1

PSY3032:

SUBSTANCE-RELATED DISORDERS

Dr. Joshua B. B. Garfield

Eastern Health Clinical School and Turning Point

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Reading
REQUIRED READING
Kring, A.M., Johnson, S., Davison, G.C.
and, 13th Ed., NY: Wiley. Neale, J.M.
Abnormal Psychology
Chapter 10 Substance Use Disorders

Case Study Assessment

CASE STUDY ASSESSMENT Oltmann,
T.F., Martin, M.T., Neale, J.M. &
Davison, G.C. (2014).
Case Studies in Abnormal Psychology.
10th edition. John Wiley & Sons, Ltd.

Chapter 9
Alcohol Use Disorder
Page. 250
After reading and understanding this case study,
your weekly assessment involves an online quiz
evaluating your understanding of this case.

*** Please note that Quiz 10: Alcohol

Dependence is open from the 26th
September at 9am (AEST). This quiz is
due on Friday 21st October at 4 pm
(AEST) ***
4

Global Problem of Psychoactive Drug Use

World Health Organisations 2009 Global Health Risks report:

Substance use causes 12.6% of deaths: Tobacco: 8.7% (2nd-leading risk factor); Alcohol:
3.6% (8th-leading risk factor); illicit drugs: 0.4%.

Substance use responsible for 9% of global burden of disease: Alcohol: 4.5% (3rdleading risk factor); Tobacco: 3.7% (6th-leading risk factor); Illicit drugs: 0.9% (18th-ranked
risk factor).

Australian Institute of Health and Welfare Drugs in Australia 2010 report:

Tobacco is the leading cause of death in Australia, responsible for 8% of national burden
of disease, costing society $31.5 billion annually

Cost to society of alcohol use estimated at $15.3 billion annually. Heavy drinking
responsible for 2% of national burden of disease (beneficial effects of light drinking
estimated to reduced national burden of disease by 1%, but methodology disputed).

Illicit drug use responsible for 2% of national burden of disease (mainly due to hepatitis
C transmission), and $8.2 billion in annual costs.

Prevalence of substance use disorders

4.9% of global adult population have an alcohol use
disorder (Gowing et al., 2015)
0.6% of global adult population have illicit drug use
disorders (UN Office on Drugs and Crime, 2012)
5.1% of Australians had a past-year substance use
disorder (not including tobacco) (Australian Bureau
of Statistics, 2007)
22.5% of adults in the world smoke tobacco (Gowing
et al., 2015)

Long History of Drug Use

in Human Societies
Alcohol: 8,000-12,000 years
Coca: Up to 8,000 years

Cannabis: over 4,000 years

Opium: Around 6,000 years
Tobacco: at least 3,000 years
Only Inuit have no record of traditional drug use
Most, if not all, societies integrate drug use into accepted,
sometimes ritualistic, cultural patterns of behaviour, and everyday social interaction.

Historical limits to extent of drug use

Prior to the advent of global trade,

geography limited the use of many drugs

Cultural norms and taboos
Inability to extract, preserve, and/or
synthesise active substance

Expansion of drug use

Colonialism and global trade:
Cash crops (e.g. opium, tobacco)
Opium wars
Increased availability of distilled liquor

Scientific advances:
Extraction and purification of active
ingredients (e.g. cocaine, morphine)
Synthesising new substances (e.g. heroin)

10

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Reaction to widespread
substance use
Widespread intoxication was incompatible with modern industrys need
for a disciplined, productive work force.
Xenophobia and moral panics:
Demonisation of Chinese opium dens in US West, Australia
Association of marihuana with illegal Mexican immigrants in USA
Social movements: temperance
Legislative control, prohibition

... But some kept using substances anyways!

Concept of addiction emerged:
substance abuse as a disease

Efforts to define, treat

13

Substance dependence:
The Medical Model

Drug dependence is seen as chronic and

relapsing sickness or disease
Removes responsibility from abuser - not
weak-willed, but sick

Widely accepted, though support for a

discrete and specific disease category from
scientific, clinical, and sociological research is
unclear.

14

DSM-5 substance use disorder

1. Recurrent substance use resulting in a failure to fulfil major obligations (e.g. at work or school, or care for
children)

2. Recurrent use in situations where it may be physically hazardous (e.g. driving)

3. Persistent cravings to use the substance
4. Continued use despite it causing recurrent interpersonal problems (e.g. fights or arguments)
5. Frequently using more of the substance, or using for longer periods of time, than intended
6. Persistent desire, or repeated unsuccessful efforts, to cut down or cease

7. Large proportion of ones time spent obtaining, using, and/or recovering from effects of substance
8. Important social, recreational, or occupational activities given up or reduced because of substance use
9. Substance use continued despite knowledge of physical or psychological health problems caused by substance
10. Tolerance (needing more of substance than previously to achieve same effects and/or diminished effects from
using previously effective amount)

11. Withdrawal symptoms when substance use reduced or ceased (symptoms depend on type of substance)
Severity defined by number of symptoms:

Mild: 2-3 of the 11 symptoms listed above

Moderate: 4-5 symptoms

Severe: 6 or more symptoms

15

ICD-10 substance dependence

At least 3 of following criteria:
1.

Strong desire or compulsion to use

2.

Difficulties controlling onset, termination, or level of use

3.

