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Craving to quit: insights from

studies of mindfulness training

for alcohol, cocaine andnicotine dependence

Judson Brewer MD PhDMedical Director

Yale Therapeutic Neuroscience ClinicAssistant Professor

Department of PsychiatryYale University School of Medicine

www.ytnc.yale.edu


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For our consideration What is stress and how do we cope?

What is mindfulness? Does mindfulness help us with our addictions?

What do we know about neural mechanisms of

mindfulness? Mindlessness as a starting point

Our default mode?

How does the average meditators braindiffer from anyone elses?

How can neuroscience improve treatment ofstress and related disorders?


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Stress

Consequences of the failure to respondappropriately to emotional or physical

threats to the organism, whether actual

or imagined. (Selye 1956) [Ven. Sariputta:]"Now what, friends, is

the noble truth of stress? not getting

what is wanted is stressful... (MN 141)


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Stress and Addiction

Acute stress leads to increases in self-administration of drugs such as amphetamines(Bradley 1989), cocaine (Kalivas 1989), and alcohol (Nash1988)

Stress induces drug craving (Sinha 2005) andconsumption (De wit 2003)

Stressful life events are associated with nicotinedependence (Balk 2009)

Negative affect drives continuation of smoking(Markou 1998)


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Stress and Relapse

Stressful events, negative emotions andpsychological distress are frequently cited reasonsfor relapse to drug use among opiate and cocaine

addicts (Grant 1994, Lowman 1996, Marlatt 1985). Exposure to stressors increases relapse to

smoking (Swan 1998, Cohen 1990)

Lapses in smoking abstinence that are triggered by

stress progress more quickly to relapse (Shiffman1996)


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Sensory

Information

Changes

how we see

the world


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Sensory

Information

Changes

how we see

the world


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Sensory

Information


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Craving, not having, is the mother of a

reckless giving of oneself.

-Eric Hoffer


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Automated

Neutral Cue(get in your car)

Negative Cue(get yelled at by your

boss)

Positive Cue(have a good meal or

sex)

Negative Affect

(stressed out)

Positive Affect

(happy or relaxed)

AVOIDANCE

OF CUES

SUBSTITUTEBEHAVIORS

CRAVINGre

in

Zinser 1992, Piasecki 1997, Carter 1999, Lazev 1999, Cox 2001, Robinson 2003, Bevins 2004, Baker 2004, Coo

2004, Olausson 2004, Shiffman 2004, Carter 2008, Perkins 2010

SMOKE

Reinforcement of

Associative Memory/Habit

(smoking makes you feel

better)

Maintain or Increase

Positive Affect/Decrease

Negative Affect


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I can't get no satisfactionI can't get no satisfaction

'Cause I try and I try and I try and I try

I can't get no, I can't getno

-Mick Jaggar


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Self-control: competing systems Affective (self-referential?)/hot processing

involves self-referential valuation, is automatic andunplanned, and influences behavior through impulses (Weber2004, Kable 2007).

fronto-striatal-limbic loop, including the orbitofrontal cortex,

ventromedial prefrontal cortex (vmPFC), posterior cingulate

cortex (PCC), and ventral striatum (McClure 2004; Hare 2009; Kober2010)

Deliberative/cold processing

effortful, influences behavior through rules of logic

and involved in inhibitory control (Weber 2004; McClure 2004;Ochsner 2005, Knoch 2007; Hare 2009)

dorsolateral prefrontal cortex (dlPFC), and posterior

parietal cortex etc (McClure 2004; Hare 2009; Kober 2010; Steinbeis2012)


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HOT COLD

How to improve the balance

between cold and hot processing?


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There is no end of craving. Hencecontentment alone is the best way

to happiness.

-Sivananda Saraswati


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Overview of Mindfulness

Two Component Definition:

1) Self-regulation ofattention so that it is

maintained on immediate experience, therebyallowing for increased recognition of mentalevents in the present moment.

2) Adopting a particular orientation toward ones

experiences in the present moment,characterized by curiosity, openness, andacceptance.

Bishop 2004


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Sensory

Information


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Trigger


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Applied mindfulness: RAIN

RECOGNIZEOh thats a craving

ACCEPT/ALLOW

See if you are resisting the experience

INVESTIGATE

whats happening in my body right now?

NOTE

Label or mentally note the body

sensations from moment to moment


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Pilot Study of MT for Addictions

Mindfulness Based Relapse Prevention vs. CBTfor alcohol and/or cocaine dependence

randomized controlled trial

No previous trials of MT as primary treatment

No previous trials of MT vs. active controlgroup

Is it well-tolerated? (yes)

Does it stack up to gold standard treatment (yes)

Does it change psychological and physiologicalresponses to stress? (yes)

Brewer et al 2009


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Does mindfulness

training work forsmoking cessation?


