What separates drugs of abuse from other psychoactive drugs ?

• One of the most striking features of drug addiction is how few chemicals are subject to abuse.

• All known congeners of all known chemicals, approximately 30,000,000 chemical substances [Gardner, 2005]. Yet, only approx 100 are addictive.

• What makes these 100 chemicals addictive, while the remaining 30,000,000 chemicals lack this property?

All addictive drugs are subjectively rewarding, reinforcing and pleasurable.

All addictive drugs (excep) activate reward circuitry of brain -producingsubjective ‘high’ that drug abuser seeks.

Degree of such activation of the brain’s reward circuitry correlates wellwith the degree of subjective high.

REWARD CIRCUITS

Stahl’s essential psychopharmacology.

The mesolimbic dopamine circuit

The final common pathway of reinforcement and reward.

Also k/a “pleasure center” of the brain and dopamine to be the“pleasure neurotransmitter.

Natural ways to trigger your mesolimbic dopamine neurons to releasedopamine, ranging from intellectual accomplishments, to athleticaccomplishments, to enjoying a good symphony, to experiencing anorgasm. These are called as “natural highs”.

The inputs to the mesolimbic pathway that mediate these natural highsinclude a naturally occurring substances - endorphins, anandamide,acetylcholine, and dopamine itself.

Drugs of abuse also have a final common pathway of causing themesolimbic pathway to release dopamine, more explosive andpleasurable than that which occurs naturally.

A drug-induced reward causes such wonderful feeding of dopamine topostsynaptic limbic dopamine receptors that they furiously crave evenmore drug to replenish dopamine once the drug stops working, leadingone to be preoccupied with finding drug and thus beginning a viciouscycle of abuse, addiction, dependence, and withdrawal

0

50

100

150

200

0 60 120 180

Time (min)

% o

f B

as

al D

A O

utp

ut

NAc shell

Empty

Box Feeding

Source: Di Chiara et al.

FOOD

100

150

200

DA

Co

nc

en

tra

tio

n (

% B

as

eli

ne

)

MountsIntromissionsEjaculations

15

0

5

10

Co

pu

latio

n F

req

uen

cy

SampleNumber

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

ScrScr

BasFemale 1 Present

ScrFemale 2 Present

Scr

Source: Fiorino and Phillips

SEX

Natural Rewards Elevate Dopamine

Levels

0

100

200

300

400

500

600

700

800

900

1000

1100

0 1 2 3 4 5 hr

Time After Amphetamine

% o

f B

as

al R

ele

as

e

DADOPACHVA

Accumbens AMPHETAMINE

0

100

200

300

400

0 1 2 3 4 5 hrTime After Cocaine

% o

f B

as

al R

ele

as

e

DADOPACHVA

AccumbensCOCAINE

0

100

150

200

250

0 1 2 3 hr

Time After Nicotine

% o

f B

as

al R

ele

as

e

AccumbensCaudate

NICOTINE

Source: Di Chiara and Imperato

Effects of Drugs on Dopamine Release

100

150

200

250

0 1 2 3 4hrTime After Ethanol

% o

f B

as

al R

ele

as

e0.250.512.5

Accumbens

0

Dose (g/kg ip)

ETHANOL

Much greaterActivity than anyOther drug of abuse.

The reactive reward system Addicts act impulsively, automatically, and obligatorily to cues that

lead them to seek and ingest more drug..mediated by reactive rewardsystem.

Upon repeated exposure to drugs of abuse, this reactive reward systempathologically “learns” to trigger drug seeking behavior and“remembers” how to do this when confronted with internal cues suchas craving and withdrawal and external cues from the environmentsuch as people, places, and paraphernalia associated with past druguse.

Connections of VTA DA neurons with the amygdala are involved withreward learning.

Once reward learning has been conditioned in the amygdala,connections of the amygdala back to the VTA DA neuron latercommunicate whether anything relevant to the previously rewardingdrug abuse experience is being detected.

Connections of the amygdala with the nucleus accumbens tell thespiny neurons there that emotional memories have been triggered byinternal or external cues, and instruct these spiny neurons to takeaction impulsively, right away, automatically, obligatorily, and withoutthought, almost as a reflex action, to find and take more drugs.