Withdrawal syndrome when use reduced or ceased

4.

Tolerance

5.

Increasing neglect of alternative pleasures or interests because of

use or because of increased amount of time necessary to obtain
substance or to recover from its effects

6.

Persisting with use despite experiencing harmful consequences

(physical or mental health; cognitive impairment) and being aware
that these were being caused or exacerbated by substance use.

16

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The biopsychosocial model

Drug effects are an interaction of:

The substance (type of drug, dose, purity,

adulterants, route of administration)
The user (physiological and psychological
state)
The context (social and physical context)

This is frequently referred to as the drug, set

and setting model (Zinberg, 1986)

18

Set
Physiological:
age, body weight, sex
genetics
circadian rhythms, health
expression of neural receptors, transporters, transmitters
Psychological:
Mood
Beliefs regarding drug usage and its consequences (e.g. usage
is inversely proportional to perceived harm)
personality traits

19

Setting
Physical Environment: effects in hospital vs. at a party
Social Environment, e.g. type of society
Cultural and legal norms: religious taboos; parents
attitude; condoned use of certain drugs; social support
and sanctions for appropriate and inappropriate
behaviour

Peer behaviour: compare our behaviour with others,

learn rules and rituals
Peer-group identification

Medias portrayal of drug use/ advertising

Popular culture

20

Drug
Route of administration
Rate of administration (e.g. sipping vs. sculling)
Quantity (dose)
Characteristics of drug:
Pharmacodynamics:
rate of metabolism
rate its absorbed into blood stream (depends on route of administration)
rate it crosses blood-brain barrier

rate of elimination from body

Pharmacology:
what receptors, transporters, ion channels, etc. it attaches to
(partial or full) agonist, antagonist, (partial or full) inverse agonist, reuptake
inhibitor, reuptake enhancer, reuptake reverser
effects in brain vs. effects in periphery

21

Alcohol: Ethyl Alcohol (ethanol)

Agonist at GABAa benzodiazepine receptor sites
Inhibits ion channels (sodium, calcium, potassium) that facilitate
excitatory neurotransmission
Inhibits glutamate receptors (AMPA, kainate, and, at high doses, NMDA)
Inhibits adenosine reuptake
Various other actions, e.g. at some serotonergic and cholinergic receptor
sites
The blood alcohol concentration (BAC) is determined by:

Concentration of alcohol in drink, rate of drinking

Presence of food in stomach

Body size

Sex

22

Alcohol Effects:
Low doses (below 0.1% BAC):
Disinhibition (consequences are specific to person and surroundings;
relaxed, euphoric, withdrawn, or aggressive)

Expectancy effects (only with low doses)

Increased talkativeness, sociability
Impaired judgment, attention, self-control, information processing,
reaction time
Impaired muscle coordination
Increased heart rate, reduced body temperature
Increased urination
Sleepiness

23

Alcohol Effects
High doses: blood alcohol content (BAC) > 0.15%:
disorientation, confusion, slurred speech,
blurred vision, poor muscle control
nausea/vomiting (particularly in newer drinkers)
decreased testosterone (and decreased sexual
response)
BAC > 0.3:

stupor, sleep, unconsciousness, coma, death

24

Chronic Heavy Alcohol consumption

CNS
Peripheral Neuropathy

Reproductive:

Alcoholic Dementia

impaired sexual desire or

arousal

Wernicke-Korsakoffs
syndrome

Impotence or testicular
atrophy (men)

Cardiovascular
Hypertension

Haematological- Macrocytic
Anaemia

Strokes

Musculoskeletal- Myopathy
with Chronic weakness

Cardiomyopathy

Endocrine

Arrythmias

Dermatological

25

Effects of Chronic Heavy Drinking

Gastrointestinal:
Oesophagitis
Gastritis
Peptic ulcer disease
Malabsorption
Gastric cancers

Pancreas:
Pancreatitis- Acute &
Chronic
Cancer

Liver:
Fatty liver changes
Reversible with abstinence
Alcoholic hepatitis - (i.e.,
damaged hepatocytes).
Cessation likely to lead to
recovery.
Cirrhosis Liver cells die
and are replaced by fibrous
scar tissue
Hepatocellular Carcinoma

26

Alcohol: Wernicke-Korsakoff
Syndrome

A brain disorder involving loss of specific brain functions

caused by a thiamine (vitamin B1) deficiency .
Generally attributed to malnutrition. Symptoms may be
exacerbated by alcohol withdrawal.
The syndrome includes two separate sets of symptoms.
Wernicke's encephalopathy involves damage to multiple nerves
in both the central and peripheral nervous systems.
Korsakoff syndrome involves impairment of memory out of
proportion to problems with other cognitive functions due to
damage to areas of the brain involved with memory.

