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Behavioral and Treatment Researchon Marijuana Withdrawal and

Dependence

Alan J. BudneyUniversity of Vermont

Supported by NIDA:DA08655, DA12471, DA12157, DA015186, T32DA07242

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Marijuana is more similar thandissimilar to other drugs of abuse

Like other substances of abuse, a subsetof persons who use marijuana go on tohave problemssome not so serious,some serious

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Clinical Epidemiology NCS Study (Anthony et al. 1994)

Lifetime Dependence Marijuana 4.2%

Cocaine 2.7%Stimulants 1.7%Heroin 0.4%

Tobacco 24.1%Alcohol 14.1%

Conditional Dependence Heroin 23.1%

Cocaine 16.7%Stimulants 11.2%

Marijuana 9.1%

Tobacco 31.9%Alcohol 15.4%

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Treatment Admissions(SAMHSA 2001)

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Treatment Outcome Studies

- 4 controlled studies (Adults)Stephens, Roffman et al. (1994, 2000)

Budney, et al. (2000)Copeland et al. (2001) Australia

- 2 others in press or in preparationMarijuana Treatment Project(multi-site study)Budney et al.

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Patient Characteristics

Age 32-35 (10.0) yrs

Male 75%Employed (FT) 55-60%Marital Status 55-60% never married

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Marijuana Dependence Severity

# of DSM-III-R criteria 6.3 (1.8)Continued Use 97%

Cut Down 86%Larger Amounts 80%Excessive time 73%Withdrawal 75% Tolerance 63%Reduced Activities 41%

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Marijuana Use

Days Used/mo 25.6 (7.2)

Times per day 3.9 (2.5) Years of Use 13.8 (8.3)$ spent (mo) $123 (185)

Cigarette smoker 46%

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Problems Associated with Marijuana (M TP Study, 2000)

Feeling Bad or Guilty 90%Low Energy Level 86%

Procrastination 86%Memory loss 76%Low productivity 75%

Low self-esteem/confidence 70%Interpersonal 58%Financial 49%

Family 44%

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Reasons for Quitting(Stephens et al, 1993)

Self-control Health concerns Self-image Not socially acceptable

Legal problems Direct social pressure (family, children) Drug testing at work

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Psychiatric SymptomsBSI /SCL-90

M T-scoreObsessive Compulsive 1.4 64Interpersonal Sensitivity 1.3 64Depression 1.5 65Anxiety 1.2 64Psychoticism 1.2 65Global Severity Index 1.2 66T-score above 62 is significantly elevated

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Confidence in Ability to Abstain

SCQ

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Readiness to Change

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Adult Treatment Seekers

Meet 5-7 DSM-III-R criteria (Budney, 2000, 2003;Stephens et al., 2000, 2002, Copeland et., 2001)

Associated problems are comparable toother substance dependent populations

Measures of Readiness to Change andConfidence in Ability to Quit are not high

Majority not dependent on other substances

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Marijuana Withdrawal

Patient concerns and complaints

Old literature, both human and nonhuman

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Withdrawal Study 1 (Budney et al. (1999)

Structured survey of 54 adults seekingtreatment for marijuana dependence

Marijuana Withdrawal Checklist (22 items) rate perception of withdrawal severity on

a 0-3 scale (none to severe)

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9.6 + 5.1 symptoms of at least mild severity

57%: > 5 symptoms of > moderate severity

47%: > 3 symptoms rated as severe

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Common Withdrawal Symptoms

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AdolescentsHeavy Marijuana Users

(> 15 days per month, N = 52)

0%

20%

40%

60%

80%

Shakines s Irritability Res tle ss He adache Inc Ange

Mild Moderate Se ve re

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These data suggest that marijuana withdrawalis experienced by the majority of thoseseeking treatment for marijuana dependence,and its severity may warrant clinicalintervention.

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Timecourse Study(Budney et al, 2003)

50 days, AB design outpatient studyA: 5-day, Baseline (smoking-as-usual) PhaseB: 45-day, Marijuana Abstinence Phase

2 groups 18 chronic, heavy marijuana smokers

(>25/month) 12 ex-marijuana smokers (abstinent >1 year)

Previous heavy use

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Withdrawal Discomfort Score

0

2

4

6

8

10

1-5 1-3 4-6 7-9 10-12

13-15

16-18

19-21

22-24

25-27

28-30

31-33

34-36

37-39

40-42

43-45

Abstinence Days

*

*

**

*

BL

*

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Restlessness

00,20,40,60,8

11,21,4

1-5 1-3 4-6 7-9 10-12

13-15

16-18

19-21

22-24

25-27

28-30

31-33

34-36

37-39

40-42

43-45

Abstinence Days

*

*

*

BL

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Aggression

00.20.40.60.8

11.21.4

1-5 1-3 4-6 7-9 10-12

13-15

16-18

19-21

22-24

25-27

28-30

31-33

34-36

37-39

40-42

43-45

Abstinence Days

**

BL

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Weight Change (kg)

-1.6-1.2-0.8-0.4

0

0.40.81.21.6

1-5 1-2 3-4 7 10 14 17 21 24 28 31 35 38 42 45

Abstinence Days

* * *

BL

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Strange Dreams

00.20.40.60.8

1

1.21.4

1-5 1-3 4-6 7-9 10-12

13-15

16-18

19-21

22-24

25-27

28-30

31-33

34-36

37-39

40-42

43-45

Abstinence Days

*

*

*

*

*

***

*

*

**

*

**

BL

*

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Timecourse and Magnitude

- Peak Effects occur between Days 2-6- 10%-45% increases across symptoms

(+ 0.4 to 1.8 pt on the 4-pt severity scale)

