Craving to quit: insights from studies of mindfulness training for alcohol, cocaine and nicotine dependence

Judson Brewer MD PhD Medical Director Yale Therapeutic Neuroscience Clinic Assistant Professor Department of Psychiatry Yale University School of Medicine www.ytnc.yale.edu

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” meditator’s brain differ from anyone else’s? • How can neuroscience improve treatment of stress and related disorders?

Stress
• Consequences of the failure to respond appropriately 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)

Stress and Addiction
• Acute stress leads to increases in selfadministration of drugs such as amphetamines (Bradley 1989), cocaine (Kalivas 1989), and alcohol (Nash
1988)

• Stress induces drug craving (Sinha 2005) and consumption (De wit 2003) • Stressful life events are associated with nicotine dependence (Balk 2009) • Negative affect drives continuation of smoking
(Markou 1998)

Stress and Relapse
• Stressful events, negative emotions and psychological distress are frequently cited reasons for 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 (Shiffman
1996)

Sensory Information

Changes how we see the world

Sensory Information

Changes how we see the world

Sensory Information

“Craving, not having, is the mother of a reckless giving of oneself.”
-Eric Hoffer

Positive Cue
(have a good meal or sex)

Neutral Cue
(get in your car)

Negative Cue
(get yelled at by your boss)

AVOIDANCE OF CUES
Positive Affect (happy or relaxed) re Negative Affect (stressed out)

CRAVING

Automated
in

SMOKE
Maintain or Increase Positive Affect/Decrease Negative Affect Reinforcement of Associative Memory/Habit (smoking makes you feel better)

SUBSTITUTE BEHAVIORS

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

“I can't get no satisfaction I 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 get no…”
-Mick Jaggar

Self-control: competing systems
• Affective (self-referential?)/hot processing
– involves self-referential valuation, is automatic and unplanned, and influences behavior through impulses (Weber
2004, 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; Kober
2010)

• 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; Steinbeis
2012)

How to improve the balance between cold and hot processing?

HOT

COLD

“There is no end of craving. Hence contentment alone is the best way to happiness.”
-Sivananda Saraswati

Overview of Mindfulness
Two Component Definition: 1) Self-regulation of attention so that it is maintained on immediate experience, thereby allowing for increased recognition of mental events in the present moment. 2) Adopting a particular orientation toward one’s experiences in the present moment, characterized by curiosity, openness, and acceptance.
Bishop 2004

Sensory Information

Trigger

Applied mindfulness: RAIN
• RECOGNIZE – “Oh that’s a craving” • ACCEPT/ALLOW – See if you are resisting the experience • INVESTIGATE – “what’s happening in my body right now?” • NOTE – Label or mentally note the body sensations from moment to moment

Pilot Study of MT for Addictions
• Mindfulness Based Relapse Prevention vs. CBT for alcohol and/or cocaine dependence – randomized controlled trial – No previous trials of MT as primary treatment – No previous trials of MT vs. active control group • Is it well-tolerated? (yes) • Does it stack up to gold standard treatment (yes) • Does it change psychological and physiological responses to stress? (yes)

Brewer et al 2009

Does mindfulness training work for smoking cessation?

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%)

Mindfulness Training for Smoking
1 month outpatient training (twice weekly): • Emphasis on awareness, acceptance of and working with craving/wanting • Setting aspirations: work toward a quit date at the end 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)

Screened by Phone (n=757)
Eligible by phone screen but not interested or lost to follow-up (n=212) Did not meet inclusion/exclusion criteria (n=459)

Assessed for Eligibility (n=134)
Dropped out before randomization (n=12) Did not meet inclusion/exclusion criteria (n=21) Force randomized to MT*** (n=3)
*Attended 6 out of 8 sessions **Excluded from all analyses due to VA regulations ***Mistakenly force randomized to MT

Randomized (n=88)
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)* Completed 6 week follow-up interview (n=33) (87%) Completed 12 week follow-up interview (n= 32) (84%) Completed 17 week follow-up interview (n= 33) (87%) 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)* Completed 6 week follow-up interview (n= 27) (82%) Completed 12 week follow-up interview (n= 29) (88%) Completed 17 week follow-up interview (n= 29) (88%)

Included in Analysis (n=46) Excluded from analysis (**incarcerated, n=1)

Included in Analysis (n=41)

Brewer et al 2011

Greater reduction in smoking with MT vs. Freedom from Smoking
Average Cigarettes/day
20 18 16 14 12 10 8 6 4 2 0