The reflective reward system Includes important connections from prefrontal cortex down to the

nucleus. These connections are the first legs of cortico-striatal-thalamic-cortical (CSTC) loops.

1. Prefrontal projections from the orbitofrontal cortex may be involvedin regulating impulses,

2. Dorsolateral prefrontal cortex (DLPFC) analyzing the situation,and regulating whether it is rational to take an action.

3. Ventromedial prefrontal cortex may try to integrat impulsivenessfrom OFC with analysis and cognitive flexibility from DLPFC with itsown regulation of emotions, and come up with a final decision ofwhat to do.

The reflective reward system is also involved in the will power to resistdrugs.

When fully developed and functioning properly ..it provide motivationfor pursuing more naturally rewarding experiences such as education,accomplishments, recognition, financial benefits, career development,enriching social and family connections, etc

Turning reward into goal-directed behavior: output of the reward system

The output of the reward system is really just the completion of CSTCloops starting in the prefrontal cortex.

Nucleus Accumbens via GABA-ergic neurons to the ventral pallidum via GABA-ergic neurons to the thalamus, and then project back upto the prefrontal cortex, where behaviors are implemented, such aslearning and activities resulting in long-term rewards or drug-seekingbehavior resulting in short-term rewards.

First time you take a drug, there is immediate pharmacological actionupon the mesolimbic pleasure center……Dopamine is released, pleasure isexperienced and the amygdala “learns” that this is a rewarding experience.Reward has now been conditioned in the amygdala.

• when cues are encountered, the amygdala signals dopamine neurons in the ventral tegmentalarea (VTA) that something good is coming ,This leads to dopamine release in the nucleusaccumbens which triggers GABA-ergic input to the thalamus, thalamic input to the prefrontalcortex, and leads to action such as drug-seeking behavior

But can impulses from the reactive reward system ever beresisted?

What is the role of will power over temptation?

when temptation occurs with the opportunity to ingest drugs arising ata party, in a bar, or when seeing or feeling drugs or their paraphernalia,the amygdala anticipates the pleasure that the drugs would bring in bysignaling an impulsive choice to the VTA that urges output from thenucleus accumbens to engage in behavior that leads to ingesting thedrugs again.

The OFC in prefrontal cortex is signaling craving and voting for moredrug ingestion as well.

When drug anticipation occurs, this signals an impulsive choice to theventral tegmental area (VTA) to release dopamine in the nucleusaccumbens, which in turn produces output to engage in behavior that leadsto ingesting drugs again.

Will power can be represented in the reward system as the ability ofprefrontal circuits to become activated and prevent impulses beingexpressed as drug-seeking behavior.

For example, Reflective reward system allows the time to evaluatewhether losing your driver’s license, getting into an auto accident,losing your job or your relationship is worth becoming intoxicated, andif the answer is no, can trigger the choice not ingesting the drug.

The dorsolateral prefrontal cortex (DLPFC) interprets the various signals and, showing cognitive flexibility, decides whether to take the action of drug ingestion (5). (B) If the reflective reward system (prefrontal circuits) is activated, this can prevent impulses (temptation) from being expressed as behavior.

MECHANISM OF ACTION OF VARIOUS DRUGS

Nicotine1. Nicotine directly causes dopamine release in the nucleus accumbens

by binding to alpha 4 beta 2 nicotinic postsynaptic receptors ondopamine neurons in the ventral tegmental area (VTA).

2. Nicotine binds to alpha 7 nicotinic presynaptic receptors onglutamate neurons in the VTA, which in turn leads to dopaminerelease in the nucleus accumbens.

3. Nicotine also seems to desensitize alpha 4 beta 2 postsynapticreceptors on GABA interneurons in the VTA; the reduction of GABAneurotransmission disinhibits mesolimbic dopamine neurons andthus is a third mechanism for enhancing dopamine release in thenucleus accumbens.

Alcohol The pharmacology of alcohol is poorly understood and its mechanism

of action is thought to be somewhat nonspecific.

Alcohol can have effects on a wide variety of neurotransmitter systems.