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Nicotine dependence is

difficult to treat

70% of smokers report wanting

to quit (CDC, 2002)

5% of individuals achieve

abstinence annually (CDC, 2002)

High relapse rates (>70%)


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Mindfulness Training for Smoking

1 month outpatient training (twice weekly):

Emphasis on awareness, acceptance of andworking with craving/wanting

Setting aspirations: work toward a quit date at theend of week two

Learn relationship between craving and behavior Body scan, loving-kindness meditations (formal)

RAIN (informal)

Reinforcing resolve: work skillfully with cravings for

the remaining two weeks Interaction of thoughts with body sensations

Breath awareness meditation (formal)

Noting craving, realigning with aspirations,

moving forward using RAIN etc. (informal)


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Allocated to FFS (n=47)

Started Treatment (n=39)

Randomized but did not complete baseline

assessments or start treatment (n=8)

Completed Treatment (n=32)*

Allocated to MT (n=41)

Started Treatment (n=33)

Randomized but did not complete baseline

assessments or start treatment (n=8)

Completed Treatment (n=29)*

Randomized (n=88)

*Attended 6 out of 8 sessions

**Excluded from all analyses due to VA regulations

***Mistakenly force randomized to MT

Screened by Phone (n=757)

Assessed for Eligibility (n=134)

Did not meet inclusion/exclusion criteria (n=459)Eligible by phone screen but not interested

or lost to follow-up (n=212)

Completed 6 week follow-up interview (n=33) (87%)

Completed 12 week follow-up interview (n= 32) (84%)





Dropped out before randomization (n=12)

Did not meet inclusion/exclusion criteria (n=21)

Force randomized to MT*** (n=3)

Included in Analysis (n=41)Included in Analysis (n=46)

Excluded from analysis (**incarcerated, n=1)

Brewer et al 2011

G


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0

2

4

6

8

10

12

14

16

18

20

1 2 3 4 5

FFS

MTS

Average

Cigare

ttes

/day

Treatment week

0 1 2 3 4

Brewer et al 2011

Group*Time

F=11.11, p=.001

Greater reduction in smoking with

MT vs. Freedom from Smoking


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0

5

10

15

20

25

30

35

40

End of Treatment 17 week follow-up

Po

intPreva

lence

Abs

tinence

(%)

MT FFS

Greater smoking abstinence with

MT vs. Freedom from Smoking

*p = .063

**p = .012

*

**

Brewer et al 2011


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What about craving? Craving intensity predicts smoking relapse risk in both

adults and adolescents (Shiffman 1997, Bagot 1997) Every additional point on the Questionnaire on Smoking

Urges (QSU) increased risk of lapse in adults by 10%

relapse within 1 week of cessation (Killen & Fortmann 1997)

> 32% of those with high craving scores

< 15% of those with low craving scores

In a study of 324 treatment-seeking smokers: (Ferguson2006)

For each 1 SD increase in craving score on targetquit date, daily risk of lapsing rose 43%

For each 1 SD increase in the average craving

experienced during a given day, risk of lapsing the

following day rose 65%


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Working hypothesis

Hypothesis: MT works by decouplingcraving and behavior (e.g. smoking)

Prediction: should see dissociation

between craving and smoking

BEFORE they both subside

i.e. should still have some craving,

but it is not coupled to smoking


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What about craving? Craving intensity predicts smoking relapse risk in both

adults and adolescents (Shiffman 1997, Bagot 1997) Every additional point on the Questionnaire on Smoking

Urges (QSU) increased risk of lapse in adults by 10%

relapse within 1 week of cessation (Killen & Fortmann 1997)

> 32% of those with high craving scores < 15% of those with low craving scores

In a study of 324 treatment-seeking smokers: (Ferguson2006)

For each 1 SD increase in craving score on targetquit date, daily risk of lapsing rose 43%

For each 1 SD increase in the average craving

experienced during a given day, risk of lapsing the

following day rose 65%


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Working hypothesis

Hypothesis: MT works by decouplingcraving and behavior (e.g. smoking)

Prediction: should see dissociation


BEFORE they both subside

i.e. should still have some craving,

but it is not coupled to smoking

C i d i tt b


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Craving and cigarette use become

dissociated during treatmentBaseline(Week 0)

End ofTreatment

(Week 4)

6-WeekFollow-Up

3-MonthFollow-Up

4-MonthFollow-Up

Craving (QSU)

X

Cigarette Use

r = 0.582

p < 0.001

N = 32

r = 0.126

p = 0.491

N=32

r = 0.474

p = 0.020

N = 25

r = 0.788

p < 0.00001

N=28

r = 0.768

p < 0.00001

N=29

p = .04

Predictor of Smoking r R2 p Effect size

Overall ModelBaseline Craving

Baseline Cigarette Use

End of Treatment Craving

Informal practice (days/wk)