27

Alcohol: Wernicke-Korsakoff
Syndrome - Symptoms

Vision changes (including double vision, eye movement

abnormalities, eyelid drooping)
Loss of muscle co-ordination
Unsteady, uncoordinated walking

Loss of memory, can be profound

Inability to form new memories
Confabulation (making up stories to fill lapses in memory of
events; often not conscious of this)
Hallucinations

28

Alcohol Brain Damage

Excessive consumption of alcohol

leads to damage to myelinated neurons
(white matter).
Women show a greater sensitivity to
alcohol neurotoxicity than do men.
(Hommer, Momenan, Kaiser, Rawlings,
2001)
Cigarette smoking can exacerbate
alcohol-induced damage (Durazzo,
Gazdzinski, Banys, & Meyerhoff, 2004)
Increased brain volume and improved
cognitive function with several months
or years abstinence (Yucel, Lubman,
Solowij, & Brewer, 2007)

29

Alcohol withdrawal
Autonomic hyperactivity (sweating, racing heart)
Shaking hands
Nausea
CNS excitability:
Anxiety, agitation
Seizures in severe cases (can be life-threatening)

Delirium Tremens (DTs):

profound confusion, delusional states, fluctuating consciousness,
hallucinations

Treated with other CNS depressants such as benzodiazepines

30

Benzodiazepines
Diazepam (valium,
valpam)

Flunitrazepam
(Rohypnol)

Alprazolam (xanax)

Temazepam
(normison, temaze)

Clonazepam (klonipin,
rivotril)
Nitrazepam
(mogadon)

Oxazepam (serapax,
murelax)

Lorazepam (Ativan)
Triazolam (halcion)
Chlordiazepoxide
(Librium)
Midazolam

31

Benzodiazepines
Agonists of the benzodiazepine site on the
GABAA receptor

Increase ability of GABA to activate GABAA

receptor, enhancing inhibitory neurotransmission
Z drugs have different chemical structure,
but similar pharmacological activity.
Zolpidem (stilnox, ambien)
Zopiclone (imovane)

32

Benzodiazepines
Replaced more dangerous barbiturates for most
clinical applications during 1960s-70s
Anxiolytic: stop panic attacks
Anti-convulsant: control of seizures
Hypnotic: insomnia

Muscle relaxant
Occasionally used in anaesthesia
Reduce alcohol and opioid withdrawal symptoms

Rapid, high tolerance should limit long-term medical

use, but often doesnt

33

Benzodiazepine acute effects

Relaxation, loss of inhibition, euphoria
Sedation, lack of muscular coordination

Cognitive impairment
Amnesia

Enhances effects of alcohol, opiates

Overdose: respiratory depression, coma,
cardiac arrest

34

Benzodiazepine chronic
effects
Cognitive impairment
Extreme tolerance
Paradoxical effects, e.g. increased anxiety
Withdrawal:
Similar to alcohol withdrawal syndrome
Extremely dangerous and prolonged:
Acute symptoms last up to 2 months
Residual symptoms can last 6-36 months
Re-emergence of severe withdrawal after single use many months
after cessation

35

Nicotine
Primary psychoactive ingredient in tobacco: accounts for the acute
pharmacological effects of tobacco and the subsequent dependence on
cigarettes.
Numerous chemicals in tobacco smoke. Nicotine has some harmful effects, but
most harmful effects of tobacco smoking are due to other chemicals.

Agonist at nicotinic acetylcholine receptors

Effects in central and peripheral nervous systems, heart, and cardiovascular
system
Brain areas activated by nicotine include:
Locus coeruleus (behavioural arousal and vigilance)
Frontal lobes and cingulate gyrus (cognition, working-memory, attention,
motivation, mood, and emotion)

36

Nicotine behavioural, cognitive,

and psychological effects

Increased concentration
Improved working memory

Improved performance in vigilance and rapid

information processing tasks
Relaxation
dizziness (in non-tolerant smokers)

Smokers unconsciously self-titrate to optimize nicotine

levels and keep them at steady-state.

37

Nicotine: Consequences of
tobacco use - Toxicity

Smoking causes 4.3 million deaths annually.

It is the tar in tobacco that leads to much of the long-term

toxicity
Lung cancer, non-cancerous lung diseases, cancers of other body
organs, heart and cardiovascular diseases.
It is estimated that 14 min of life is lost for every cigarette smoked
One in every six people who try smoking will eventually die of a
smoking-related illness.

Serious health risks associated with passive smoking

Increased risk of spontaneous abortion, stillbirth, preterm delivery,
retarded intrauterine growth and early postpartum death when smoking
occurs during pregnancy.

38

Nicotine: Consequences of tobacco

use - Dependence on nicotine
Smoking does not appear to lead to nicotine tolerance
(except for tolerance to dizziness/nausea/vomiting)
However, clear physiological and psychological dependence
does develop
Withdrawal is characterized by:

severe craving for nicotine

irritability, anxiety, anger, restlessness, impatience
difficulty in concentrating
increased appetite, weight gain
insomnia

39

Cannabis
Two species:

Cannabis sativa

Cannabis indica

Also known as marijuana or hemp

Numerous preparations (e.g. marijuana buds,
leaves, hashish, hash oil, wax, etc.)
ROAs: smoking, eating, drinking, vapourisation
Major psychoactive ingredient is 9tetrahydrocannabinol (9-THC)
Several other cannabinoids modify THCs effects
(e.g. cannabidiol)
THC content ranges widely

40

THC effects
Agonist at cannabinoid receptors:
CB1:
Widely expressed throughout brain
Often located presynaptically, inhibits transmitter release (both
excitatory and inhibitory)
Appears mainly responsible for cannabis psychological effects (e.g.
on anxiety, cognition, perception)
CB2:
Mainly expressed peripherally (e.g. immune system cells, peripheral
nerve cells)
Effects on immune system function, inflammation, pain perception
Unclear if significantly contributes to psychological effects

