C83CLI Clinical Psychology
Dr Mark Haselgrove
Mechanisms and Treatment
of Substance Addiction
Overview of the Lecture
Part A: Mechanisms of Substance addiction
What effects of drugs motivate their use?
Conditioning analysis of substance addiction
(i) Drug cues elicit CRs in users and non-users
(ii) Tolerance is a diminution of the UR - evidence
Part B: Treatment of Substance addiction
Extinction of conditioning to alcohol cues
Cue Exposure
(i) Four Examples
(ii) Meta Analysis
(iii) Why doesn’t it work (so well) – the four Rs
Renewal
(i) Extinction of cue-alcohol learning in rats
(ii) Extinction of cue-alcohol learning in humans
What to do about all of this? Multi context cue-exposure therapy
(B) Mechanisms of Substance addiction.
What effects of drugs motivate their use?
O-Brien, Ehrman & Ternes (1986)
Addictive Phase
Initial Phase
- 1 day to
years
- Intermittent
use
- Incentive
motivation
Early
Late
Methadone
Post-Methadone
-Daily use.
- Periods of selfdetox. Again,
primarily
incentive
motivation
- Continuous use.
- Increasing
tolerance.
- Concerns about
withdrawal.
- Less importance
of incentive
motivation
-Little fear of
withdrawal.
-Drug use based
on desire for
euphoria.
- Non-drug
reinforcement can
be acquired
-Drug free.
- If relapse occurs
new period in
addictive phase
is brief. Then
rapid transition
to late addictive
phase
Phenomena to be explained:
Tolerance:
Adaptation to repeated exposure to drug. Effects of given dose of drug ↓.
Relative to first exposure
Dependence:
Often accompanying tolerance. Presence of drug required for normal
functioning. Absence of drug → craving, withdrawal symptoms
Relapse:
Resuming drug use after periods of non-use
(B) Mechanisms of Substance addiction.
What effects of drugs motivate their use?
O-Brien, Ehrman & Ternes (1986)
Examples of stimuli that elicit craving/withdrawal
symptoms in former heroin addicts:
Bag of heroin
Enough cash to buy heroin
Person shooting up, being high
Sight of dealer
Movie about junkies
talking about drugs
Also: anecdotal evidence that craving and relapse ↑ if
user is in environment where drug use was acquired
Conditioning (associative) Analysis (Siegel, 1983; 2005)
CR
Drug
cues
(CS)
(At least) Two things should happen:
Drug
(US)
(1) Drug cues evoke CR
(2) Effectiveness of the US diminishes
when expected (Rescorla & Wagner, 1972)
(B) Mechanisms of Substance addiction.
PREDICTION 1. CR to DRUG CUES
Foltin & Haney (2000) CR to drug cues in cocaine users
8 cocaine smokers (30-41 yrs old). Used drug 3-7 days a week (1-4 g smoked each binge)
Two different stimuli established CS+ → Cocaine, CS- → Placebo (e.g different smells/visual stimuli). CSs
presented for 2 min, then drug (or placebo) smoked (blindfolded & behind a screen)
Study lasted 15 days, repeated training (CS+, CS-) trials, and intermixed test days.
No control group though
(thus don’t know if the effect
is specific to addicts)
But Ehrman et al (1992) showed
CR effects specific to cocaine users.
No effect in drug naive group.
Monti, Rohsenow et al (1993).
alcohol abusers urge to drink,
salivation to a favourite drink (cf’d
to H2O was unchanged despite a
month of detox)
(B) Mechanisms of Substance addiction.
PREDICTION 1. CR to DRUG CUES
Perhaps addicts are just easier to condition to drug cues
Better to demonstrate a similar effect in non-addicts - before dependency has been acquired
Glautier, Drummond & Remington (1994)
- 12 male volunteers – none with a history of drinking problems
- Two colour/flavour compounds (red peppermint/ blue angostura) mixed with drinks
CS+ contained alcohol, CS- did not.
- Each day, for 8 days, look at then sip either the CS+ or CS-. Then consume whole drink in 10 min.
(B) Mechanisms of Substance addiction.
PREDICTION 2. Tolerance to Drug when it is cued (US effectiveness ↓)
Siegel et al. (1983)
Acquisition of a cue-specific tolerance (and overdose) in rats
Three groups of rats given following training:
ST
IV Heroin (up to 8mg /kg) in Room A. IV Dextrose in Room B
DT
IV Dextrose in Room A. IV Heroin (up to 8mg /kg)in Room B
Control Dextrose in Room A and Room B
Then, a test: All groups given 15mg/kg Heroin in ROOM A
Experiment run in 6 replications.
