Neuropsychology and Biological Psychology: PSYC 20004

Addiction
Angela Attwood

Objectives
LECTURE: ADDICTION
Defining addiction Biologial models Physical dependence (negative reinforcement) Conditioned tolerance Psychological dependence (positive reinforcement)

SUPPLEMENTARY: ISSUES IN ADDICTION

Is Addiction a disease?

Overview
Define addiction

Biological models
Physical dependence Conditioned tolerance Psychological dependence

Individual differences
Genetics Personality

Cognition
Disease

What is addiction?
Early emphasis:
physiological adaptation (withdrawal upon

abstinence)
More recently:
Compulsive disorder (i.e. loss of control over

behaviour)
No absolute definition no one fits all.
E.g., what is the role of craving, withdrawal, do we

include non-pharmacological addictions (e.g., gambling)?

ICD-10 clinical description

A cluster of physiological, behavioural, and cognitive phenomena in which the use of a substance or a class of substances takes on a much higher priority for a given individual than other behaviours that once had greater value. A central descriptive characteristic of the dependence syndrome is the desire (often strong, sometimes overpowering) to take psychoactive drugs (which may or may not have been medically prescribed), alcohol, or tobacco. There may be evidence that return to substance use after a period of abstinence leads to a more rapid reappearance of other features of the syndrome than occurs with nondependent individuals
Source:

ICD-10 Diagnostic guidelines

A definite diagnosis of dependence should usually be made only if three or more of the following have been present together at some time during the previous year:

A strong desire or sense of compulsion to take the substance; Difficulties in controlling substance-taking behaviour in terms of its onset, termination, or levels of use; A physiological withdrawal state when substance use has ceased or have been reduced, as evidenced by: the characteristic withdrawal syndrome for the substance; or use of the same (or closely related) substance with the intention of relieving or avoiding withdrawal symptoms; Evidence of tolerance, such that increased doses of the psychoactive substance are required in order to achieve effects originally produced by lower doses (clear examples of this are found in alcohol- and opiate-dependent individuals who may take daily doses sufficient to incapacitate or kill nontolerant users); Progressive neglect of alternative pleasures or interests because of psychoactive substance use, increased amount of time necessary to obtain or take the substance or to recover from its effects; Persisting with substance use despite clear evidence of overtly harmful consequences, such as harm to the liver through excessive drinking, depressive mood states consequent to periods of heavy substance use, or drug-related impairment of cognitive functioning; efforts should be made to determine that the user was actually, or could be expected to be, aware of the nature and extent of the harm. http://www.who.int/substance_abuse/terminology/definitio n1/en/

Physical Dependence
Characterised by
Withdrawal syndrome upon abstinence Tolerance to the drug effects Is a model of negative reinforcement

Two models of physical dependence

Physical adaption Conditioned withdrawal
Initial use Maintenan ce Dependen ce Withdraw al Relapse

Physical adaptation
Biological changes occur to compensate for

repeated drug administration

Pharmacodynamic: e.g., receptor up/down

regulation Pharmacokinetic: e.g., enzyme synthesis

Long lasting, but reversible.

Results in:
Tolerance Withdrawal

Conditioned tolerance
Learning mechanism involving classical

conditioning

Conditioned tolerance/withdrawal model

Learning mechanism involving classical

conditioning Based on maintaining homeostasis Drug stimuli become signals for drug administration Acquire ability to induce tolerance and withdrawal

? =

Experimental evidence - animals

Siegel (1975)
DV: pain sensitivity (time to first paw lick) Days 1-3 Rats A administered morphine in test (hot plate) environment Rats B administered morphine in home environment Day 4 Rats administered morphine in test environment

Rats A but not B showed tolerance to morphine-

induced analgesia (i.e., reduced latency to paw lick)

Whole story ....?

Not all abused drugs induce a strong physical

dependence syndrome (i.e., withdrawal)

Doesnt explain why people take drugs in the first

place
Fails to explain relapse after withdrawal

Psychological dependence
Based on positive reinforcement Biological basis A behaviour that is followed by an appetitive

stimulus will be reinforced (and therefore repeated)

Psychological dependence
Addictive drugs are positive reinforcers Many widely abused drugs are self-administered

in animals (there are exceptions)

Addiction occurs due to the rewarding/euphoric

effects of a drug, but what underlies this?

Mesolimbic DA (reward) pathway

DA neurons project from VTA to NAcc and FC, all

of which are believed to be important in motivation ML DA system proposed to be involved in the regulation of biological drives and motivation Activated by natural reinforcers (e.g., food, sex)
Although natural reinforcers and drugs of abuse come in all shapes and sizes they have one physiological commonality: they all increase dopamine activity in this system (particularly NAcc)

Reinforcement interval
The most potent reinforcement occurs when it

immediately follows the response

Most addictive drugs have immediate effects Explains why users continue to use drugs despite

long-term negative consequences

The dependence process

Taken from Grilly: Drugs and Human Behavior

The disease model

Defines addiction as a medical disorder
(Ill-defined) CNS structural or chemical abnormality Biological (e.g., genetic) predisposition Triggered by environmental events