41

Cannabis Acute Effects

Smoked or vapourised: 2-6 hours; eaten: 4-24
hours
Impaired attention & short-term memory, altered
sensory awareness, altered motor control and
posture
Hallucinogenic at high doses in some users
Analgesic, anti-inflammatory, appetite stimulant,
anti-emetic and other medical applications

Drop in blood pressure

42

Cannabis: Effects of long-term

heavy use
Dose-related decline in IQ scores in adolescent-onset heavy long-term users, but not
adult-onset users (Meier et al., 2012).
Impaired attention, verbal memory, working memory, and information filtering and
processing speed (e.g. Schweinsburg, Brown, & Tapert, 2008).
Conflicting data regarding degree to which recovery occurs with abstinence (e.g.
Hanson et al., 2010; Meier et al., 2012).
Reduced hippocampus and amygdala volume with very long-term, heavy daily use
(Yucel et al., 2008).
Precipitation of onset, or intensification of, underlying psychotic, mood, or personality
disorders.
Increases likelihood of developing psychotic disorders if used heavily during early
adolescence.
Frequency-of-use-dependent reductions in likelihood of high school and university
completion, and increased likelihood of other illicit drug use and suicide later in life in
those who start using prior to age 17 (Silins et al., 2014).

43

Cannabis withdrawal
Generally mild in all but the most heavy users, suggesting that strong
physical dependence does not easily develop. Symptoms usually last
1-2 weeks and include:
Anger/irritability/aggression
Depressed or intensified moods
Restlessness, anxiety
Loss of appetite
Insomnia, vivid dreams
headaches
stomach cramps
sweating, fever, chills

44

Synthetic cannabinoids
Dozens of new chemicals have emerged in recent years
Sprayed onto non-psychoactive herbal materials (marketed as, legal
highs, e.g., spice, kronic, k2, etc.) or sold in powder form on internet
Little or no scientific testing in humans
Recent reports of much more harmful effects than natural cannabis:

Seizures
Reports of fatal overdoses, heart attacks
Psychotic episodes

More severe, prolonged withdrawal symptoms in dependent users

Full agonists vs. partial agonists

45

Opioids
Natural: opium, morphine, codeine
Semi-synthetic: heroin, oxycodone, buprenorphine, etc.
Synthetic: methadone, fentanyl, tramadol, pethidine,
etc.

Agonist at opioid receptors (m, d, k)

Clinical Uses: Pain (analgesia), Anti-tussive (prevents
cough), Slows bowel (stops diarrhoea), Anaesthesia

Side-effects: Pupil constriction, nausea, vomiting,

constipation, reduced immunity, depressed respiration,
itching

46

Opioids recreational effects

Euphoria, Rush
Emotional detachment

Sense of comfort, elimination of anxiety

and other negative emotions
Nod: dream-like sedation (high doses)
Stimulation in some tolerant users

47

Opioid overdose
Severe respiratory depression

Leading cause of death among opioid-dependent

people
Usually not opioid alone, but in combination with
another depressant drug (e.g. alcohol,
benzodiazepines)
Especially dangerous after reduced tolerance:
Relapse
Release from prison

Contextual change

48

Opioid Chronic effects

Impaired immune system function
Reduced testosterone levels in men:
Reduced sex drive

Increased risk of osteoporosis

Reduced muscle strength

Chronic constipation

49

Opioid withdrawal
Chills, sweating, cramps, nausea, watery eyes & nose,
yawning, severe anxiety and agitation, insomnia.
Duration depends on drug:

3-7 days for heroin

Up to 1 month for methadone
Post-acute withdrawal syndrome: Acute
withdrawal sometimes followed by depression,
insomnia, anhedonia, cravings, anxiety lasting
several months

50

Stimulants
This category includes drugs such as cocaine and the
amphetamines
Also methylphenidate (Ritalin, Concerta)
More recently: cathinones and other synthetic drugs
(sometimes marketed as bath salts or synthetic
cocaine)
Primary mechanism of action in CNS: Increase
dopaminergic activity:
Cocaine: inhibits re-uptake of dopamine

Amphetamines: increase dopamine release

51

Cocaine
Used medically as a local anaesthetic.
Used traditionally (chewed coca leaves)
by indigenous people of Andes to reduce
fatigue and hunger.

Crack is smokable freebase form.

Effects last from a few minutes to 1
hour.

52

Amphetamines
Amphetamine :
Used in the treatment of narcolepsy and ADHD (dexedrine,
dexamphetamine, adderall)
Illicitly marketed as speed, or illicitly diverted
pharmaceutical amphetamine (dexies)

Methamphetamine:
Similar medical applications as amphetamine (desoxyn)
Illicitly, can appear as speed, base, or ice
Effects last up to 12 hours
More neurotoxic than amphetamine or cocaine

53

Stimulant acute effects:

Increased alertness, energy, insomnia

Euphoria, confidence, grandiosity

Decreased appetite.