Mortality DT>ST every time.
Cue specific tolerance
Non-specific tolerance (Habituation?)
(B) Mechanisms of Substance addiction.
PREDICTION 2. Tolerance to Drug when it is cued (US effectiveness ↓)
Siegel & Ellsworth (1986)
Case study of cue-dependent tolerance
& overdose in human.
Pancreatic cancer patient. Attended to at home (by son N. E.).
4 x morphine injections/day for 4 weeks
Comparable reports by heroin overdose victims (Siegel, 1984)
Interesting, but...multiple shortcomings. E.g.:
(obviously) anecdotal.
Non-controlled
(he may have died if injected in bedroom)
(B) Treatment of Substance addiction.
Theoretical Background
If substance addiction = conditioning, then we can do something about this.
CR
CS
US
Chaudhri et al. (2008)
Stage 1:
CS+ → 0.2 ml of 10% Alcohol
CS- → nothing
Stage 2:
CS+ → nothing
CS- → nothing
Session
Presentation of drug associated cues in the absence of the drug, should weaken CR
(B) Treatment of Substance addiction.
Cue exposure Therapy
Repeated presentations of drug associated cues (CSs)
e.g. sight, smell of alcohol/cigarettes
IN THE ABSENCE
OF THE DRUG (US)
Raw & Russell (1980)
33 Heavy smokers (≈35 cigs/day) 20 Male, 29 female.
Assigned to 1 of 2 groups and received 3 weeks of treatment. Each session 45 min/day:
Simple support:
Record keeping, support, encouragement and praise from
therapist for abstinence. ss told to avoid smoking cues (e.g.
smoking area on bus)
Cue exposure:
As above, but ss encouraged to confront cues. In sessions, client
asked to light up and hold cig (not smoke) also drink coffee.
Therapist smoked, and offered cigs.
(B) Treatment of Substance addiction.
Cue exposure Therapy
Raw & Russell (1980) Cont...
- Simple support and cue exposure
reduced cig consumption
- Cue exposure no better than support
- Neither treatment prevented relapse
- R&R suggest failure of both treatments → Very heavy smokers ( twice the then national average)
- Perhaps CS-US association particularly strong in this sample – 3 weeks of extinction not enough to
counter this?
- This absence of effect replicated (Niaura etal , 1999). Not all addictions equally suited to cue
exposure.
(B) Treatment of Substance addiction.
Cue exposure Therapy
McLellan et al (1986)
Conditioned withdrawal
Wikler (1948)
Former opiate addicts report withdrawal symptoms/craving
upon exposure to stimuli associated with the drug → relapse
Pilot study – Clients asked to “cook up” heroin, but then inject saline.
- At first, clients reported injecting was pleasurable
- After repeated injections, it became aversive (elicited withdrawal symptoms). Drop out ↑
Graduated Extinction –
Hierarchy of CS extinguished in turn, building up a tolerance to “cooking up”, and injecting.
Sessions also followed with relaxation training (a la systematic desensitization; Wolpe, 1958)
(B) Treatment of Substance addiction.
Cue exposure Therapy
McLellan et al (1986) Cont...
56 outpatient methodone treatment volunteers. Personality Q and structured interviews
assessed addiction severity. Also measured co-morbid metal health problems (e.g.
psychosis)
Randomly assigned into 1 of 3 groups:
Experimental:
CBT + Graduate Extinction + relaxation
Control 1:
CBT + Relaxation
Control 2:
Simple support/ counselling
Session = 30 min CBT, 15 min extinction, 15 min relax
3 x week. 35 in total
(B) Treatment of Substance addiction.
Cue exposure Therapy
McLellan et al (1986) Cont...
(B) Treatment of Substance addiction.
Cue exposure Therapy
O’Brian et al (1990)
30 drug-free former cocaine addicts (23-53 ys old). ≈3 years of drug use. Clean for 7-10 days
Baseline assessment:
Responsively to cocaine related stimuli.
Physiological measures (temp, HR, GSR).
