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Cannabis Youth Treatment (CYT) Trials: 12 and 30 Month Main Findings. Michael Dennis, Ph.D. Chestnut Health Systems Bloomington, IL
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Cannabis Youth Treatment (CYT) Trials: 12 and 30 Month Main Findings Michael Dennis, Ph.D. Chestnut Health Systems Bloomington, IL Presentation for the Adolescent Treatment Initiative, Concord, NH, April 20, 2005. Sponsored by New Futures. The content of this presentations are based on treatment & research funded by the Center for Substance Abuse Treatment (CSAT), Substance Abuse and Mental Health Services Administration (SAMHSA) under contract 270-2003-00006 and several individual grants. The opinions are those of the author and do not reflect official positions of the consortium or government. Available on line at www.chestnut.org/LI/Posters or by contacting Joan Unsicker at 720 West Chestnut, Bloomington, IL 61701, phone: (309) 827-6026, fax: (309) 829-4661, e-Mail: junsicker@Chestnut.Org
AcknowledgementThis presentation is based on the work, input and contributions from several other people including: Nancy Angelovich, Tom Babor, Laura (Bunch) Brantley, Joseph A. Burleson, George Dent, Guy Diamond, James Fraser, Michael French, Rod Funk, Mark Godley, Susan H. Godley, Nancy Hamilton, James Herrell, David Hodgkins, Ronald Kadden, Yifrah Kaminer, Tracy L. Karvinen, Pamela Kelberg, Jodi (Johnson) Leckrone, Howard Liddle, Barbara McDougal, Kerry Anne McGeary, Robert Meyers, Suzie Panichelli-Mindel, Lora Passetti, Nancy Petry, M. Christopher Roebuck, Susan Sampl, Meleny Scudder, Christy Scott, Melissa Siekmann, Jane Smith, Zeena Tawfik, Frank Tims, Janet Titus, Jane Ungemack, Joan Unsicker, Chuck Webb, James West, Bill White, Michelle White,Caroline Hunter Williams, the other CYT staff, and the families who participated in this study. This presentation was supported by funds and data from the Center for Substance Abuse Treatment (CSAT’s) Persistent Effects of Treatment Study (PETS, Contract No. 270-97-7011) and the Cannabis Youth Treatment (CYT) Cooperative Agreement (Grant Nos. TI11317, TI11320, TI11321, TI11323, and TI11324). The opinions are those of the author and steering committee and do not reflect official positions of the government .
CYT Cannabis Youth Treatment Randomized Field Trial Coordinating Center: Chestnut Health Systems, Bloomington, IL, and Chicago, IL University of Miami, Miami, FL University of Conn. Health Center, Farmington, CT Sites: Univ. of Conn. Health Center, Farmington, CT Operation PAR, St. Petersburg, FL Chestnut Health Systems, Madison County, IL Children’s Hosp. of Philadelphia, Phil. ,PA Sponsored by: Center for Substance Abuse Treatment (CSAT), Substance Abuse and Mental Health Services Administration (SAMHSA), U.S. Department of Health and Human Services
Marijuana • Use is starting at younger ages • Is at an historically high level among adolescents • Potency increased 3-fold from 1980 to 1997 • Is three times more likely to lead to dependence among adolescents than adults • Is associated with many health, mental and behavioral problems • Is the leading substance mentioned in adolescent emergency room admissions and autopsies
Treatment • Marijuana related admissions to adolescent substance abuse treatment increased by 115% from 1992 to 1998 • Over 80% of adolescents entering treatment in 1998 had a marijuana problem • Over 80% are entering outpatient treatment • Over 75% receive less than 90 days of treatment (median of 6 weeks) • Evaluations of existing adolescent outpatient treatment suggest that last than 90 days of outpatient treatment is rarely effective for reducing marijuana use.
Purpose of CYT • To learn more about the characteristics and needs of adolescent marijuana users presenting for outpatient treatment. • To adapt evidence-based, manual-guided therapies for use in 1.5 to 3 month adolescent outpatient treatment programs in medical centers or community based settings. • To field test the relative effectiveness, cost, cost-effectiveness, and benefit cost of five interventions targeted at marijuana use and associated problems in adolescents. • To provide validated models of these interventions to the treatment field in order to address the pressing demands for expanded and more effective services.