Prolonged use or high doses: anxiety,

agitation, paranoia, psychosis
Increased blood pressure, heart rate
Overdose can cause stroke or heart attack

54

Stimulant chronic effects

Heart disease
Dental problems from tooth grinding

Route of administration-dependent effects:

crack lung or meth mouth from smoking
nasal damage from snorting cocaine
abscesses from frequently injecting cocaine

Methamphetamine: neurotoxicity leading to

Parkinsons disease, cognitive deficits
Prolonged psychosis

55

Stimulant withdrawal
hypersomnia, lethargy, and fatigue
apathy, depressed mood
increased appetite

irritability, anxiety, agitation

Lasts several days to several months,
depending on duration and amount of
use

56

MDMA
Ecstasy or molly
Occasionally used in psychotherapy in 1970s and 1980s
before being banned.
Recent experimental use as treatment for PTSD
Closely-related drugs: MDA (metabolite), MDEA
Releases serotonin and other monoamines (dopamine and
noradrenaline), activates 5-HT1 and 5-HT2 receptors

empathogen or entactogen; combination of stimulant

and psychedelic effects

57

MDMA neurotoxicity
Serotonin neurotoxicity: likely to be exacerbated by
hyperthermia (especially use in crowded environments,
prolonged dancing):
Impaired verbal and visual memory
Impaired decision-making (executive functioning)
Greater impulsivity and lack of self-control
Sleep disturbance
Depression and anxiety

Deficits may persist up to a year following frequent, heavy use.

58

Hallucinogens
3 classes: psychedelics, dissociatives, deliriants
Illusions, intensification or distortion of perception,
elementary and complex visual hallucinations,
synaesthesia
Intense changes in mood and thought processes,
introspection, psychosis in some users

Distorted sense of time

ego dissolution: reduced sense of self

59

Hallucinogens: psychedelics
LSD, psilocybin mushrooms, DMT (Ayahuasca), mescaline
(peyote), 2CB, 25i-NBOMe
Agonists at 5HT-2a receptor
Tolerance develops, but addiction extremely rare
Traditional use in mystical practises; use in 1950s and 1960s for
treatment of addiction and other psychotherapeutic applications;
Current small studies of psychotherapeutic applications
Overdose death rare or non-existent with older psychedelics,
though some newer ones appear more physiologically dangerous
(e.g. NBOMe series)

60

Hallucinogens: dissociatives
NMDA receptor antagonists:
Ketamine, PCP, DXM, nitrous oxide
Some used medically as anaesthetics
Ketamine used to treat depression and pain
Addictive, range of physical, neural, cognitive, and
psychiatric harms
Kappa opioid agonists:

Salvia divinorum: non-addictive, may be anti-addictive

61

Hallucinogens: deliriants

The true hallucinogens: Datura, belladonna

alkaloids (e.g. scopolamine, atropine),
diphenhydramine
Antagonists at muscarinic cholinergic receptors

Some used (at very small doses) to treat motion

sickness, insomnia, applications in anaesthesia
High toxicity and unpleasant physical and mental
effects limit recreational use:
hyperthermia, tachycardia
prolonged, often frightening delirium

62

Solvent and volatile

hydrocarbon inhalants

Used industrially as solvents, propellants, fuels (e.g.

in petrol, paint, paint thinner, aerosol sprays,
industrial cleaning agents):
Toluene: present in some types of glue, spray paint, petrol
Butane: lighter fluid

Mixture of depressant and deliriant effects

Acute dangers:
Hypoxia
Sudden sniffing death: sensitisation to adrenaline,
leading to heart attack

63

Solvent and volatile hydrocarbon

inhalant: long-term effects
Brain damage from repeated hypoxia

Heart disease
Specific to chemical:
Toluene: demyelination (white-matter damage): severe,
long-lasting neuropsychological impairment (cognitive,
movement, etc.)
Carbon tetrachloride: potent liver toxin

Benzene: carcinogenic, bone marrow toxin

Recovery from neural impairments may take years, and may
not be complete in most severely affected.

64

Classical (Pavlovian) conditioning

Unconditioned stimulus (US: drug effects) becomes associated with temporally
proximal conditioned stimuli (CSs: physical context, drug paraphernalia, people with
whom drugs are used)

CS alone can then elicit:

Conditioned A state: drug-like physiological and psychological effects:
Placebo response to denicotinised cigarette
Alcohol expectancy effects.
The needle freak phenomenon

Conditioned B state: conditioned tolerance, withdrawal:

Withdrawal-like symptoms in opioid users exposed to opioid-related stimuli
Drug-taking in a new environment may trigger overdose due to lack of cues to
signal onset of drug effect.

Addiction established in one context may not generalise to very dissimilar context:
e.g. USA soldiers heroin use in Vietnam in 1960s/70s

Discomfort of withdrawal may also act as a US

65

Operant (instrumental)
conditioning
Positive reinforcement (achieve reward):
Action (drug seeking, use) leads to drug effects
If reinforced (pleasant effects) probability of repeating the action increases, if
punished (feel ill) probability decreases

Negative reinforcement (escape unpleasantness, physical or psychological):

Action (drug use) in response to anxiety, withdrawal symptoms
If reinforced (symptoms relieved), probability of repeating the response increases

Environmental stimuli can control operant behaviour:

Stress may reinstate an instrumental response thats been extinguished.
Pavlovian-instrumental transfer and cue-induced reinstatement: Classicallyconditioned stimuli can energise instrumental responding, even after extinction.