Enhancing inhibitory neurotransmission at GABA synapses andreducing excitatory neurotransmission at glutamate synapses

depress CNS neuronal functioning intoxicating, amnestic, andataxic effects.

Alcohol either act directly mu opiate receptors or indirectly act byreleasing endogenous opiates such as enkephalin…actions on opiatesynapses is thought to be the release of DA in the nucleus accumbens.

Alcohol may also have some actions on cannabinoid receptors.

Opiates Act as agonists at mu, delta, and kappa opiate receptors, particularly at

mu sites.

Opiates act as neurotransmitters released from neurons that arise inthe arcuate nucleus and project both to the VTA and to the nucleusaccumbens and release enkephalin.

The opiates induce euphoria, which is their main reinforcing property.

Stimulants The main mechanism of action of cocaine is to block reuptake and

cause the release of monoamines, principally dopamine (DA) but alsonorepinephrine (NE) and serotonin (5HT).

Amphetamine as an inhibitor of the dopamine transporter (DAT) andalso of the vesicular monoamine transporter (VMAT).

The potential abuse properties of stimulants stem from their ability toenhance dopamine release in the nucleus accumbens.

Marijuana delivers its active ingredients, the cannabinoids (e.g., THC;delta-9-tetrahydrocannabinol), which interact with the brain’s owncannabinoid receptors to trigger dopamine release in the nucleusaccumbens.

Sedative/ hypnotics are positive allosteric modulators (PAMs) forGABA-A receptors.

Inhalants : Agents such as toluene are thought to be direct releasers ofdopamine in the nucleus accumbens.

Phencyclidine and ketamine : act as antagonists of NMDA receptors,actions at glutamate synapses within the reward system.

Hallucinogens : The hallucinogens are a group of agents that act atserotonin synapses in the reward system.

Addictive drugs of different classes act on this brain reward neuralcircuit at different points to activate the circuit and produce drug-induced high.

Barbiturates, benzodiazepines, cannabinoids, ethanol, nicotine andopiates act on synapses in ventral tegmental area.

Amphetamines, cannabinoids, cocaine, opiates and dissociativeanesthetics eg. ketamine and phencyclidine act on synapses in nucleusaccumbens

Addictive drugs effectively ‘hijack’ brain’s reward circuits, activatingthem more strongly than natural rewards, and diverting the drugaddict’s life to pursuit of drug- induced pleasure at the expense of‘getting off ’ on life’s normal pleasures and rewards….to begin withanyway!

CHRONIC EFFECTS OF DRUG

NEUROADAPTATIONS IN SUBSTANCE DEPENDENCE

Chronic drug and alcohol use produces numerous neurobiologicalchanges in several brain regions.

These changes occur at virtually every level of information processing,ranging from neurotransmitters and receptors to intracellular signalingpathways and regulation of gene expression to long-term structuralchanges that alter synaptic plasticity.

These changes ultimately could alter entire neural networks withimpact on motivation, emotion, decision making, and other cognitiveprocesses.

From: Nestler - Transcriptional and Epigenetic Mechanisms of Addictionhttp://az9194.vo.msecnd.net/pdfs/100401/EB10L5.pdf

From: Nestler - Transcriptional and Epigenetic Mechanisms of Addictionhttp://az9194.vo.msecnd.net/pdfs/100401/EB10L5.pdf

From: Nestler - Transcriptional and Epigenetic Mechanisms of Addictionhttp://az9194.vo.msecnd.net/pdfs/100401/EB10L5.pdf

VULNERABILITY AND GENETICS

why does one person become dependent on drugs while another,exposed to the same environment and experiences, does not?

There is likely to be a genetic component to substance abuse andaddiction.

That is, inherited differences among individuals affect their response todrugs.

The children of alcoholic parents are at higher risk for developingalcoholism and drug dependence than are children of nonalcoholicparents.

The higher risk for alcoholism manifests itself even when children areadopted by nonalcoholic families soon after birth. Dependence onother drugs also shows a familial pattern.

Numerous studies of laboratory animals have revealed geneticallytransmitted differences in the reinforcing effects of alcohol and variousdrugs, such as cocaine and opioids, and show that genetic factorspowerfully influence sensitivity to toxic effects.

