Behavioral and Treatment Research on Marijuana Withdrawal and Dependence

Alan J. Budney University of Vermont

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

Marijuana is more similar than dissimilar to other drugs of abuse

Like other substances of abuse, a subset of persons who use marijuana go on to have problems…some not so serious, some serious

Clinical EpidemiologyNCS Study (Anthony et al. 1994)

Lifetime DependenceMarijuana Marijuana 4.2%4.2%Cocaine 2.7%Stimulants 1.7%Heroin 0.4%

Tobacco24.1%Alcohol 14.1%

Conditional Dependence

Heroin 23.1%

Cocaine 16.7%

Stimulants 11.2%

MarijuanaMarijuana 9.1% 9.1%

Tobacco31.9%

Alcohol 15.4%

Treatment Admissions (SAMHSA 2001)

0

10

20

30

40

50

60

Alcohol Cocaine Heroin Marijuana

199219962001

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.

Patient Characteristics

Age 32-35 (10.0) yrs

Male 75%

Employed (FT) 55-60%

Marital Status 55-60% never married

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%

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%

Problems Associated with Marijuana(MTP 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%

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

Psychiatric SymptomsBSI /SCL-90

M T-score Obsessive 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

Confidence in Ability to AbstainSCQ

0

20

40

60

80

Marijuana Cocaine

Readiness to Change

4

6

8

10

12

14

Marijuana Cocaine

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 to other substance dependent populations

• Measures of Readiness to Change and Confidence in Ability to Quit are not high

• Majority not dependent on other substances

Marijuana Withdrawal

Patient concerns and complaints

Old literature, both human and nonhuman

Withdrawal Study 1 (Budney et al. (1999)

Structured survey of 54 adults seeking treatment for marijuana dependence

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

a 0-3 scale (none to severe)

9.6 + 5.1 symptoms of at least mild severity

57%: > 5 symptoms of > moderate severity

47%: > 3 symptoms rated as severe

Common Withdrawal Symptoms

0

20

40

60

80

100Severity >1 Severity >2

Adolescents

Heavy Marijuana Users (> 15 days per month, N = 52)

0%

20%

40%

60%

80%

Shakiness Irritability Restless Headache Inc Anger

Mild Moderate Severe

These data suggest that marijuana withdrawal

is experienced by the majority of those

seeking treatment for marijuana dependence,

and its severity may warrant clinical

intervention.

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

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

*

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

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

Weight Change (kg)

-1.6-1.2-0.8-0.4

00.40.81.21.6

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

Abstinence Days

* * *

BL

Strange Dreams

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

*

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 more symptoms

- Duration of elevation 5-21 days for most symptoms

Collateral ReportsAggressionIrritability

RestlessnessSleep DifficultyStrange Dreams

Marijuana vs. Tobacco Withdrawal Vandrey 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<.001); no interaction by group

Irritability

0

0.2

0.4

0.6

0.8

1

1.2

1.4

B2 B3 B4 A1 A2 A3

TobaccoMarijuana

*Sig diff by condition (p<.001); no interaction by group

Sleep Difficulty

0

0.2

0.4

0.6

0.8

1

1.2

1.4

B2 B3 B4 A1 A2 A3

TobaccoMarijuana

*Sig diff by condition (p<.001); no interaction by group

Pharmacological SpecificityDronabinol (Oral THC) Attenuates

Marijuana Withdrawal

Outpatient study

7 daily marijuana smokers

ABACAD design

Dronabinol (0, 10, 30mg tid)

Withdrawal Discomfort Score

01

2345

67

Base Placebo Base 10mg Base 30mg

***

**

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

Symptoms suppressed by 10mg and 30mg

Increased AggressionIncreased AngerIrritabilitySleep DifficultyViolent Outbursts

Symptoms suppressed by 30mg dose only:

– Craving to Smoke Marijuana– Decreased Appetite– Nervousness/Anxiety

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

Common SymptomsAnger / AggressionDecreased Appetite or

Weight LossIrritabilityNervousness / AnxietyRestlessnessSleep Difficulty or

Unusual Dreaming

Less Common / Equivocal

Chills

Depressed Mood

Stomach Pain

Shakiness

Sweating

Treatment Outcome Research Adult Marijuana Dependence

Types of Treatment Studied

• Social Support Group

• CBT Group

• CBT Individual

• Brief Motivational

• Voucher-based Contingency Management

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

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

Primary Aim of our Treatment Research

Develop interventions that can enhance treatment outcomes

Application of Contingency Management

- voucher-based incentive program

Why contingency management?

• Growing literature on CM interventions with adult substance abusers

• CM usually combined with effective behavioral therapies to enhance outcomes

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)

Study 2Replication: vouchers enhance the effect of

behavioral therapy (BTV vs BT) (Budney et al. 2000)

To determine if effects endure post-treatment

To determine if behavioral counseling enhances the effect of the voucher program (V - BTV)

To examine the feasibility of providing the voucher program alone (V)

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 + 3.2 Years of regular use: 13.6 + 10.5

Treatment Acceptability(Budney et al., in prep)

0

20

40

60

80

100

BTBTVVouchers

Treatment Completion

0

20

40

60

80

100

BTBTVVouchers

Continuous Abstinence

0

10

20

30

40

50

60

>=2 weeks >=4 weeks >=6 weeks* (p <.05)

>=8 weeks >10 weeks

BT BTV Voucher

Marijuana Abstinence(marijuana-negative urinalysis)

0

10

20

30

40

50

wk1

wk2

wk3

wk4

wk5

wk6

wk7

wk8

wk9

wk10

wk11

wk12

wk13

wk14

Voucher BT BTV

Marijuana Abstinence (marijuana-negative urinalysis)

0

10

20

30

40

50

ETX 1-Month

3-Month

6-Month

9-Month

12-month

BT BTV Voucher

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

MTP Results: First 4 Months, % of Days Smoked Marijuana (N=398)

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

BLW

k2W

k4W

k6W

k8

Wk10

Wk12

Wk14

Wk16

% o

f D

ays

Smok

ed p

er W

eek

DTC

BTET

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

% Lapse and Relapse(N = 82)

0

10

20

30

40

50

60

70

80

One Month Three Month Six Month Relapse/6month

Adolescent Treatment

• Limited support for behavioral and family-based treatments with adolescents

• Only one study specifically focused on marijuana

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

CYT: Marijuana Use

0

10

20

30

40

50

0 3 6 9Months from Intake

MET/CBT5 ACRA MDFT MET/CBT12 MET/CB12+ FSN

CYT Adolescent StudyAbstinence at Discharge

(CSAT: unpublished)

0

10

20

30

40

M/CBT5 M/CBT12 FSN CRA MDFT

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 and vouchers can enhance treatment outcome

Future Directions

• Continue search for more effective treatments

• Combine psychosocial treatments• Medication development

– Substitutes– Antagonists– Target mood

• Combine medication and psychosocial

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