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INTRODUCTION TO ADDICTION
Benjamin R. Nordstrom, M.D., Ph.D.
Assistant Professor of Psychiatry
Geisel School of Medicine at Dartmouth
Director of Addiction Services
Dartmouth Hitchcock Medical Center
Learning Objectives
• Relate the disease model of addiction
• Describe the three common variants of relapse
• Describe how operant and classical conditioning relate to
addiction
• Understand how buprenorphine and methadone affect
operant conditioning and treat addiction
Drug use is common…
• In 2011, 22.5 million people (8.7% of the U.S.
population) were current users of illicit drugs.
(SAMHSA 2012)
• 8 % of the population met criteria for substance
abuse or dependence (ibid)
• 3% of the population will meet criteria for drug
abuse or dependence at some point in their lives
(Grant 1996)
Drug use is common- cont’d
• Painkillers are second only to cannabis in number of
people meeting abuse or dependence criteria (1.8 million
vs. 4.2 million) (SAMHSA 2012)
• Between 2004 and 2011, the number with pain reliever
dependence or abuse increased from 1.4 million to 1.8
million (ibid)
Past Month Use of Selected Illicit Drugs among Persons Aged
12 or Older: 2002-2011 (SAMHSA 2012)
Past Month Nonmedical Use of Types of Psychotherapeutic
Drugs among Persons Aged 12 or Older: 2002-2011
(SAMHSA 2012)
Past Year Initiates of Specific Illicit Drugs among Persons Aged
12 or Older: 2011 (SAMHSA 2012)
Other Stats
• U.S. has 4.6 % of the world’s population yet consumes
80% worlds opioids (Pain Physician 2010: 13:401-435
• The average mg/person use of opioids has increased
399% from 1997 to 2007 (ONDCP 2011)
• Opioids account for 75% of prescription drugs being
abused (ibid)
• Retail pharmacies filled nearly 50% more Rxs for opioids
in 2009 compared to 2000 (FDA via BDAS 2012)
Source Where Pain Relievers Were Obtained for Most Recent
Nonmedical Use among Past Year Users Aged 12 or Older: 2010-2011
(SAMHSA 2012)
(NH BDAS 2012)
(NH BDAS 2012)
(NH BDAS 2012)
(NSDUH 2008-2009 via NHBDAS 2012)
(NH BDAS 2012)
Addiction
• Drug use starts out because it is
pleasurable and/or helps avoid pain
• Drug use pursued in such a way that
negative consequences follow
• Drug use persists in the face of negative
consequences and the desire to quit (i.e.
after it no longer “makes sense”)
DSM IV: Substance Abuse
Maladaptive pattern with significant impairment/distress
For 12 months, at least 1 of the following criteria:
Failure to fulfill major role obligations
Use in physically hazardous situations
Legal problems
Recurrent social/interpersonal problems
Never met Dependence Criteria
DSM IV: Substance Dependence
Maladaptive pattern of drug use for >12 months
Must satisfy 3 of the following 7 criteria:
• Tolerance
• Withdrawal
• More use than intended (loss of control)
• Unsuccessful efforts to quit
• Significant time spent in procurement, use, recovery
• Functional impairment
(social, occupational, recreational)
• Continued use in the face of adverse health effects
Classical Conditioning
• Also called “associative learning”
• Pavlov’s dogs
• Conditioned stimulus + Unconditioned Stimulus
 Unconditioned Response
• Conditioned stimulus  Conditioned Response
• Allows previously neutral stimuli to be imbued
with hedonic salience
Operant Conditioning
• Reinforcement increases the frequency of a
behavior
• Positive reinforcement
• the behavior makes a good feeling start
• Negative reinforcement
• the behavior makes a bad feeling stop
Natural Rewards
• Eating
• Drinking
• Sex
• Certain behaviors
• Nurturing
• Aggression
Cycle of Addiction
Drug Euphoria
+
Brain Reward
Neuroadaptations
Drug Craving
But not all users become addicted…
• 17-22% (snorting vs. smoked) of people who try
cocaine will go on to develop a dependence
syndrome to it
• 23% of people who try heroin will become
addicted.
• 9-10% of people who try cannabis will become
addicted to it.
• 15% of people who try alcohol will become
alcoholics,
• 32% of people who try cigarettes will become
nicotine dependent. (Anthony, Warner et al.
1994)
Routes of Administration
Oral
Intranasal
Intravenous
Intrapulmonary
Intrapulmonary
By-passes the
venous system
(Science 278:45-47, 1997)
Disease Model of Addiction
• It has identifiable symptoms.
• It has a predictable course.
• It has a treatment that is as successful as that of
many chronic diseases (e.g diabetes,
hypertension, asthma).