66

Biological models of substance

dependence
Incentive-sensitisation hypothesis (Robinson & Berridge, 1993, 2000):
Repeated stimulation of dopaminergic pathways by drugs leads to
hypersensitivity to drugs and associated cues (sensitisation)
Beyond-normal excitability to even mildly-associated cues,
memories, etc., leads to easily-induced, long-lasting cravings

Desire for drug is independent of actual liking, tolerance, or

withdrawal
Human users of opioids and cocaine show heightened neural and
attentional response to drug-related imagery some studies find
association with relapse.

67

Striatal structures involved in learning

and maintenance of drug-seeking

Excitation of mesolimbic dopaminergic pathway (particularly from ventral tegmental

area to striatal structures) involved in learning associations between stimuli and
rewards:
Projection to nucleus accumbens shell signals reward value of stimuli, Energises
attention towards novel stimuli, rewards and associated cues, and response to these

Dorsomedial striatum involved in initial instrumental learning (associations

between action and outcome).
Basolateral amygdala and nucleus accumbens core involved in establishing control
by stimuli over drug-seeking behaviour

Addictive drugs high-jack this system, increasing activity related to drugs and
drug cues, reducing activation related to natural reinforcers.
Important in early stages of establishing addiction: Once established, glutamatergic
projection from prefrontal cortex to nucleus accumbens core maintains persistent
craving and responsiveness to drug-related cues, while dopamine in dorsolateral
striatum controls habitual/compulsive responding.

68

Final common pathway for drug

seeking

Kalivas & Volkow (2005)

69

Frontocortical dysfunction in
substance dependence

Hyper-activity in orbitofrontal cortex and anterior cingulate in response to

drug-related stimuli is similar to hyper-activity of these structures seen in
obsessive-compulsive disorder.
However, activity in these structures is reduced in cocaine and opiatedependent samples during:
Non-drug-related decision-making tasks
error-detection tasks
exposure to non-drug pleasant stimuli
Dual process model: addiction maintained by combination of sensitised
attention/approach bias to drug-related stimuli and impairments in
decision-making/cognitive control suggests cognitive training targeting
these dual deficits may assist treatment.

70

Striatal dopamine (type 2) receptor expression

Volkow, Fowler, Wang, and Goldstein (2002)

71

Drugs and the adolescent

brain
From puberty to late teens/early 20s:
Maturation of frontal and temporal regions involved in:
executive function
inhibitory control

affect regulation.
Drug use may disrupt this development, causing longstanding vulnerability to dependence

Adolescent brain may generally be more vulnerable to

adverse neuropsychological impacts of drugs.

72

Hedonic allostasis (Koob & Le

Moal, 1997)

73

Koob and Le Moal (2001)

74

Hedonic allostasis (Koob & Le

Moal, 1997)

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Hedonic allostasis in humans?

Anhedonia (reduced ability to feel pleasure):
Widespread in substance-dependent samples (Garfield, Lubman, &
Yucel, 2014)
May lead to drug use to self-medicate pleasure deficit
May reduce motivation to engage in activities that would compete
with drug use.
Predicts increased likelihood of relapse in tobacco smokers (Cook,
Spring, McChargue, & Doran, 2010; Cook et al., 2015).

Reduced response (subjective or neural) to pleasant imagery (e.g.

Dunning et al., 2011; Lubman et al., 2009):
Predicts increased likelihood of relapse in tobacco, alcohol, and
opiate users (Lubman et al, 2009; Heinz et al, 2007; Versace et al.,
2012)

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Capture rates by drug type

US National Co-Morbidity Survey (Anthony, Warner and Kessler, 1994)

77

Genetic influences on development

of substance dependence

Twin studies: Greater concordance for identical

twins than fraternal twins for:
Alcohol abuse (McGue, Pickens, & Svikis, 1992)
Tobacco smoking (True et al., 1999)
Heavy cannabis use (Kendler & Prescott, 1998)
Substance abuse in general (Tsuang et al.,
1998)

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Genes potentially involved in susceptibility

to substance dependence

Variations in genes coding for:

m opioid receptor: alcohol, opiates
Dopamine D2, D3, and D4 receptors; dopamine transporter; enzymes
involved in dopamine breakdown: alcohol, nicotine, opiates, stimulants
Tryptophan hydroxylase (serotonin precursor), Serotonin receptors 1b
and 2a, serotonin transporter: alcohol, opiates

GABAA receptor subunits: alcohol

Muscarinic acetylcholine receptor type 2: alcohol
Cannabinoid receptor type 1: alcohol, stimulants

Enzymes involved in alcohol metabolism: alcohol

Enzymes involved in nicotine metabolism: nicotine

79

Epigenetics
Change in function of gene, without change in gene
itself (DNA and histone methylation, acetylation,
phosphorylation, etc.)
Constant process: interaction with environment,
trauma, toxins, drugs. Changes last seconds to years.

Human research on prenatal exposure to:

Cannabis: associated with long-lasting changes in
dopamine receptor expression

Tobacco: associated with long-lasting changes in opioid

transporter expression

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Epigenetics and drugs in

rats
In adolescent rats, exposure to:
THC: long-term changes to expression of genes coding for an opioid
transmitter, increased heroin self-administration in adulthood
(Tomasiewicz et al., 2012).