FFS MTS

Group*Time F=11.11, p=.001

0 1

1 2

2 3

3 4

4 5
Brewer et al 2011

Treatment week

Greater smoking abstinence with MT vs. Freedom from Smoking
40

Point Prevalence Abstinence (%)

35

*
**

MT

FFS

30

25

20

15

10

5

*p = .063 **p = .012

0

End of Treatment

17 week follow-up

Brewer et al 2011

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: (Ferguson
2006)

• For each 1 SD increase in craving score on target quit 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%

Working hypothesis
• Hypothesis: MT works by decoupling craving 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

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: (Ferguson
2006)

• For each 1 SD increase in craving score on target quit 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%

Working hypothesis
• Hypothesis: MT works by decoupling craving 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

Craving and cigarette use become dissociated during treatment
Baseline (Week 0) Craving (QSU) X Cigarette Use End of Treatment (Week 4) 6-Week Follow-Up 3-Month Follow-Up 4-Month Follow-Up

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

Mindfulness practice moderates dissociation
Predictor of Smoking r R2
0.540
0.266 -0.053 0.208 -1.522 0.515

β

p
0.001 0.591 0.53 0.652 <0.0001 0.026

Effect size

0.735 Overall Model Baseline Craving Baseline Cigarette Use End of Treatment Craving Informal practice (days/wk) Craving*Informal (days/wk)

1.17

Elwafi et al Drug and Alcohol Dependence (in press)

MT practice modifies relationship between craving and smoking
Variable
Baseline Week 4
QSU QSU QSU+ Formal
(days/week)

r
0.582 0.126

r2
0.339 0.016

p
< 0.0001 0.491

df
1, 31 2, 31 2, 31 2, 31 2, 31 2, 31

b
3.41 0.41 0.47, -1.33 0.35, -0.99 0.33, -0.009 0.56, -0.03

b
(standardi zed)

p
< 0.0001 0.491 0.358, 0.001 0.516, 0.008 0.533, 0.008 0.273, 0.001

0.58 0.13 0.14, -0.55 0.11, -0.47 0.10, -0.47 0.17, -0.55

0.561

0.315

0.004

QSU+ Informal
(days/week)

0.484

0.234

0.021

QSU+ Formal
(total minutes)

0.482

0.232

0.022

QSU+ Informal
(total times)

0.566

0.320

0.004

Moderation in a single slide
(as taught by a psychiatrist) Independent Variable (X) “psychotherapy”

A moderator (M) is a variable that alters the direction or strength of the relation between a predictor and Moderator Variable (M) outcome (Frazier 2004)

“gender”

Dependent Variable (Y) “depression”

Does home practice moderate the relationship between craving and smoking?
Independent Variable (X) “Craving” Moderator Variable (M) “Mindfulness home practice” Dependent Variable (Y) “Daily number of cigarettes smoked”

Craving and cigarette use become dissociated during treatment
Baseline (Week 0) Craving (QSU) X Cigarette Use r = 0.582 p < 0.001 N = 32 End of Treatment (Week 4) r = 0.126 p = 0.491 N=32 6-Week Follow-Up r = 0.474 p = 0.020 N = 25 3-Month Follow-Up r = 0.788 p < 0.00001 N=28 4-Month Follow-Up r = 0.768 p < 0.00001 N=29

p = .04

Mindfulness practice moderates dissociation
Predictor of Smoking r R2
0.540
0.266 -0.053 0.208 -1.522 0.515

β

p
0.001 0.591 0.53 0.652 <0.0001 0.026

Effect size

0.735 Overall Model Baseline Craving Baseline Cigarette Use End of Treatment Craving Informal practice (days/wk) Craving*Informal (days/wk)

1.17

Elwafi et al Drug and Alcohol Dependence (in press)

Reduction of craving scores with MT
4.5

Craving Score (QSU)

4 3.5 3 2.5 2 1.5 1 0.5 0
Baseline End of Trmt

Abstainers

Non-Abstainers

*
p = 0.03
6-Week f/u 3-Month f/u 4-Month f/u

Elwafi et al Drug and Alcohol Dependence (in press)

Positive Cue
(have a good meal or sex)

Neutral Cue
(get in your car)

Negative Cue
(get yelled at by your boss)

AVOIDANCE OF CUES
Positive Affect (happy or relaxed) re Negative Affect (stressed out)

CRAVING SMOKE
Maintain or Increase Positive Affect/Decrease Negative Affect Reinforcement of Associative Memory/Habit (smoking makes you feel better)

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

in

SUBSTITUTE BEHAVIORS

“The destruction of craving conquers all suffering.”

