c83cli clinical psychology

C83CLI Clinical Psychology

Dr Mark Haselgrove

Mechanisms and Treatmentof Substance Addiction

Overview of the Lecture

Part A: Mechanisms of Substance addiction

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

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

(B) Mechanisms of Substance addiction.What effects of drugs motivate their use?

Addictive Phase

Initial Phase Early Late Methadone Post-Methadone

- 1 day to years- Intermittent use- Incentive motivation

-Daily use.- Periods of self-detox. 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

O-Brien, Ehrman & Ternes (1986)

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 heroinEnough cash to buy heroinPerson shooting up, being highSight of dealerMovie about junkiestalking 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)

Drug cues (CS)

Drug (US)

CR (At least) Two things should happen:

(1) Drug cues evoke CR(2) Effectiveness of the US diminishes when expected (Rescorla & Wagner, 1972)

(B) Mechanisms of Substance addiction.

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)

PREDICTION 1. CR to DRUG CUES


Better to demonstrate a similar effect in non-addicts - before dependency has been acquired

Glautier, Drummond & Remington (1994)

Perhaps addicts are just easier to condition to drug cues

- 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.

PREDICTION 1. CR to DRUG CUES


Siegel et al. (1983)

PREDICTION 2. Tolerance to Drug when it is cued (US effectiveness ↓)

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

Cue specific toleranceNon-specific tolerance (Habituation?)

Experiment run in 6 replications.Mortality DT>ST every time.

(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

Interesting, but...multiple shortcomings. E.g.:

(obviously) anecdotal. Non-controlled (he may have died if injected in bedroom)

Comparable reports by heroin overdose victims (Siegel, 1984)

(B) Treatment of Substance addiction.

If substance addiction = conditioning, then we can do something about this.

Theoretical Background

CS US

Session

CR

Chaudhri et al. (2008)

Stage 1:

CS+ → 0.2 ml of 10% AlcoholCS- → nothing

Stage 2:

CS+ → nothingCS- → nothing

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.


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.


McLellan et al (1986)

Conditioned withdrawal Former opiate addicts report withdrawal symptoms/craving Wikler (1948) upon exposure to stimuli associated with the drug → relapse

- 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)

Pilot study – Clients asked to “cook up” heroin, but then inject saline.

56 outpatient methodone treatment volunteers. Personality Q and structured interviews assessed addiction severity. Also measured co-morbid metal health problems (e.g. psychosis)


McLellan et al (1986) Cont...

Randomly assigned into 1 of 3 groups:

Experimental: CBT + Graduate Extinction + relaxationControl 1: CBT + RelaxationControl 2: Simple support/ counselling

Session = 30 min CBT, 15 min extinction, 15 min relax3 x week. 35 in total


McLellan et al (1986) Cont...

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 + ExtinctionSE-C: Supportive-Expressive Psychotherapy + Control activitiesDC-X: Drug counselling + ExtinctionDC-C: Drug counselling + Control activities

Extinction (each session):

3 x 5min drug videos3 x 5 drug audios3 x cocaine rituals

15 x 1 hour sessions over two weeks



O’Brian et al (1990)

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).

Data from Extinction groups...



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= Btw 0-10 units alcoholLevel 2= Btw 11-20 units alcoholLevel 3= Btw 21-30 units alcoholLevel 4= Btw 31-40 units alcoholLevel 5= Btw 41-50 units alcohol

on 3 daysconsecutive


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 ≈ 0.2-0.3Medium ≈ 0.5Large > 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)


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:


Stage 2:


Renewal Test:



Collins & Brandon (2002) Renewal to alcohol cues in humans

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:

Assumes participants have (already established) sight/smell of beer → beer association

Extinction: sight and smell of beer (but no opportunity to drink)Context = different rooms


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 contextas 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


Back to Chaudhri et al. (2008)

Extinction in multiple contexts attenuates renewal of cue-alcohol association

Stage 1:


Stage 2:


Renewal Test:


Implications for treatment

Cue exposure in a variety of locations(e.g. clinic, home, work, pub, etc…)

So what can be done about this?

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:

[email protected]

Room C9 (Psychology Building)

mailto:[email protected]

c83cli clinical psychology

Documents

drug use

presence of drug

nondrug reinforcement

absence of drug craving

drug naive group

effects of given dose

drug cues csdrug uscrat

cs cocaine