• All addictive substances act an one area of the
brain (the ventrotegmental tract or reward
system)
Disease model cont’d
• Prolonged drug or alcohol use causes
pervasive changes in brain function that
persist long after the drug taking stops.
• The addicted brain is distinctly different from
the non-addicted brain as manifested in
brain metabolic activity, receptor availability,
gene expression and responsiveness to
environmental cues.
Relapse
• Cue-induced relapse
• Stress-induced relapse
• Drug-induced relapse
Cue induced relapse
• Train a rat to self-administer drugs in a
cage with a checkered floor
• Extinguish the response
• Reintroduce the rat to a checkered floor
and it again attempts to self-administer
drug
• Human analogue: “People, places and
things.”
Stress-induced relapse
• Train a rat to self-administer drugs
• Extinguish the response
• Give the rat a powerful foot shock and it will
attempt to self-administer drug
• Human analogue: “HALT”
• (Hungry, Angry, Lonely, Tired)
Drug-induced Relapse
• Train a rat to self-administer drug
• Extinguish the response
• Give it drug unexpectedly and it will attempt
to self-administer
• Human analogue, “One is too many, and a
thousand isn’t enough.”
Opioid addiction
• Tolerance develops quickly
• Use gets perpetuated by….
• Positive reinforcement
• Get euphoria (high)
• Negative reinforcement
• Get withdrawal when wears off
• Withdrawal is pretty unpleasant
Methadone
 Works on the same receptor (mu opioid receptors) as heroin and
other abused opioids
 Can use it to taper people down
 Build a “chemical staircase” for them to walk down
 Can use it to maintain people as well
 Put on same dose of methadone as heroin
 Stops withdrawal
 Ratchet up dose to way past how much heroin they used
 Price it out of reach
 Stops positive and negative reinforcement
Buprenorphine
Pharmacodynamics
• High affinity for the mu opioid receptor
• Competes with other opioids and blocks their effects
• Slow dissociation from the mu opioid receptor
• Prolonged therapeutic effect for opioid dependence
treatment
• Long half life (20-44 hours)
• Prevents negative reinforcement
Efficacy: Full Agonist (Methadone) Partial Agonist
(Buprenorphine), Antagonist (Naloxone)
100
Full Agonist
(Methadone)
90
80
70
%
Efficacy
60
Partial Agonist
(Buprenorphine)
50
40
30
20
Antagonist
(Naloxone)
10
0
-10
-9
-8
-7
Log Dose of Opioid
-6
-5
-4
Mu opioid partial agonist
• Ceiling effect imparts safety
• Less respiratory depression
• Less risk of overdose
• Less physical dependence capacity
Zubieta et al., 2000
Buprenorphine Maintenance/Detoxification
• 52-week study, week 1 inpatient
• Take home doses potentially allowed after 6 months
• Outcome measures included
- Treatment retention
- Urine toxicology: three times per week, supervised
- ASI scores
Remaining in treatment (nr)
Buprenorphine Maintenance/Detoxification: Retention
20
15
10
Detox/placebo
5
Buprenorphine
0
0
50
100
150
200
250
Treatment duration (days)
300
350
(Kakko et al., 2003)
Buprenorphine Detox vs. Maintenance:
Mortality
Mortality
Detox/Placebo
Buprenorphine
Cox regression
4/20 (20%)
0/20 (0%)
c2=5.9; p=0.015
(Kakko et al., 2003)
Buprenorphine Maintenance/Detoxification
Kakko 2003 demonstrates:
• Efficacy of maintenance treatment
• Poor outcomes associated with detoxification (despite
extensive psychosocial treatment after inpatient
detoxification)
Buprenorphine, Methadone, LAAM:
Treatment Retention
Percent Retained
100
80
73% Hi Meth (100mg/d)
60
58% Bup (32mg TIW)
40
53% LAAM (equiv 100mg/d)
20
20% Lo Meth (20mg/d)
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Study Week
Adapted from Johnson, et al., 2000
Buprenorphine, Methadone, LAAM:
Opioid Urine Results
100
Mean % Negative
80
LAAM (equiv 100mg/d)
60
Bup (32mg TIW)
Hi Meth (100mg/d)
40
Lo Meth (20mg/d)
20
0
1
3
5
7
9
11
Study Week
13
15
17
Adapted from Johnson, et al., 2000
What is right for whom?
Methadone
Buprenorphine
• Chronic pain
• Jobs/ travel
• Unable to manage
• Live far from a methadone
medication or infrequent
visits
• Need intense, “in-house”
psychosocial interventions
• Have failed
buprenorphine
program
• No confounding issues
THANKS!!!!
• [email protected]
• 603-653-1860