Studies of boys adopted soon after birth have shown higher rates ofalcoholism among those whose biological fathers were alcoholics thanamong those whose biological fathers were not.

Some adoption studies point toward subtypes of alcoholism amongmen: One is a later-onset disorder that is less severe and far moresensitive to environmental factors (type I OR low risk), and the other isassociated with early-onset, antisocial behavior and criminality in thebiological fathers and a stronger genetic basis for the increasedvulnerability (type II OR high risk).

High risk and low risk children and adolescents HR children have :

smaller (slower maturing) brain areas - Frontal BRAKES- ANT CING

Less mature connecting WHITE matter tracts - reduced white matter being associated with greater impulsivity.

ALTERED EMOTIONAL REACTIVITY AND REACTION TO SOCIAL CUES. Deficits in recognizing anger and fear recognition difficulties in recognizing and responding appropriately to others emotions and thoughts------ >> More asocial and drinking helps them to become more prosocial which is highly rewarding.

Hypo-activation in high risk subjects for Recognition of Angry &Fearful faces inability to recognize these emotions may lead toincreased risk taking behavior.

HR respond differently to alcohol Greater CNS “stimulation”….greaterreinforcing effect of alcohol; BUT……HR receive less warning ofintoxication.

HR young adults receive increased CNS reinforcement from alcohol…but lower negative signals of intoxication frequent drug use andbingeing.

P300 A P300 event-related potential (ERP) is a brief electrical wave in the

EEG, reflects active stimulus processing that is affected by attentionand memory and is genetically mediated

Measure of the way the brain pays attention and discriminatesbetween potentially important and non-important stimuli.

Marker of CNS hyperexcitability - lower amplitude of P300 associatedwith generalized disinhibition, associated with the early onset of anumber of deviant behaviors

Several studies: HR children have demonstrated reduced P300amplitude

Differences not always replicable in adults (Gandhi & Benegal, 2004)

Benegal V, Jain S, Subbakrishna DK, Channabasavanna SM. Psychiatr Genet. 1995;5(4):49-56.

Iacono and McGue, 2006; Porjesz and Rangaswamy, 2007

‘Reward Deficiency’ as a Driving Force in Addiction

In 1996, Blum et al. proposed that many aspects of addiction are drivenby a chronic basal deficiency in brain reward.

The fundamental notion : that drug addicts are either born with oracquire a deficiency state in the dopaminergic brain substrates ofreward and turn to addictive drug use to remedy this reward deficiency.

‘IF this be so, then our goals are really two- fold: first, to rescue addictsfrom the clutches of their addictions, and second, to restore theirreward systems to a level of functionality that will enable them tofunction appropriately.

Gardner (2011) In, Clark MR, Treisman GJ (eds): Chronic Pain and Addiction. Adv Psychosom Med. Basel, Karger, 2011, vol 30, pp 22–60

Genetics Heritability estimates for nicotine, alcohol, and drug addiction are in

the range of 50% to 60%.

In general, it appears that environmental factors have a stronger effecton initiation, whereas genetic factors play a larger role in the transitionfrom regular use to the development of addiction.

(Heath et al., 1997;Tsuang et al., 1998;Kendler et al., 2003;Li, 2006)

(Vink et al., 2005).

The Genetic Basis of Addiction, Chad Epps and Elizabeth Laura Wright

Genetics of Alcohol Dependence

Polymorphisms in the alcohol metabolizing enzymes are the most stronglyassociated genetic variants that influence alcohol consumption andalcohol dependence.

Protective role for the deficiency of ALDH2 in alcohol dependence

Several known genetic variants cause amino acid changes in these proteinsand alter enzymatic activity.

ADH1B*2, or rs1229984, diminishes ADH1b enzymatic activity several fold,and ALDH2*2, or rs671, results in a nearly inactive enzyme (Edenberg,2007). These genetic variants reduce the probability of heavy alcoholconsumption and the development of alcohol dependence.

The mechanism by which variants of these enzymes influence the riskof developing alcohol dependence is hypothesized to be through anelevation of acetaldehyde levels after drinking, leading to facialflushing, nausea, and other adverse reactions.