Alcohol: changes in regulation of genes coding for dopamine and

glutamate receptors in adulthood. Exposure to alcohol in adulthood
only does not lead to same changes. (Pascual, Boix, Felipo, & Guerri,
2009)
Some changes can be transferred between generations (not clear how):
Morphine exposure in female rats in adolescence (before pregnancy)
changes dopamine receptor sensitivity of offspring (Byrnes, Johnson,
Carini, & Byrnes, 2013)

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Expectancy effects
Belief that a drug will have a certain effect
influences likelihood/amount of use:
Those who believe that alcohol will reduce stress
or increase social skills tend to drink more.

Rates of cannabis use in US adolescents who

perceived:
great risk: 1.8%

no, little, or moderate risk: 11.2%

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Personality factors
Sensation/novelty seeking
Negative affectivity
... But also high levels of positive
affectivity, when combined with
sensation/novelty seeking
Low constraint (cautious behaviour, harm
avoidance, conservative morality)

83

Social and cultural factors

Acceptability: e.g. wine-drinking countries (e.g. France,
Spain, Italy) vs. prohibitionist countries (e.g. Saudi Arabia,
Iran)

Social acceptability may differ by gender.

Availability (prevalence, cost, etc.)
Parental attitudes, substance use, monitoring of adolescents
behaviour and peer networks.
Peers attitudes and substance use
Relationship breakdown associated with onset of alcohol
abuse/dependence.
Advertising

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Environmental stress,
deprivation, and enrichment
Bruce Alexanders Rat Park experiments in 1970s:
compulsive morphine self-administration seen in
socially isolated rats in barren, unstimulating cages, but
little or no self-administration in rats housed in large
cages with other rats, toys, etc.

Moving rats from deprived to enriched environment

after establishment self-administration reduced
morphine use.
Inconsistent replication.

85

Rodent models of facilitation by stress of

learning drug self-administration
Food restriction increases self-administration of opioids, alcohol
Physical stress (tail pinch, electric shock, restraint): stimulants and
opioids; increased motivation to seek opioids in those already
trained to do so.
Social stress (aggression from dominant rats, mixed-sex housing,
social isolation): opioids, stimulants, alcohol

Witnessing another rat in distress: stimulants

Prenatal stress (restraint stress applied to pregnant mother rat)
increases stimulant self-administration in offspring
Source: Piazza & Le Moal (1998)

86

Rodent models of protective effects

of environmental enrichment
Enrichment reduces cocaine and nicotine and cocaine consumption in rats (Puhl, Bloon, Acosta-Torres,
& Grigson, 2012; Venebra-Munoz et al., 2014)

Reduced contextual preference conditioning by cocaine or heroin after prolonged enrichment in mice
(Solinas, Chauvet, Thiriet, El Rawas, & Jaber, 2008; Rawas, Thiriet, Lardeux, Jaber, & Solinas, 2009)
Enrichment during methamphetamine administration reduces later withdrawal symptom severity in
rats and desire to consume methamphetamine after withdrawal (Hajheidari, Miladi-Gorji, & Bigdeli,
2015a; 2015b)
Enrichment during extinction of alcohol context conditioning reduces later reinstatement or renewal
of cocaine- or alcohol-seeking (Thiel, Engelhardt, Hood, Peartree, & Niesewander, 2011; Li, Meng,
Huang, Wang, & Li, 2015)
Degree to which enrichment reduces amphetamine or cocaine self-administration varies according to
genetics in rats, and dose administered (Gipson, Beckmann, El-Maraghi, Marusich, & Bardo, 2011;
Meyer & Bardo, 2015)
Enrichment reduces brain stress response to nicotine withdrawal more strongly in female than in male
rats (Skwara, Karowski, Czambel, Rubin, & Rhodes, 2012)
Switching mice from enriched to non-enriched environment in young adulthood increases cocaine
contextual preference conditioning (Nader et al., 2012)

87

So what are risk and protective

factors? Prior to birth
RISK FACTORS
Family economic
deprivation
Sole parent household
Paternal genetic risk for
alcoholism
Maternal drug use in
pregnancy
Source: Loxley et al (2004)

PROTECTIVE FACTORS

88

So what are risk and protective

factors? Infancy and pre-school
RISK FACTORS
Environmental tobacco
smoke
Child neglect and abuse

Source: Loxley et al (2004)

PROTECTIVE FACTORS
Easy temperament

89

So what are risk and

protective factors? Age 4-11
RISK FACTORS
Early school failure
Conduct disorder
Aggression
Impulsiveness

PROTECTIVE FACTORS
Social and emotional
competence
Shy and cautious
temperament

90

So what are risk and protective

factors? 12-17 years
RISK FACTORS

PROTECTIVE FACTORS

Low involvement in activities with

Religious involvement

adults
Perceived and actual community
drug use
Community disadvantage and
disorganisation
Availability of drugs
Positive media portrayal of drugs
Parent-adolescent conflict
Favourable parental attitudes
towards drugs
Negative affectivity
Impaired behavioural inhibition

Family attachment
Low parental conflict
Parental or adult communication

91

Treatment of substance
dependence

Detoxification:
Inpatient programs often 1-2 weeks
Management of withdrawal symptoms
First step, but generally high relapse
rates if no further treatment

92

Tapering dose
Scheduled smoking with gradual reductions: good
success rates in those who adhere to program.
Necessary with benzodiazepines to avoid dangerous
withdrawal symptoms
Weaning off after stabilisation on opioid
pharmacotherapy

Relies on high motivation, self-control, distress

tolerance: High rate of relapse if done too soon, too
quickly, or without psychotherapeutic preparation

93

Relapse prevention
Giving up smoking is the easiest thing in the world. I
know because I've done it thousands of times.
Mark Twain
Causes of relapse: stress, physical and social context,
substance use (lapse)
Learning to anticipate risky situations
Learn from lapses to identify cause and prevent full
relapse.
Effective at reducing use in alcohol dependence,
only weak effect for nicotine.