-Dhammapada (354)

Next steps in MT for addictions
• Standardize evidence-based approaches
– Web-based trainings – Smart phone apps

Craving to Quit (iPhone App)
• 21 day training for smoking cessation • Daily modules • In vivo exercises • Track progress • Experience Sampling
– Test efficacy – Improve treatment

Mechanisms of Mindfulness?
• Improved attentional focus (Jha 2007; Lutz 2009) • Improved cognitive flexibility (Moore 2009) • Reduced affective reactivity (Frewen 2008; Farb
2010; Goldin 2010)

• Modification or shifts away from distorted or exaggerated self-view
(Teasdale 2002; Ramel 2004; Farb 2007; Goldin 2009)

• What’s going on in the brain?

How common is Mindlessness?
• Prevalence: ~50% of waking life is spent mind-wandering. • No happier when mind is wandering vs. on task. • “A wandering mind is an unhappy mind.”
Killingsworth 2010

Overlap between DMN and Self-referential processing

Whitfield-Gabrieli Neuroimage (2011)

Mindfulness meditation practices
Concentration
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 has wandered to something else, gently but firmly bring it back to the physical sensation of the breath.

Lovingkindness
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.)

Choiceless Awareness
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 pay attention to it until the next thing comes along.

Attention directed at single (physical) object

Attention directed at physical and mental objects

Attention focused, but not directed to specific object

Task of MT?
• The “task” common to all of these meditation techniques is the training of attention away from self-reference and mind-wandering and toward one’s immediate experience.

Mechanisms of Mindfulness Meditation?
• Does meditation change brain activation patterns? – In the moment (state) – Over time (trait)

Experienced meditator study (n=12)
Meditation hours Mindfulness Loving Kindness Other Total 7748.3+4250.5 1060.1+958.9 1756.8+2476.6 10565.2+5148.9

Brewer et al 2011

Trial Time Course
baseline Instructions

2 min
30 sec

Choiceless Loving Concentration Awareness Kindness Meditation Meditation
4.5 min

2x Trial (randomized between conditions)

Decreased DMN activity during meditation in experienced meditators
(all meditations, Experienced > Novice)

x = -6

z = 21
Brewer et al 2011

x = -6
BOLD signal change (%)
0.3

z = 21

0.3

0.1

0.1

-0.1

-0.1

-0.3

-0.3

-0.5

Meditators

Controls

-0.5

Meditators

Controls

“Science is a way of trying not to fool yourself. The first principle is that you must not fool yourself, and you are the easiest person to fool.”
-Richard Feynman

Real-time meditation feedback

baseline
“active” “dummy” meditate feedback feedback 3 min

1 min

Real-time Neurofeeback (PCC ROI)
Novice Run 1
Decreased self-related activation Increased self-related activation

Expert

Run 4

Real-time Neurofeeback (PCC ROI) Expert

Run 1

Run 4

"Practice does not make perfect. Only perfect practice makes perfect.”
-Vince Lombardi

What ingredients are needed for mindfulness practice?

Pay attention

NOVICE MEDITATOR
“felt a lot more relaxed, like it was less of a struggle to prevent my mind from wandering”

RUN 1

RUN 2

RUN 3

RUN 4

What ingredients are needed for mindfulness practice?

Pay attention relaxed

NOVICE MEDITATOR
Thinking about the breath
”focused more on the physical sensation instead of thinking in and out”

RUN 1

RUN 2

RUN 3

RUN 4

What ingredients are needed for mindfulness practice?

Pay attention
Relax Drop the self

Mindfulness may increase cold while decreasing hot processing
ACC

PCC

dlPFC

HOT

COLD

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?

Thanks for listening!
• For more information: – www.cravingtoquit.com – Huffington Post blog (Judson Brewer) – www.ytnc.yale.edu – judson.brewer@yale.edu

Many Thanks! Subjects
Theresa Babuscio Keri Bergquist Sarah Bowen (UW) Kathy Carroll Neha Chawla (UW) Justin Chen Michael Cohen Todd Constable Cameron Deleone Colin DeYoung Hani Elwafi Reza Farajian Jeremy Gray Michelle Hampson Hayley Johnson Yoona Kang Hedy Kober Cheryl Lacadie Daniel Libby Sarah Mallik G. Alan Marlatt (UW) Candace Minnix-Cotton Charla Nich Xenios Papademetris Marc Potenza Maolin Qiu Deidre Reis Bruce Rounsaville Dustin Scheinost Rajita Sinha Tommy Thornhill Andrea Weinstein Jochen Weber Patrick Worhunsky

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

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