Design • Target Population: Adolescents with marijuana disorders who are appropriate for 1 to 3 months of outpatient treatment. • Inclusion Criteria: 12 to 18 year olds with symptoms of cannabis abuse or dependence, past 90 day use, and meeting ASAM criteria for outpatient treatment • Data Sources: self report, collateral reports, on-site and laboratory urine testing, therapist alliance and discharge reports, staff service logs, and cost analysis. • Random Assignment: to one of three treatments within site in two research arms and quarterly follow-up interview for 12 months • Long Term Follow-up: under a supplement from PETSA follow-up was extended to 30 months (42 for a subsample)
Two Trials or Study Arms Trial 1 Trial 2 Incremental Arm Alternative Arm Randomly Assigns to: Randomly Assigns to: MET/CBT5 MET/CBT5 Motivational Enhancement Therapy/ Motivational Enhancement Therapy/ Cognitive Behavioral Therapy (5 weeks) Cognitive Behavioral Therapy (5 weeks) MET/CBT12 ACRA Motivational Enhancement Therapy/ Adolescent Community Reinforcement Approach(12 weeks) Cognitive Behavioral Therapy (12 weeks) MDFT FSN Family Support Network Multidimensional Family Therapy Plus MET/CBT12 (12 weeks) (12 weeks) Source: Dennis et al, 2002
2 2 2 10 6 3 10 10 Type of Service MET/ CBT5 MET/ CBT12 FSN ACRA MDFT 2 3 4 2 6 6 5 12 22 14 15 As needed As needed As needed 5 5 6-7 12-13 12 12 22+ 22+ 12-13 12-13 14+ 14+ 15+ 12-13 15+ Contrast of the Treatment Structures Individual Adolescent Sessions CBT Group Sessions Individual Parent Sessions Family Sessions/Home Visits Parent Education Sessions Total Formal Sessions Case management/ Other Contacts Total Expected Contacts Total Expected Hours Total Expected Weeks Source: Diamond et al, 2002
Actual Treatment Received by Condition ACRA and MDFT both rely on individual, family and case management instead of group FSN adds multi family group, family home visits and more case management And MDFT using more family therapy MET/CBT12 adds 7 more sessions of group With ACRA using more individual therapy Source: Dennis et al, under review
Variation in Family services Variation in wrap around services Similarity in direct services Interventions Also Differ in Content 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Direct Family External Total (3-6,9-10,19,99) (1,7-8,15) (2,11-14,16-17) (all) MET/CBT5 FSNM MET/CBT5 MDFT MET/CBT12 ACRA Source: CYT data
Less than average for 6 weeks Less than average for 12 weeks $3,495 $1,776 NTIES Est (6.7 weeks) NTIES Est.(13.1 weeks) Average Episode Cost ($US) of Treatment |--------------------------------------------Economic Cost-------------------------------------------|-------- Director Estimate-----| $4,000 $3,322 $3,500 $3,000 $2,500 Average Cost Per Client-Episode of Care $1,984 $2,000 $1,559 $1,413 $1,500 $1,197 $1,126 $1,000 $500 $- ACRA (12.8 weeks) MET/CBT5 (6.8 weeks) MET/CBT5 (6.5 weeks) MET/CBT12 (13.4 weeks) FSN (14.2 weeks w/family) MDFT(13.2 weeks w/family) Source: French et al., 2002
Implementation of Evaluation • Over 85% of eligible families agreed to participate • Quarterly follow-up of 94 to 98% of the adolescents from 3- to 12-months (88% all five interviews) • Long term follow-up completed on 90% at 30-months and 91% (of 116 subsample) at 42-months • Collateral interviews were obtained at intake, 3- and 6-months on over 92-100% of the adolescents interviewed • Urine test data were obtained at intake, 3, 6, 30 and 42 months 90-100% of the adolescents who were not incarcerated or interviewed by phone (85% or more of all adolescents). • Self report marijuana use largely in agreement with urine test at 30 months (13.8% false negative, kappa=.63) • 5 Treatment manuals drafted, field tested, revised, send out for field review, and finalized • Descriptive, outcome and economic analyses completed Source: Dennis et al, 2002, under review
Adolescent Cannabis Users in CYT were as or More Severe Than Those in TEDS* Source: Tims et al, 2002