(Enoch, 2008

Genetic influences for other Drug Addictions

Endogeneous opioid system clearly plays a role in addiction, and anamino acid change in the μ opioid receptor (OPRM1) displaysfunctional changes with up to threefold variation in the affinity of thereceptor to bind beta-endorphin.

However, a large scale meta-analysis does not demonstrate that thisvariant alters the risk of developing addiction.

(Bond et al., 1998).

(Arias et al., 2006).

Studies of Nicotine Dependence

The most robust genetic finding that alters the risk of developing heavysmoking is in the chromosome 15q25 region, which contains the α5, α3,and β4 nicotinic receptor subunit gene cluster (CHRNA5, CHRNA3,CHRNB4).

Variation in an independent group of nicotinic receptors is alsoassociated with the development of heavy smoking and nicotinedependence. The nicotinic receptor gene cluster on chromosome 8 thatincludes the α6 and β3 nicotinic receptor subunit gene cluster(CHRNA6, CHRNB3) is correlated with smoking behavior.

The importance of nicotine metabolism and variation in the CYP2a6region on chromosome 19 was recently reinforced by the GWAS meta-analysis studies in which variants in this region were associated withnumber of cigarettes smoked per day.

(Thorgeirsson et al., 2010; Tobacco and Genetics Consortium, 2010).

The chromosome 15 variant in the α5 nicotinic receptor, whichinfluences the development of nicotine dependence, has also beenindependently shown to contribute to the occurrence of alcohol andcocaine dependence.

The minor allele is correlated with an increased risk for nicotinedependence is associated with a decreased risk for alcohol and cocainedependence.

(Grucza et al., 2008; Chen et al., 2009; Sherva et al., 2010)

Drug use, whether occasional or compulsive, can be viewed as behaviormaintained by its consequences.

Any event that strengthens an antecedent behavior pattern can beconsidered a reinforcer of that behavior. In that sense, certain drugsreinforce drug-taking behavior.

Drugs can also reinforce antecedent behaviors by terminating somenoxious or aversive state such as pain, anxiety, or depression.

In some social situations, the use of the drug can be reinforcing if itresults in special status or the approval of friends.

Each use of the drug evokes rapid positive reinforcement, either as aresult of the rush (the drug-induced euphoria), alleviation of disturbedaffects, alleviation of withdrawal symptoms, or any combination ofthese effects.

The paraphernalia (needles, bottles, cigarette packs) and behaviorsassociated with substance use can become secondary reinforcers, aswell as cues signaling availability of the substance, and in theirpresence, craving or a desire to experience the effects increases.

With socially acceptable substances, such as tobacco, use becomes sowoven into the matrix of daily functioning that some users arereminded of the substances when performing ordinary tasks.

Classical Conditioning Opioid and alcohol withdrawal phenomena can be conditioned to

environmental or interoceptive stimuli.

For a long time after withdrawal (from opioids, nicotine, or alcohol),the addict exposed to environmental stimuli previously linked withsubstance use or withdrawal may experience conditioned withdrawal,conditioned craving, or both.

The most intense craving is elicited by conditions associated with theavailability or use of the substance, such as watching someone else useheroin or light a cigarette or being offered some drug by a friend.

Cues induce memories of drug-induced euphoria are more importantfor stimulating craving and in predisposing to relapse.

Withdrawal Syndromes and Negative Reinforcement

Aversive withdrawal phenomena and negative reinforcement is equallyimportant, or even dominant in substance use.

Eg …in people who become dependent on benzodiazepines in thecourse of treatment for anxiety syndromes, when drug use isinterrupted, some seem to experience a reappearance of the originalsymptoms, whereas others have new distressing symptoms indicatingwithdrawal. The use of benzodiazepines alleviates both kinds ofaversive states.

The alcoholic, the heavy smoker, and the heroin user may experience,simultaneously or sequentially, relief of withdrawal, a sense of ease,and perhaps alleviation of dysphoria and depression after takingsubstance.

According to classic theories, substance abuse is :

1. A masturbatory equivalent(some heroin users describe the initial“rush” as similar to a prolonged sexual orgasm),

2. A defense against anxious impulses, or a manifestation of oralregression (i.e., dependency).

Recent psychodynamic formulations relate substance use as areflection of disturbed ego functions (i.e., the inability to deal withreality).