- 78% of Ss show > 1-pt change on 5 or moresymptoms

- Duration of elevation 5-21 days for mostsymptoms

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Collateral ReportsAggressionIrritability

RestlessnessSleep DifficultyStrange Dreams

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Marijuana vs. Tobacco WithdrawalVandrey et al. (in preparation)

Total Withdrawal Discomfort

0

2

4

6

8

10

B2 B3 B4 A1 A2 A3

TobaccoMarijuana

*Sig diff by condition (p

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Irritability

0

0.2

0.4

0.6

0.81

1.2

1.4

B2 B3 B4 A1 A2 A3

TobaccoMarijuana

*Sig diff by condition (p

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Sleep Difficulty

0

0.2

0.4

0.6

0.81

1.2

1.4

B2 B3 B4 A1 A2 A3

TobaccoMarijuana

*Sig diff by condition (p

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Pharmacological Specificity

Dronabinol (Oral THC) AttenuatesMarijuana Withdrawal

Outpatient study7 daily marijuana smokers

ABACAD designDronabinol (0, 10, 30mg tid)

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Withdrawal Discomfort Score

01

234567

Base Placebo Base 10mg Base 30mg

***

**

* diff from base, * diff from 10mg, * diff from 30mg

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Symptoms suppressed by 30mg dose only :

Craving to Smoke Marijuana Decreased Appetite Nervousness/Anxiety

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Proposed DSM Criteria(Budney et al ., in press AJP)

Common Symptoms Anger / AggressionDecreased Appetite or

Weight LossIrritability

Nervousness / Anxiety

RestlessnessSleep Difficulty orUnusual Dreaming

Less Common / Equivocal Chills

Depressed MoodStomach PainShakinessSweating

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Treatment Outcome Research

Adult Marijuana Dependence

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Types of Treatment Studied

Social Support Group CBT Group CBT Individual Brief Motivational Voucher-based Contingency Management

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Treatment Studies

% Abstinent at the End of Tx

16%27%MTP (in press)

--Copeland (2001)

40%35-47%5-39%10-63%Range

40%

V

47%27%Budney (in prep)

35%5%10%Budney (2000)39%44%Steph (2000)

63%Steph (1994)

CBT+VMICBTStudy

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Treatment Outcome Research

Summary to Date

Types of effective treatments are similar to

those observed with other substances...- behavioral-based and motivational

therapies

Magnitude of treatment effect appears similar

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Primary Aim of our

Treatment Research

Develop interventions that can enhancetreatment outcomes

Application of Contingency Management- voucher-based incentive program

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Why contingency management?

Growing literature on CM interventionswith adult substance abusers

CM usually combined with effective behavioral therapies to enhance outcomes

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Behavioral Treatment - Study 2(Budney et al. in prep)

Three Group Design

- Behavioral coping-skills (BT)

- BT plus vouchers (BTV)- Vouchers only (V)

14-week outpatient programProvided urine specimens twice weekly

*Post-tx follow-up assessments (12 months)

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Study 2Participants

MJ-dependent individuals seeking treatment N = 9069 men and 21 womenMean Age = 32.7 years

Marijuana useDays used / month: 25.3 + 7.4Times used / day: 3.9 + 3.2Years of regular use: 13.6 + 10.5

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Treatment Acceptability(Budney et al., in prep)

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Treatment Completion

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Continuous Abstinence

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Marijuana Abstinence(marijuana-negative urinalysis)

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Marijuana Abstinence(marijuana-negative urinalysis)

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Days of Use per Month

0

10

20

30

Baseline M1-TX M2-TX M3-TX M1-FU M3-FU M12-FU

Voucher BT BTV

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MTP Results: First 4 Months,

% of Days Smoked Marijuana (N=398)

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Relapse and Lapse(Moore and Budney, 2003)

N = 152 Adult MJ-Dependent Treatment Seekers Across two trials

N= 82 (54%) achieved 2 wks of abstinence

Self-report verified by urine test

90% achieved this 2-wk period with first 6 weeks

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% Lapse and Relapse(N = 82)

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Adolescent Treatment

Limited support for behavioral and family- based treatments with adolescents

Only one study specifically focused onmarijuana

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CYT Adolescent Study

Evaluate 5 outpt treatments for marijuana abuse 600 adolescents 83% male 61% white

Age: M=16yrs (13-18yr) 62% juvenile justice system referrals Met at least 1 DSM abuse or dependence criteria

and used marijuana in past 90 days

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CYT: Marijuana Use

CYT Ad l t St d

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CYT Adolescent StudyAbstinence at Discharge

(CSAT: unpublished)

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NIDA-Funded Trial

Random assignment to one of two 14-wk treatments

CBT + Contingency Management and Parent Training

(Vouchers, Consequences)

CBT + Family Drug Education

Determine if combination of parent training andvouchers can enhance treatment outcome

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Future Directions

Continue search for more effectivetreatments

Combine psychosocial treatments Medication development

Substitutes Antagonists Target mood

Combine medication and psychosocial

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Thanks to the Staff at the

Treatment Research Center Heath Rocha Krestin Radonovich Doris Ogden Pamela Novy

Allyson McGuire Andrea DeCoster Betsy Bahrenburg Jason Revoir Katherine Donahue Ann Greer

** John Hughes, Brent Moore, Catherine Stanger,Ryan Vandrey, Stephen Higgins