Behavioral and Treatment Research on Marijuana Withdrawal and Dependence Alan J. Budney

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

3. 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

4. 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% Clinical EpidemiologyNCS Study (Anthony et al. 1994)

5. Treatment Admissions(SAMHSA 2001)

6. 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.

7. Patient Characteristics Age 32-35 (10.0) yrs Male 75% Employed (FT) 55-60% Marital Status 55-60% never married

8. 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%

9. 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%

10. 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%

11. 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

12. 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 Psychiatric SymptomsBSI /SCL-90

13. Confidence in Ability to AbstainSCQ

14. Readiness to Change

15. 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

16. Marijuana Withdrawal Patient concerns and complaints Old literature, both human and nonhuman

17. 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)

18. 9.6 + 5.1 symptoms of at least mild severity 57%: > 5 symptoms of > moderate severity 47%: > 3 symptoms rated as severe

19. Common Withdrawal Symptoms

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

21. 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.

22. 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

23. Withdrawal Discomfort Score

28. 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

29. Collateral Reports Aggression Irritability Restlessness Sleep Difficulty Strange Dreams

30. Marijuana vs. TobaccoWithdrawal Vandrey et al. (in preparation)Total Withdrawal Discomfort *Sig diff by condition (p<.001); no interaction by group

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

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

33. Pharmacological SpecificityDronabinol (Oral THC) Attenuates Marijuana Withdrawal Outpatient study 7 daily marijuana smokers ABACAD design Dronabinol (0, 10, 30mg tid)

34. Withdrawal Discomfort Score *** ** * diff from base, * diff from 10mg, * diff from 30mg

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

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

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

38. Treatment Outcome Research Adult Marijuana Dependence

39. Types of Treatment Studied • Social Support Group • CBT Group • CBT Individual • Brief Motivational • Voucher-based Contingency Management

40. Study CBT MI CBT+V V Steph (1994) 63% Steph (2000) 44% 39% Budney (2000) 10% 5% 35% Copeland (2001) - - MTP (in press) 27% 16% Budney (in prep) 27% 47% 40% Range 10-63% 5-39% 35-47% 40% Treatment Studies% Abstinent at the End of Tx

41. 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

42. Primary Aim of our Treatment Research Develop interventions that can enhance treatment outcomes Application of Contingency Management - voucher-based incentive program

43. Why contingency management? • Growing literature on CM interventions with adult substance abusers • CM usually combined with effective behavioral therapies to enhance outcomes

44. 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)

45. 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)

46. 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

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

48. Treatment Completion

49. Continuous Abstinence

50. Marijuana Abstinence(marijuana-negative urinalysis)