Self report Q (subjective high, craving, withdrawal etc)
Randomly assigned into 1 of 4 groups:
SE-X:
Supportive-Expressive Psychotherapy + Extinction
SE-C:
Supportive-Expressive Psychotherapy + Control activities
DC-X:
Drug counselling + Extinction
DC-C:
Drug counselling + Control activities
Extinction (each session):
3 x 5min drug videos
3 x 5 drug audios
3 x cocaine rituals
15 x 1 hour sessions over
two weeks
(B) Treatment of Substance addiction.
Cue exposure Therapy
O’Brian et al (1990)
Data from Extinction groups...
Little data presented from control groups. Qualitative reports:
- Much lower drop out rate in extinction groups (8 week program, ex grps lasted 6.5 and 7 weeks,
controls, 1 week & 3.5 weeks).
- Urine metabolites revealed ex groups had more weeks with clean samples than control groups (no
stats here though).
(B) Treatment of Substance addiction.
Cue exposure Therapy
Drummond & Glautier (1994)
108 male patients referred from hospital alcohol clinic. 63 dropped because of
mental/physical health complications, or insufficiently severe alcohol dependence.
Final N = 45
Clients assigned into 1 of 2 groups:
CE (Cue exposure):
Exposed to alcohol stimuli
(handling drink, smell) for 40 min/day
10 consecutive weekdays.
1st 5 days - ↑ salience alcohol drink
2nd 5 days ↓ salience drink)
RC (Relaxation control):
Progressive relaxation training
in replacement of CE
Level 1=
Level 2=
Level 3=
Level 4=
Level 5=
Btw 0-10 units alcohol
Btw 11-20 units alcohol
Btw 21-30 units alcohol
Btw 31-40 units alcohol
Btw 41-50 units alcohol
on 3 days
consecutive
(B) Treatment of Substance addiction.
Cue exposure Therapy
Conklin & Tiffany (2002) – Conducted a meta analysis
18 non-case study cue exposure treatment studies
9 met criteria for meta analysis:
(i) The study included a control (or comparison treatment) group
(ii) Post treatment follow up was included.
+ = CE > cntrl
-= CE < cntrl
Cohen (1992):
Small ≈ 0.2-0.3
Medium ≈ 0.5
Large > 0.8
Overall effect size
d = 0.08, n/s
Q(9) = 16.07, p=.04
(indicates the effect size
was not consistent
across studies)
(B) Treatment of Substance addiction.
Cue exposure Therapy
Why is cue exposure so unreliable? Extinction works so well!
The Four Rs (Bouton et al, in Haselgrove & Hogarth, 2012)
(B) Treatment of Substance addiction.
Renewal
Chaudhri et al. (2008)
Stage 1:
CS+ → 0.2 ml of 10% Alcohol
CS- → nothing
Stage 2:
Renewal Test:
CS+ → nothing
CS- → nothing
CS+ → nothing
CS- → nothing
(B) Treatment of Substance addiction.
Renewal
Collins & Brandon (2002) Renewal to alcohol cues in humans
Assumes participants have (already established) sight/smell of beer → beer association
293 students agreed to volunteer in a beer drinking study. 112 met criteria after screening
(Criteria = drank at least 1 or 2 times a week, and sessions > 3 to 4 cans of beer).
Final N (after drop outs) = 78. Assigned to 1 of three groups:
Extinction: sight and smell of beer (but no opportunity to drink)
Context = different rooms
(B) Treatment of Substance addiction.
Renewal
Collins & Brandon (2002) Renewal to alcohol cues in humans
Testing in a different context:
(1) More drooling
(2) Greater urge to drink
Implications for treatment:
Cue exposure in same context
as addiction acquired
Less successful attempts at replication:
Stasiewicz et al. (2007) [alcoholics]; MacKillop & Lisman (2008)
- Important to be sure the contexts are v different otherwise renewal will be weakened
(B) Treatment of Substance addiction.
Renewal
So what can be done about this?
Back to Chaudhri et al. (2008)
Extinction in multiple contexts attenuates
renewal of cue-alcohol association
Stage 1:
CS+ → 0.2 ml of 10% Alcohol
CS- → nothing
Stage 2:
Renewal Test:
CS+ → nothing
CS- → nothing
CS+ → nothing
CS- → nothing
Implications for treatment
Cue exposure in a variety of locations
(e.g. clinic, home, work, pub, etc…)
Thank you...
(1) Pdfs on moodle and my webpage.
(2) My book (Ch 4: vulnerabilities to dependence)
(Ch 5: Relapse, extinction & renewal)
(3) Questions via moodle, or:
Mark.Haselgrove@nottingham.ac.uk
Room C9 (Psychology Building)