As a form of self-medication, alcohol may be used to control panic,opioids to diminish anger, an amphetamines to alleviate depression.

Some addicts have great difficulty recognizing their inner emotionalstates, a condition called alexithymia(i.e., being unable to find words todescribe their feelings).

Stress, drug use and addiction Stress activates the same brain [reward] systems responsible for the

positive reinforcing effect of drugs It increases physiological sensitivity to drugs

It increases desire to improve mood with drugs after exposure to stress.

Stress more strongly predicts drug use when there is a psychiatricdisorder, poor parenting, family dysfunction, and adverseneighborhood characteristics.

Stress, lack of social supports, and poor coping skills predict early onsetand escalation of drug use, relapse, and treatment resistance.

Interestingly, Post-Traumatic Stress Disorder (PTSD) often precedesdrug use in girls, but occurs more often after drug use in boys.

Girls are at increased risk for substance abuse when exposed to thestressors of family violence and alcoholism.

Preventive Implications: Sex differences should be taken intoaccount in identifying factors that contribute to drug use and in thedevelopment of a prevention or treatment plan.

• Children exposed to stress and conflict in the home are more likely toManifest high levels of aggressive behavior, the strongest predictor oflater drug use and other risk behaviors

Girls are influenced by peers differently than boys:

More likely to use drugs if friends & partners are using or introducesdrugs to them.

Concerns about peer approval, depression and body image – allinterrelated – increase susceptibility to drug use in girls.

Mental Health Problems Mental Health Disorders are strongly linked to drug use and

dependence.

Internalizing Disorders (PTSD, Depression, Anxiety disorders, Bipolardisorder)

Brain responses are heightened in response to drugs.

Tendency to self-medicate the anxiety & depression this process causesdrug use.

Mental Health Problems Externalizing Disorders (Conduct Disorder, Attention Deficit

Hyperactivity Disorder, Oppositional Defiant Disorder, AntisocialPersonality Disorder)

Low level of arousal in these disorders is related to an insensitivity toconsequences and a need for more stimulation.

Heightens risk for continued drug use to relieve symptoms.

Tend to be resistant to substance abuse treatment.

Personality & Temperament

A difficult temperament and certain personality characteristics are consistently related to heightened risk for drug use.

Impulsivity

Aggressiveness

Sensation or novelty-seeking

Negative affect

Impaired judgment

High activity level

Risk taking tendencies

Lack of regard for negative consequences

Lack of pain avoidance responses

Abnormal levels of arousal in response to stress.

Normal adolescence is characterized by greater reward anticipation,sensitivity, and sensation seeking—particularly social rewards (e.g.,peer regard, gains in social status).

It follows that adolescence is the period during which drug use onset ismost common.

And, therefore, that adolescents with especially high levels of anycombination of these traits are at heightened risk.

Preventive Implications: These traits can be redirected throughpsychosocial means to decrease risk for drug use. Prevention programsmust be designed to specifically redirect this developmental track.

Social Cohesion = attachment to and satisfaction with theneighborhood

Involves trust and support for one another in a community

Maintains norms for positive social behavior

Associated with lower drug use and lower drug-related mortality

Discrimination and social exclusion have profound negative effects :Physical and mental health disorders, including drug use anddependence.

Substantial evidence indicates that changes in price and availability canalter the consumption of alcohol and tobacco.

Increase in sales outlets or an extension of sales hours increases theavailability of alcohol, consumption tends to increase.

When the cost of either alcohol or tobacco is increased in relation todisposable income (e.g.,by increased taxes), consumption decreases.

Availability and Health Professionals.

physicians, dentists, and nurses have far higher rates of dependence onDEA-controlled substances, such as opioids, stimulants, and seda-tives,than other professionals of comparable educational achievement.

Thank you

Stahl’s essential psychopharmacology.

CTP 9th edition.

DSM 5

ICD 10

Kaplan and sadock synopsis of psychiatry 10th ed.

The Genetic Basis of Addiction Chad Epps and Elizabeth Laura Wright,