Craving*Informal (days/wk)

0.735 0.5400.266

-0.053

0.208

-1.522

0.515

0.0010.591

0.53

0.652


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MTpracticemodifies relationship


Variable r r2 p df bb

(standardi

zed)

p

Baseline QSU 0.582 0.339 < 0.00011,

313.41 0.58 < 0.0001

Week 4 QSU 0.126 0.016 0.491

2,

31 0.41 0.13 0.491QSU+

Formal(days/week)

0.561 0.315 0.0042,

31

0.47,

-1.33

0.14,

-0.55

0.358,

0.001

QSU+

Informal(days/week)

0.484 0.234 0.0212,

31

0.35,

-0.99

0.11,

-0.47

0.516,

0.008

QSU+

Formal(total

minutes)

0.482 0.232 0.0222,

31

0.33,

-0.009

0.10,

-0.47

0.533,

0.008

QSU+

Informal(total times)

0.566 0.320 0.0042,

31

0.56,

-0.03

0.17,

-0.55

0.273,

0.001


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Moderation in a single slide(as taught by a psychiatrist)

Independent Variable (X)psychotherapy

Dependent Variable (Y)depression

Moderator Variable (M)gender

A moderator (M) is a variable that alters the direction

or strength of the relation between a predictor and

outcome (Frazier 2004)

Does home practice moderate the


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Does home practice moderate the

relationship between craving and

smoking?Independent Variable (X)

Craving

Dependent Variable (Y)Daily number

of cigarettes smoked

Moderator Variable (M)Mindfulness home

practice



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dissociated during treatmentBaseline

(Week 0)

End of

Treatment

(Week 4)

6-Week

Follow-Up

3-Month

Follow-Up

4-Month

Follow-Up

Craving (QSU)

X

Cigarette Use

r = 0.582

p < 0.001

N = 32

r = 0.126

p = 0.491

N=32

r = 0.474

p = 0.020

N = 25

r = 0.788

p < 0.00001

N=28

r = 0.768

p < 0.00001

N=29

p = .04

Predictor of Smoking r R2 p Effect size

Overall ModelBaseline Craving

Baseline Cigarette Use

End of Treatment Craving

Informal practice (days/wk)

Craving*Informal (days/wk)

0.735 0.5400.266

-0.053

0.208

-1.522

0.515

0.0010.591

0.53

0.652


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Reduction of craving scores with MT

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

Baseline End of Trmt 6-Week f/u 3-Month f/u 4-Month f/u

C

rav

ing

Sco

re(QSU) Abstainers

Non-Abstainers

*

p = 0.03

Elwafi et alDrug and Alcohol Dependence (in press)

Negative CuePositive Cue


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Neutral Cue(get in your car)

Negative Cue(get yelled at by your

boss)

Positive Cue(have a good meal or

sex)

Negative Affect

(stressed out)

Positive Affect

(happy or relaxed)

AVOIDANCE

OF CUES

SUBSTITUTEBEHAVIORS

CRAVINGre

in

Zinser 1992, Piasecki 1997, Carter 1999, Lazev 1999, Cox 2001, Robinson 2003, Bevins 2004, Baker 2004, Coo2004, Olausson 2004, Shiffman 2004, Carter 2008, Perkins 2010

Reinforcement of

Associative Memory/Habit

(smoking makes you feel

better)

SMOKE

Maintain or Increase

Positive Affect/Decrease

Negative Affect


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The destruction of craving conquers all

suffering.

-Dhammapada (354)


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Next steps in MT for addictions

Standardize evidence-basedapproaches

Web-based trainingsSmart phone apps


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Craving to Quit

(iPhone App)

21 day training for

smoking cessation

Daily modules In vivo exercises

Track progress

Experience Sampling Test efficacy

Improve treatment


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Mechanisms of Mindfulness?

Improved attentional focus (Jha 2007; Lutz 2009)

Improved cognitive flexibility (Moore 2009)

Reduced affective reactivity (Frewen 2008; Farb2010; Goldin 2010)

Modification or shifts away from

distorted or exaggerated self-view

(Teasdale 2002; Ramel 2004; Farb 2007; Goldin 2009)

Whats going on in the brain?


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How common is Mindlessness?

Prevalence: ~50% of waking life isspent mind-wandering.

No happier when mind iswandering vs. on task.

A wandering mind is an unhappy

mind.

Killingsworth 2010


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Overlap between DMN and

Self-referential processing

Whitfield-Gabrieli Neuroimage (2011)


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Mindfulness meditation practices

Concentration Loving-kindness

ChoicelessAwareness

In the next period, please pay

attention to the physical

sensation of the breath

wherever you feel it most

strongly in the body. Follow the

natural and spontaneous

movement of the breath, not

trying to change it in any way.