Demographic Characteristics Source: Tims et al, 2002
Institutional Involvement Source: Tims et al, 2002
Patterns of Substance Use 100% 73% 80% 71% 60% 40% 17% 20% 9% 0% Weekly Alcohol Weekly Weekly Significant Time Tobacco Use Cannabis Use Use in Controlled Environment Source: Tims et al, 2002
Multiple Problems are the NORM Self-Reported in Past Year Source: Dennis et al, under review
Co-occurring Problems are Higher for those Self-Reporting Past Year Dependence Source: Tims et al., 2002 * p<.05
CYT Increased Days Abstinent and Percent in Recovery (no use or problems while in community) Source: Dennis et al., 2004
Similarity of Clinical Outcomes by Conditions Source: Dennis et al., 2004
ACRA did better than MET/CBT5, and both did better than MDFT MET/CBT5 and 12 did better than FSN Moderate to large differences in Cost-Effectiveness by Condition Source: Dennis et al., 2004
Treatment Outcome Difference between intake and average of all short term follow-ups (3-12) Long Term Stability Difference between average of short term follow-ups (3-12) and long term follow-up (30) Short Term Outcome Stability Difference between average of early (3-6) and latter (9-12) follow-up interviews Evaluating the Effects of Treatment Month Z-Score Source: Dennis et al, under review, forthcoming
Treatment Outcome: • Use reduced (-34%) • No Sig. Dif. by condition • Long Term Stability: • - Use increases (+64%) • No Sig. Dif. by condition Short Term Stability: - Outcomes stable (-1%) - No Sig. Dif. by condition Change in Substance Frequency Scale in CYT Trial 1: Incremental Arm Months from Intake Source: Dennis et al, forthcoming
Treatment Outcome: • Problems reduced (-46%) • Sig. Dif. by condition • (-50% vs. –33% vs. –51%) • Short Term Stability: • Further reductions (-25%) • No difference by condition • Long Term Stability: • Problems increase (+17%) • Sig. Dif. by condition • (+37% vs +10% vs +7%) Change in Number of Substance Problems in CYT Trial 1: Incremental Arm Months from Intake Source: Dennis et al, forthcoming
Treatment Outcome: • Use reduced (-35%) • No Sig. Dif. by condition • Short Term Stability: • Further reductions (-6%) • Sig. Dif. by condition • (+4% vs. –10% vs. –11%) • Long Term Stability: • - Outcomes stable (+20%) • No Sig. Dif. by condition Change in Substance Frequency Scale inCYT Trial 2: Alternative Arm Months from Intake Source: Dennis et al, forthcoming
Treatment Outcome: - Problems reduced (-43%) - No difference by condition • Long Term Stability: • Outcomes stable (+7%) • No Sig. Dif. by condition Short Term Stability: - Outcomes stable (-8%) - No Sig. Dif. by condition Change in Number of Substance Problems inCYT Trial 2: Alternative Arm Months from Intake Source: Dennis et al, forthcoming
Percent in Past Month Recovery (no use or problems while living in the community) Source: Dennis et al, forthcoming
Cumulative Recovery Pattern at 30 months:(The Majority Vacillate in and out of Recovery) Source: Dennis et al, forthcoming
Initially (months 6-12) suppressed by controlled environment, but similar at 30 months Adolescent’s different in their Relapse trajectories Source: Godley, et al, 2004
The effects of adolescent treatment are mediated by the extent to which they lead to actual changes in the recovery environment or peer group Environmental Factors are also the Major Predictors of Relapse AOD use in the home, homelessness, family problems, fighting, victimization, self help group participation, structure activities Peer AOD use, fighting, illegal activity, treatment, recovery, vocational activity Model Fit CFI=.97 to .99 RMSEA=.04 to .06 Source: Godley et al (2005)
