# Presentation: 538639

## 

Behavioral and Treatment Research on Marijuana Withdrawal and Dependence

Alan J. Budney 
University of Vermont

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

- Behavioral and Treatment Research on Marijuana Withdrawal and Dependence
*Alan J. Budney *
*University of Vermont*
- Supported by NIDA:
- DA08655, DA12471, DA12157, DA015186, T32DA07242

## Slide 2

## 	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 

**	****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 EpidemiologyNCS Study (Anthony et al. 1994)

- Clinical EpidemiologyNCS 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%

## Treatment Admissions (SAMHSA 2001)

- Treatment Admissions **(SAMHSA 2001)**

## 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 preparation
- Marijuana 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

- 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)

**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)

- 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 SymptomsBSI /SCL-90

- Psychiatric SymptomsBSI /SCL-90

- _	__	__	__	__	__	__M      T-score_
- Obsessive Compulsive		1.4	64
- Interpersonal Sensitivity	1.3	64
- Depression				1.5	65
- Anxiety				1.2	64
- Psychoticism			1.2	65
- Global Severity Index		1.2	66
**T-score above 62 is significantly elevated**

## Confidence in Ability to AbstainSCQ

- Confidence in Ability to AbstainSCQ

## Readiness to Change

## 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) 

**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			

- 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

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

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

## 

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.

- 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)

- Timecourse Study(Budney et al, 2003)

- 50 days, AB design outpatient study
- A:  5-day, Baseline (smoking-as-usual) Phase
- B:  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

## 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 Reports

- Aggression
- Irritability
- Restlessness
- Sleep Difficulty
- Strange Dreams

## Marijuana vs. Tobacco Withdrawal Vandrey et al. (in preparation)Total Withdrawal Discomfort

- Marijuana vs. Tobacco Withdrawal Vandrey et al. (in preparation)Total Withdrawal Discomfort

- *Sig diff by condition (p_<_.001); no interaction by group

## Irritability

- *Sig diff by condition (p_<_.001); no interaction by group

## Sleep Difficulty

- *Sig diff by condition (p_<_.001); no interaction by group

## Pharmacological SpecificityDronabinol (Oral THC) Attenuates Marijuana Withdrawal

**Pharmacological Specificity****Dronabinol (Oral THC) Attenuates Marijuana Withdrawal**

- Outpatient study
- 7 daily marijuana smokers
- ABACAD design
- Dronabinol (0, 10, 30mg tid)

## Withdrawal Discomfort Score

- ***

- **

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

## 	Symptoms suppressed by 
10mg and 30mg

Increased Aggression
Increased Anger
Irritability
Sleep Difficulty
Violent Outbursts

- 	Symptoms suppressed by
- 10mg and 30mg
- Increased Aggression
- Increased Anger
- Irritability
- Sleep Difficulty
- Violent Outbursts

## Symptoms suppressed 
by 30mg dose only:

Craving to Smoke Marijuana
Decreased Appetite
Nervousness/Anxiety

- Symptoms suppressed
- by 30mg dose only:
- Craving to Smoke Marijuana
- Decreased Appetite
- Nervousness/Anxiety

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

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

_**Common Symptoms**_
- Anger / Aggression
- Decreased Appetite or Weight Loss
- Irritability
- Nervousness / Anxiety
- Restlessness
- Sleep Difficulty or Unusual Dreaming

_**Less Common / Equivocal**_
- 	Chills
- 	Depressed Mood
- 	Stomach Pain
- 	Shakiness
- 	Sweating

## Treatment Outcome Research Adult Marijuana Dependence

**Treatment Outcome Research**** Adult Marijuana Dependence**

**Notes:**
To date, as with other more well-studied drug dependencies, behaviorally based treatment including coping skills training and relapse management have been shown to be effective.
We were interested in improving these treatments with the use of contingency management as Steve has shown with cocaine treatment, Thus .  
Alan’s previous study and our current trial are attempts to enhance outcomes 

## 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

- Treatment Studies% Abstinent at the End of Tx

## Treatment Outcome Research Summary to Date

**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

**Notes:**
To date, as with other more well-studied drug dependencies, behaviorally based treatment including coping skills training and relapse management have been shown to be effective.
We were interested in improving these treatments with the use of contingency management as Steve has shown with cocaine treatment, Thus .  
Alan’s previous study and our current trial are attempts to enhance outcomes 

## Primary Aim of our Treatment Research

- 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

**Notes:**
Growing literature which shows the effectiveness of the use of contingency management interventions with adult substance users.

Oftentimes, contingency management is combined with effective behavioral therapies to enhance treatment outcomes.

What’s interesting is that to date, no research exists using these interventions together with adolescents substance abusers.

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

- 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 program
- Provided urine specimens twice weekly
- *Post-tx follow-up assessments (12 months)

## Study 2

- Replication:  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)

**Notes:**

Second study was designed to examine the components of the BTV therapy to determine whether BT adds to the effectiveness of the vouchers.
Therefore there is a voucher only condition, in which clients receive no counseling.
	treatment acceptability, completion rates, etc. 

## Study 2Participants

- Study 2Participants

- MJ-dependent individuals seeking treatment
- 	N = 90
- 	69 men and 21 women
- 	Mean Age = 32.7 years
- Marijuana use
- Days used / month:	25.3 _+_ 7.4
- Times used / day: 	3.9 _+_ 3.2
- Years of regular use:	13.6 _+_ 10.5

## Treatment Acceptability(Budney et al., in prep) 

- Treatment Acceptability(Budney et al., in prep)

## Treatment Completion 

- Treatment Completion

## Continuous Abstinence 

- Continuous Abstinence

**Notes:**
Interaction, p = .04.   - significant change for voucher group only.

Note high level of clean at ETX.

## Marijuana Abstinence(marijuana-negative urinalysis)

- Marijuana Abstinence(marijuana-negative urinalysis)

**Notes:**
Interaction, p = .04.   - significant change for voucher group only.

Note high level of clean at ETX.

## Marijuana Abstinence (marijuana-negative urinalysis)

- Marijuana Abstinence (marijuana-negative urinalysis)

**Notes:**
Interaction, p = .04.   - significant change for voucher group only.

Note high level of clean at ETX.

## Days of Use per Month

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

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

## Relapse and Lapse(Moore and Budney, 2003)

- 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)

- % Lapse and Relapse(N = 82)

## 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

## CYT Adolescent StudyAbstinence at Discharge (CSAT: unpublished) 

- CYT Adolescent StudyAbstinence at Discharge (CSAT: unpublished)

## 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