Lecture Addiction

Addiction:
a treatable brain disease

Dr. Arnt Schellekens

Radboud umc Donders/Afdeling Psychiatrie,
Nijmegen Institute for Scientist Practitioners
in Addiction

september 2014
 Content
• What are addictive substances
(and other relevant concepts)?

• Addiction a brain disease?

• Addiction a treatable brain disease!

• Psychiatric co-morbidity…

• New treatment modalities

• Conclusions

• Perceptions about addiction.

 Learning Objectives

• Key concepts
• Neurobiology
• Treatment
• Motivational interviewing
• New treatments in research
What are addictive substances?
 What are addictive substances?

• Substances with rewarding effects, i.e.

substances that make you feel good
(EUPHORIA)

• Substances that make people think

about using all the time
(CRAVING)

• Substances that people cannot stop “Het water loopt in je mond”

using
(LOSS OF CONTROL)
Examples of addictive
substances

SEDDATIVES Alcohol, opiates,

benzodiazepines
barbiturates

STIMULANTS Caffeine, nicotinE,

amfetamines
cocaine, XTC

PSYCHEDELICS Cannabis, LSD,

psylocybine,
mescaline
 Important concepts: Craving,
Intoxication, Tolerance, Withdrawal
• Intoxication
psychological and physical consequences due to excessive use of
psychoactive substances, that disappear when use is terminated

• Tolerance
Physiological adaptation, whereby incrasing amounts are needed for similar
effects (commonly observed with medication)

• Withdrawal
Physiological effects that appear when a commonly used substance is no
longer used (or a a lower dose). Is also commonly observed with medication

• Craving
Strong desire/urge to use substances (not in DSM-IV, but in DSM-5 and ICD-
10)

Loss of Control Dependence

 Important concepts: Abuse,
Dependence, Addiction
• Abuse
Use of substances that is associated with psychological or scietal
problems (in functioning)

• Dependence
Uncontrolled use of substances, due to craving for the substance
and/or withdrawal symptoms, resulting in physical, psychological
and/or social problems

• Addiction
Dependence with uncontrolled use of substances that is hard to quit,
due to automatic tendencies/procesess, and requires professional
help
 DSM-IV: Substance Abuse

Maladaptive pattern of substance use, leading to clinically

significant impairment or distress. Manifested by one (or
more) of the following, occurring at any time in the same 12
month period:

1. Recurrent substance use resulting in a failure to fulfill

major role obligations at work, school, or home
2. Recurrent substance use in situations in which it is
physically hazardous
3. Recurrent substance-related legal problems
4. Continued substance use despite having persistent or
recurrent social or interpersonal problems caused or
exacerbated by the effects of the substance
 DSM-IV: Substance Dependence

Maladaptive pattern of substance use, leading to clinically

significant impairment or distress. Manifested by three (or
more) of the following, occurring at any time in the same 12
month period:

1. Tolerance
2. Withdrawal
3. Substance taken in larger amounts or longer period
4. Persistent desire or unsuccessful efforts to cut down use
5. Great deal of time is spend related to substance, use
6. Interference with social, occupational, or recreational
functioning
7. Continued use despite knowledge of negative
cpnsequences
 DSM-IV: Substance Dependence

Maladaptive pattern of substance use, leading to clinically

significant impairment or distress. Manifested by three (or
Three levels:
• Physiological
more) of the following, occurring at any time in the same 12
dependence
• Loss
month period:
of control
• Interference with functioning
1. Tolerance
2. Withdrawal What about craving!?!
3. Substance taken in larger
Isn’t that amounts
the core or longer period
of addiction???
4. Persistent desire or unsuccessful efforts to cut down use
5. Great deal of time is spend related to substance, use
6. Interference with social, occupational, or recreational
functioning
7. Continued use despite knowledge of negative
cpnsequences
 Learning Objectives

• Key concepts
• Neurobiology
• Treatment
• Motivational interviewing
• New treatments in research
 A Brain disease

• Heritability

• Brain changes
Heritability (%) Heritability of alcohol dependence

Bienvenu et al. 2011, Psychological Medicine

 Heritability per drug
Heritability

Addictive potential
 Heritability of smoking

100%

80%

60%
omgevingsfactoren
40% erfelijkheid

20%

0%
begin van verslaving
gebruik
 Gene Environment Interaction
Risk Alcohol dpeendence

Risk Gene

No Risk Gene

Exposure childhood trauma

Schellekens et al. 2013, Addiction Biology

Gene Environment Interaction

Zwaluw et al. 2011, Mol. Psych.

 A Brain disease

• Heritability

• Brain changes
 Dopamine and reward

Dopamine

Stahl 2000
Het natuurlijke
beloningssysteem
Het natuurlijke
beloningssysteem
 “reward pathway”

cannabis GABA amphetamine

alcohol
DA
opioid

cocaine
ACh

nicotine PCP

alcohol
5HT
Glu
hallucinogen
(Stahl 2000)
Decreased DA Binding
in Corpus Striatum in
Alcohol and Drug
Addicts after
Prolonged Abstinence

Reward Deficiency?
Cocaine self administration in monkeys
Cocaine self administration in monkeys
Cocaine self administration in monkeys
Effect of social environment
Prefrontal Cortex and ACC Under-Activity
after Sustained Abstinence
 I-RISA Model of Addiction
Volkow (2004)

Control Control

Salience Drive STOP Salience Drive GO

Memory Memory

Non-Addicted Brain Addicted Brain

 Learning Objectives

• Key concepts
• Neurobiology
• Treatment
• Motivational interviewing
• New treatments in research
 Addiction =
a treatable brain disease!