Cost Per Person in Recovery at 12 and 30 Months After Intake by CYT Condition Stability of MET/CBT-5 findings mixed at 30 months MET/CBT-5, -12 and ACRA more cost effective at 12 months $6,437 $10,405 $24,725 $27,109 $8,257 $14,222 CPPR at 30 months** Integrated family therapy (MDFT) was more cost effective than adding it on top of treatment (FSN) at 30 months Trial 1 (n=299) Trial 2 (n=297) Cost Per Person in Recovery (CPPR) $30,000 $25,000 $20,000 $15,000 $10,000 $5,000 $0 MET/ CBT5 MET/ CBT12 FSNM MET/ CBT5 ACRA MDFT $3,958 $7,377 $15,116 $6,611 $4,460 $11,775 CPPR at 12 months* * P<.0001, Cohen’s f= 1.42 and 1.77 at 12 months ** P<.0001, Cohen’s f= 0.76 and 0.94 at 30 months Source: Dennis et al., under review; forthcoming
Reduction in Average Cost to Society in CYT Trial 1: Incremental Arm Includes the cost of CYT Treatment Reductions (-23%) in Average Cost to Society offset Treatment Costs within 12 months Further Reductions (-47%) occurred out to 30 months Source: French et al, 2004; forthcoming
Reduction in Average Cost to Society in CYT Trial 2: Alternative Arm Includes the cost of CYT Treatment Average Cost to Society goes up then down and does not offset Tx Costs within 12 months (+7%) Further Reductions occurred out to 30 months (-40%) Source: French et al, 2004; forthcoming
Average Cost to Society Varied More by Site than Condition UCHC, Farmington, CT (-24%, -44%) PAR, St. Petersburg, FL (-22%, -49%) CHS, Madison Co., IL (-8%, -51%) CHOP, Philadelphia, PA (+18%, -34%) Site differences larger than tx differences $6,000 $5,000 $4,000 $3,000 $2,000 $1,000 $0 0 3 6 9 12 15 18 21 24 27 30 Months from Intake Source: French et al, 2004; forthcoming
Reprise of Clinical Outcomes • Co-occurring problems were the norm and varied with substance use severity. • In Trial 1, FSN and MET/CBT5 were relatively more effective than MET/CBT12 in reducing substance abuse/dependence problems (treatment effect); With FSN doing better at holding its gains out to 30 months • In Trial 2, ACRA and MDFT were more effective than MET/CBT5 in reducing substance abuse/dependence problems (treatment effect) and short term stability on substance use; With ACRA and MDFT doing better at holding their gains out to 30 months. • These were not easily explained simply by dosage or level of family therapy and there was no evidence of iatrogenic effects of group therapy. • While more effective than many earlier outpatient treatments, 2/3rds of the CYT adolescents were still having problems 12 months latter, 4/5ths were still having problems 30 months latter.
Reprise of Economic Outcomes • There were considerable differences in the cost of providing each of the interventions. • MET/CBT-5, -12 and ACRA were the most cost effective at 12 months, though the stability of the MET/CBT findings were mixed at 30 months. • Reductions in Average Quarterly Cost to Society offset the cost of treatment within 12 months in trial 1 and with 30 months in trial 2. • At 12 months the MET/CBT5 intervention clearly had the highest rate of return. • By 30 months MET/CBT12, ACRA and MDFT were doing better and FSN was doing as well as MET/CBT in terms of costs to society. • Results of clinical outcomes, cost-effectiveness, and benefit cost were different – suggesting the importance of multiple perspectives
Effective Adolescent Treatment (EAT) Replication of MET/CBT 5 • Large scale replication of the CYT MET/CBT intervention in early intervention, school, detention and outpatient settings • Data from 22 of 36 grants: Bradley, Brown, Clayton,Curry, Davis, Dillon, Dodge, Kressler, Kincaid, Levine, Levy, Locario, Mason, Moore, Rajaee-Moore, Paull, Payton, Rezende, Taylor, Tims, Turner, Vincent • 857 Intake cases and 521 3 Month Follow-up from 22 sites (71% of those due, 82% of those out of window) • Outcome data matched to people with both intake and follow-up • Early, but already larger that CYT (n=202 from 4 sites)
Higher rates of Retention and Continuing Care Similar on engagement and satisfaction General Treatment Process Measures Better than CYT on initiation 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Initiated (within 14 Engaged Retained Continuing Care High Satisfaction (4+ session, 6+ weeks) (90+ days in index admission) (post 90 days) (TxSI>13.5) days) CYT EAT Source: CYT Final Data Set and EAT 8/04 data set