94

Psychological and behavioural

treatments

Simply being interviewed about level of use can lead to reductions in use in some.

Cognitive Behavioural therapy: relapse prevention and replacing drug use with
new activities.

Contingency management:

Rewards contingent on abstinence, active avoidance of substance, treatment

adherence, adaptive behaviours, etc.

Effective for alcohol, cannabis, cocaine, heroin

Controlled drinking:

Alternative to abstinence-focused approach

Teaching techniques to moderate use, combined with social skills and relaxation
training

Demonstrated effectiveness for alcohol, but would this ever be trialled with other
drugs???

95

Rehabilitation and
therapeutic communities

Programs range from 1 month to 2 years

Isolation from drugs and drug-using social networks
(often rural locations)
Intensive group therapy (and individual psychotherapy
in some programs) to examine dynamics of addiction
Structured activities and responsibilities

High drop-out rate, benefits require long-term

commitment

96

Mutual support fellowships:

12 step programs
Main ones are Alcoholics
Anonymous and Narcotics
Anonymous

Marijuana Anonymous, Cocaine

Anonymous, Crystal Meth Anonymous,
and Nicotine Anonymous also present in
Australia

Spiritually-based, abstinenceoriented program of frequent

meetings, sponsorship of
newer members by older
members
Based on permanent disease
model of addiction.

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Who are the people who recover?

POSITIVE RECOVERY CAPITAL

NEGATIVE RECOVERY CAPITAL

Personal resources and skills selfesteem; self-efficacy; positive

expectancies; coping skills

Significant history of mental health

problems

Belonging and embeddedness

bonding and positive support from
family, peers, social/community
involvement

Partner, family and peer group

embedded in addiction

Safety and stability

Significant history of criminal

involvement

Pathways and ongoing availability of

opportunity

Lack of opportunity and access to

support

98

Medications for substance

dependence
Agonist substitution:
Opioids:
Methadone: full agonist

Buprenorphine: partial agonist

Pharmaceutical heroin in some countries

Alcohol, benzodiazepines:
Diazepam

Tobacco:
Nicotine gum, patches
e-cigarettes

99

Medications for substance dependence

Symptom reduction:

Acamprosate: Increases GABAergic transmission and reduces NMDA receptor

activity (for alcohol craving)

Baclofen: GABAB receptor agonist (for alcohol and benzodiazepine withdrawal and
cravings)

Clonidine: a2 adrenaline receptor agonist: sedative, lowers blood pressure & heart
rate (for physical discomfort associated with alcohol, opioid, or nicotine withdrawal)

Diazepam: anxiety and agitation associated with cannabis or opioid withdrawal

Bupropion (Zyban, Wellbutrin): dopamine reuptake inhibitor, antidepressant

(cravings and dysphoria in nicotine withdrawal)

Varenicline (Champix): nicotine receptor partial agonist

Various psychiatric medications (antidepressants, antipsychotics, mood stabilisers)

used off-label for psychological problems associated with withdrawal and postwithdrawal syndrome.

100

Medications for substance

dependence
Antagonists and allergenics:
Naltrexone:
Opioid receptor antagonist
Oral pills, long-lasting injections, or implants
Mildly effective at reducing alcohol cravings and reward

Blocks effects of opioids, but dangers associated with use in opioid

dependence

Disulfiram
Induces allergy to alcohol
Low effectiveness due to low compliance

101

Harm Reduction
Accepts that some will continue to use substances, but that associated
harms can be reduced.
Education about potential harms

Less harmful means of administration:

Needle & syringe programs
E-cigarettes, vapourisers
Encouraging alternative routes of administration to injecting
Pill testing
Agonist substitution for opioids
Overdose prevention:
Naloxone
Education

102

Prevention
Supply and opportunity reduction:
Effective in reducing tobacco use and dependence, some evidence for reducing
alcohol use

Increased taxes, minimum pricing

No-smoking areas

Restrictions on liquor licensing

Age restrictions

Prohibition, criminalisation:

Mixed evidence whether it reduces substance use: may depend on cultural

factors, ease of producing/transporting substance, etc.

Benefits vs. costs:

Produces other harms related to criminalisation (criminal activity, less quality control)

Emergence of replacement legal highs, some more dangerous than the illegal ones.

103

Prevention
Social and educational measures:
Restrictions on advertising
Public education campaigns
Regarding harms of use
Peer pressure resistance
Correcting false beliefs regarding use

Self esteem training

Family interventions: Delaying onset of use reduces

likelihood of dependence

Social change (employment opportunities, alternative

recreational activities)

104

Contact details
Joshua Garfield:
joshuag@turningpoint.org.au

(03) 9412 9957

Turning Point
54-62 Gertrude Street
Fitzroy, Victoria
3065