Psychosocial treatment options

 Psychosocial interventions

• Motivational interviewing
• Cognitive Behavioral Therapy
– Social skills training
– Self-control training
– Cue-exposure
• Community Reinforcement Approach
• Self-help groups
• 12-steps (Minnesota model)
• Internet treatment
Motivation cycle
(Prochaska & DiClemente)
Motivation cycle
(Prochaska & DiClemente)
 Community Reinforcement
Approach (CRA)
Treatment method aiming at abstinence by:
• Diminishing positive reinforcement of
substance use
• Enhancing positive reinforcement of
abstinence

CRA integrates a variety of effective

interventions
 Interventies in CRA
Aiming at:
• Improing the social network
• Increasing compliance
• Increasing motivation
• Increasing perspective
(including skills training, hobbies, work)
 Contingency Management
(CM)
• Positive reinforcement of desired
behavior (as outlined in the treatment
plan)
• E.g.: negative urine tests
• Incentive: vouchers
• Meta-analyses: large effect-sizes!
 Internet treatment

• E.g. alcoholdebaas.nl
• Distinct target population
• Effective and anonymous
• Health insurance coverage?
 Addiction:
a treatable brain disease
Pharmacological interventions
 “reward pathway”

cannabis GABA amphetamine

alcohol
DA
opioid

cocaine
ACh

nicotine PCP

alcohol
5HT
Glu
hallucinogen
(Stahl 2000)
 Alcohol Detox

Vitamine B1 (thiamine >=100mg im 2-3days

Benzo tapering
 Alcohol Dependence

Acamprosate

Disulfiram

Topiramate
Naltrexone

Ondansetron
Naltrexon Pharmacogenetica
Oslin et al, Neuropsychopharmacology, 2003

Δ = 30%
Δ = 15%

A/G, G/G =32%

AA = 68%
 Benzo Detox

1. Benzo substitution
2. Benzo tapering
Medicatie Cannabisafhankelijkheid

No effective medications available

Hart (2005) Drug and Alcohol Dependence

Medication Cocaine dependence

No effective medications available

Hart (2005) Drug and Alcohol Dependence

 Medication Heroin dependence

• Detox: methadone, buprenorphine, rapid

detox, cold turkey
• Relapse prevention: naltrexone,
buprenorphine
• Substitution: MMT, heroine

Hart (2005) Drug and Alcohol Dependence

 Addiction
a treatable brain disease

Psychiatric Comorbidity
Anxiety and relapse

Anxiety
disorders

(Schellekens et al. 2014)

Anxiety and ERN

(Schellekens et al. 2012)

Reward processing

(Schellekens et al. in preparation)

 Treatment of Psychiatric Co-
Morbidity
• Assessment and treatment after a period of prolonged
abstinence or stabilisation

• Medication ± equally effective as in non-addicted

patients

• Succesful treatment of psychiatric comorbidity does not

(positively) affect the addiction

• Integrated treatment is required

 Conclusions
• Addiction is a brain disease

• The core symptom of addiction is craving with loss of

control

• Addiction is often unrecognized and Addicted patients

enter treatment often in late stage

• Addiction is a treatable condition

• Psychiatric comorbidity is the rule rather than an

exception
 Learning Objectives

• Key concepts
• Neurobiology
• Treatment
• Motivational interviewing
• New treatments in research
New treatment methods
• Suboxone • TMS

• Ibogaine • Baclofen

• Flumazenil • Mindfulness

• CBM

• OPRM1
 Pharmacogenetics: Naltrexone

(Oslin et al. Neuropsychopharmacology, 2003)

Thanks to collaborators:
Prof. Dr. Barbara Franke
Prof. Dr. Robbert-Jan Verkes
Prof. Dr. Bart Ellenbroek
Prof. Dr. Jan buitelaar
Prof. Dr. Alexander Cools
Prof. Dr. Roshan Cools
Prof. Dr. Andre vd Ven
Prof. Dr. Marc Lewis
Dr. Martine Hoogman

Prof. Dr. Cor de Jong

Dr. Boukje Dijkstra
Drs. Maarten Belgers
Drs. Erik Paling
Drs. Toon v Oosteren
Drs. Rama Kamal
Drs. Harmen Beurmanjer

Dr. Shelly Iskandar

Dr. Astri Parawita Ayu
Dr. Rudi Wisaksana

Dr. Sumari
 Psychiatrienet.nl
• Opleidingen: MiAM,
Verslavingspsychiater
• Verenigingen: NVvP, VVGN
• NISPA
 Verslaving
een Behandelbare Hersenziekte

Neurobiologische Interventies
Hoe kijken we naar verslaafden?
Geschiedenis van Verslaving

Marlatt

Jellinek
Hoog Hullen
 Verslaving 1990-heden

Charles O’Brien

• Hersenziekte model: 1990-nu (CGT and medicatie)

 Verslaving 1990-heden

Modellen
1. Morele zwakte
2. Farmacologie
3. Persoonlijkheidsprobleem
4. Medische model Charles O’Brien

5. Multifactorieel: genetica en
hersenen

• Hersenziekte model: 1990-nu (CGT and medicatie)

 Aanwijzingen Hersenziekte

• Genetische kwetsbaarheid

• Betrokkenheid van het brein:

• Effect van medicatie
 Herkenning door screening
• Cage
– Cut down
– Annoyed by criticism
– Guilty about drinking
– Eye-opener

• AUDIT-C
– Hoe vaak drinkt u alcohol?
– Hoeveel drinkt u op een typische dag dat u alcohol
gebruikt?
– Hoe vaak drinkt u meer dan 6 glazen per
gelegenheid?
Wat is Verslaving?
 Verslaving is:

• Een chronische hersenziekte

• Met een destructieve leefstijl
• Voor de persoon en zijn omgeving
http://www.psychiatrienet.nl/ (p.96)
GHB