Emphasises loss of control over behaviour

(compulsions)
+ Seems to capture essence of addiction

- Biological basis ill-defined

- Implies addict is passive onlooker with no

control

Theories of addiction
Rational choice Self-medication Disease Self-efficacy Impulse control

Associative learning
Incentive sensitization Social learning... Reading if interested: Theory of Addiction

Robert West

Individual differences
Not everyone who takes a drug becomes

addicted
Self administration paradigms (rodents)

Not all rats selfadminister nicotine

Evidence of alcohol-preferring rodents

Biological vulnerability
Genetics

Personality traits
Cognition Disease

Genetics
Genes encode for several important aspects of

biology relevant to addiction. For example:

Enzymes that interact (e.g., metabolise) a drug Receptor number or density

Example
Nicotinic Acetylcholine Receptors (nAChRs)
Ach = endogenous ligand Nicotine is also an agonist Comprised of 5 subunits (/)

arranged around a central pore

Example: genetics and smoking

Example: genetics and smoking

This variant in 5 subunit gene is a missense mutation results in amino acid change in the 5 subunit protein. Definite functional significance changes the response of the receptor, as assessed using a nicotine agonist (Bierut et al., 2008).
Version 1. G allele. Normal response to nicotine. Version 2. A allele. Poorer response to nicotine. This version increases risk for heavy smoking/nicotine dependence.

Individual differences in pharmacodynamics

Personality traits
Impulsivity
Both a determinant and consequence of addiction

IMPULSIVITY
Frontal impairment Drug use

DEPENDENCE

Impulsivity
Multi-dimensional construct
Inability to delay, risky inappropriate ill-reasoned

behaviour, insensivity to negative consequences, difficulty in withholding (prepotent) responses.

de Wit (2008)

Measuring impulsivity
Subjective self-report (e.g., Barratt Impulsivity

Scale)
Behavioural measures: e.g., impulsive decision

making, behavioural inhibition

GO

NO-GO

Impulsivity and drug use

Impulsivity...risk factor
Longitudinal (and cross sectional) studies implicate

impulsivity as a risk factor for drug use and abuse

Impulsivity...higher in drug users
Impulsivity higher in individuals with a history of

drug use/abuse compared to non-user controls

Impulsivity...increased by drugs
Some drugs of abuse increase state impulsivity

(e.g., delay discounting, stop signal/go-nogo)

See de Wit 2008

Cognition
Executive function (including behavioural control)

Motivation
Attention (e.g., attentional biases for drug cues) Implicit cognitions Learning and memory Dependence is characterised by a move from

impulsive to compulsive drug use.

But what underlies this?

Compulsivity
Continued drug use can induce neural changes

that move individual towards compulsive use

Manifest as habitual (rather than goal-directed) Pathological learning building of drug-stimuli

associations
Sensitisation of reward systems

Cognitive withdrawal
Due to long-term effects on the brain, drug

abstinence can come to elicit negative consequences

Attention deficits

Reduced cognitive control

Negative biases (apathy) Impaired working memory

Smoking, working memory and COMT

Loughead et al. (2009)

VAL allele greater risk of smoking

Smokin g

Smoking enhances WM

COMT

WM

MET allele associated with enhanced WM performance Hypothesis: The high activity (VAL) allele will be a risk factor for detrimental working memory performance during nicotine abstinence

Hypothesised effects of smoking by genotype

Val carriers before smoking Val carriers after smoking Met carriers before smoking Met carriers after smoking

Pre-frontal dopamine

Loughead et al. (2009) Results (1)

Disease
Smoking prevalence is high in many psychiatric

disorders (schizophrenia, depression, psychological distress, ADHD)

Why? Self-medication?

High impulsivity/impaired cognition

Symptoms? See Gouldcauses? 2010 Co-morbid

Shared genetic vulnerability? (e.g., de Leon &

Diaz 2012)
Stress/low mood

Susceptibility to rewarding effects

Some people may be particularly sensitive to

reward
Due to differences in reward pathways in the brain Related to dopaminergic activity May influence take up of drug and/or maintenance

of use Possible role in schizophrenic smoking prevalence

(see Saqud et al. 2009 Smoking and Schizophrenia)

Phases of drug use

Initiation

Maintenance
Dependence Withdrawal Relapse Susceptiblility to specific drug or addiction more

generally

References (textbooks)
West (2006) Theory of Addiction. Blackwell

publishing Meyer (2005) Psychopharmacology: drugs, the brain and behaviour. Sinauer Associates Inc. Munaf & Albery (2005) Cognition and Addiction. Oxford University Press

Further reading
Crews & Boettiger (2009) Impulsivity, frontal lobes

and risk for addiction. PBB 93: 237-47 de Wit (2008) Impulsivity as a determinant and consequence of drug use: a review of underlying processes Gould (2010) Addiction and Cognition. Addiction Science and clinical practice 5: 4-14 Kreek et al. (2005) Genetic influences on impulsivity, risk taking, stress and vulnerability to drug abuse and addiction. Nature NS 1450-7 Saqud et al. (2009) Smoking and schizophrenia. Psych. Dan. 21: 371-5