Just pay attention to it. If you

find that your attention haswandered to something else,

gently but firmly bring it back

to the physical sensation of the

breath.

Please think of a time when you

genuinely wished someone well

(pause). Using this feeling as a

focus, silently wish all beings

well, by repeating a few short

phrases of your choosing over

and over (for example: May all

beings be happy, may all beings

be healthy, may all beings be

safe from harm.)

In the next period please pay

attention to whatever comes

into your awareness, whether it

is a thought, emotion, or body

sensation. Just follow it until

something else comes into your

awareness, not trying to hold

onto it or change it in any way.

When something else comes

into your awareness, just payattention to it until the next

thing comes along.

Attention directed at

single (physical) object

Attention directed at

physical and mentalob ects

Attention focused, but not

directed to specific object


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Task of MT?

The task common to all of these

meditation techniques is the training

of attention away from self-referenceand mind-wandering and toward

ones immediate experience.


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Mechanisms of Mindfulness

Meditation?

Does meditation change brain

activation patterns? In the moment (state)

Over time (trait)


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Experienced meditator study

(n=12)Meditation hours

Mindfulness 7748.3+4250.5

Loving Kindness 1060.1+958.9Other 1756.8+2476.6

Total 10565.2+5148.9

Brewer et al 2011


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2 min

baseline

Trial Time Course

30 sec

Instructions

4.5 min

Choiceless

Awareness

Meditation

Concentration

Meditation

Loving

Kindness

Meditation

2x Trial (randomized between conditions)

Decreased DMN activity during


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Decreased DMN activity during

meditation in experienced

meditators

z = 21

(all meditations, Experienced > Novice)

x = -6

Brewer et al 2011


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Science is a way of trying not

to fool yourself. The firstprinciple is that you must not

fool yourself, and you are theeasiest person to fool.

-Richard Feynman


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1 min

baseline

Real-time meditation feedback

3 min

meditateactive

feedbackdummy

feedback

Real-time Neurofeeback


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Real time Neurofeeback(PCC ROI)

Run 1

Run 4

ExpertNovice

Decreasedself-related

activationIncreased

self-related

activation

Real-time Neurofeeback


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Real time Neurofeeback(PCC ROI)

Run 1 Run 4

Expert


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"Practice does not make perfect.Only perfect practice makes

perfect.

-Vince Lombardi


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What ingredients are needed

for mindfulness practice?

Pay attention


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RUN 1 RUN 2 RUN 3 RUN 4

felt a lot more

relaxed, like it

was less of a

struggle to

prevent my mind

from wandering

NOVICE MEDITATOR

Wh t i di t d d


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Pay attention

relaxed




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NOVICE MEDITATOR

RUN 1 RUN 2 RUN 3 RUN 4

Thinking

about the

breath

focused more on

the physical

sensation instead

of thinking in and

out

Wh t i di t d d


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Pay attention

Relax Drop theself



Mi df l i ld


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HOT COLD

Mindfulness may increase cold

while decreasing hot processingACC

dlPFCPCC

S


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Summary Stress leads to craving and unhealthy coping

(e.g. addictions) MT may be helpful with alcohol and cocaine

dependence

Changes psychological and physiological

responses to stress MT may help people quit smoking

More practice = better outcome

MT seems to decouple craving and smoking Practice may moderate this

Neural mechanisms of MT may involve DMN

Less selfishness = happier and healthier?


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Thanks for listening!

For more information:

www.cravingtoquit.com

Huffington Post blog (Judson Brewer)

www.ytnc.yale.edu

[email protected]


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Many Thanks!


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y

www.ytnc.yale.edu

FUNDING: NIDA (R03 DA029163-01A1, K12 DA00167, P50 DA09241), Mind and Life Institute,Yale Center for Clinical Investigation (UL1 RR024139),Yale Stress Center (UL1 DE019586-02),

VAMC MIRECC

SubjectsTheresa Babuscio

Keri BergquistSarah Bowen (UW)

Kathy Carroll

Neha Chawla (UW)

Justin Chen

Michael CohenTodd Constable

Cameron Deleone

Colin DeYoung

Hani Elwafi

Reza Farajian

Jeremy Gray

Michelle HampsonHayley Johnson

Yoona Kang

Hedy Kober

Cheryl Lacadie

Daniel LibbySarah Mallik

G. Alan Marlatt (UW)

Candace Minnix-Cotton

Charla Nich

Xenios Papademetris

Marc Potenza

Maolin QiuDeidre Reis

Bruce Rounsaville

Dustin Scheinost

Rajita Sinha

Tommy ThornhillAndrea Weinstein

Jochen Weber

Patrick Worhunsky


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