Consistent MET/CBT5 Content Across Sites Virtually Identical Implementation in CYT UCHC (n=48) PAR (n=54) CHS (n=42) CHOP (n=58) * Total MET/CBT5 (n=202) Source: CYT data
Treatment Content Matches CYT (S7g) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Direct Family External Total (3-6,9-10,19,99) (1,7-8,15) (2,11-14,16-17) (all) CYT (n=199) EAT (n=201) Source: CYT Final Data Set and EAT 8/04 data set
Top 10 Reasons Adolescents Gave to Quit 10. 52% AOD cause health problems for others 9. 53% don't want to embarrass your family 8. 55% concerned about health problems 7. 56% to improve my memory 6. 57% to feel in control of your life 5. 57% to keep close people from being upset 4. 59% to think more clearly 3. 60% to save money you would have spend on AOD 2. 63% to prove you are not addicted 1. 73% to show you can quit These reasons provide hooks for MET and counseling in general Source: EAT 8/04 data set
Not everyone has the same reasons • 7 of 10 the same in CYT (included above) • 10 of 10 for 15 to 17, male, white adolescents • 8 of 10 for other ages • Under 15 more likely to say known others with health problems (55%) or to have more energy (55%) • 18 to 20 more likely to say known others with health problems (61%) or legal problems (58%) • 7 of 10 for females, who were more likely than males to say • because AOD is less "cool" (55% vs. 23%) • so that hair and clothes won't smell (54% vs. 40%) • To receive special gift if you quit (51% vs. 10%) • to avoid leave social functions to use (49% vs. 28%)
Not everyone has the same reasons (continued) • 6 or more of 10 for other races • African Americans more likely to say because AOD use may shorten your life (65%) and to have more energy (62%) • Asians more likely to say to have more energy (60%), so you can get more things done (60%), and so your hair and clothes will not smell (60%) • Hispanics more likely to say to have more energy (60%), because AOD use may shorten your life (57%) and because you will be praised by people close to you (57%) • Native Americans more likely to say to have more energy (100%), so you can get more things done (100%), because you noticed AOD use was hurting your health (100%), you will like yourself better if you quit (90%), because of legal problems (90%), so your hair and clothes will not smell (90%) Hence the need for personalized feedback
Comparison of In-Treatment Outcomes Substance Frequency Scale (SFS) Substance Problem Scale (SPS) 1 0.5 0 Z-Score from CYT MET/CBT5 baseline -0.5 -1 Lower severity at intake, Similar reductions at 3 months -1.5 Intake 3 M Intake 3 M CYT (n=202) EAT (n=409) Source: CYT Final Data Set and EAT 8/04 data set
Less Severe at Intake Both Improve Comparison of In-Treatment Outcomes (continued) 100% 90% 80% 70% 60% 50% 40% 40% 29% 27% 30% 20% 10% 3% 0% Intake 3 Month Intake 3 Month CYT (n=202) EAT (n=407) Source: CYT Final Data Set and EAT 8/04 data set
Impact and Next Steps • Papers published on design, validation, characteristics, matching, clinical contrast, treatment manuals, therapist reactions, cost, 12 month outcomes, cost-effectiveness, benefit cost • Papers with main clinical and cost-effectiveness findings at 30 month findings being submitted this year. • Interventions being replicated as part of over four dozen studies currently or about to go into the field • 30 to 40,000 copies of each of the 5 manuals distributed to policy makers, providers, individual clinicians and training programs Source: Dennis et al, 2002, in press
Implications • The CYT interventions provide replicable models of brief (1.5 to 3 month) treatments that can be used to help the field maintain quality while expanding capacity. • While a good start, the CYT interventions were still not an adequate dose of treatment for the majority of adolescents. • The majority of adolescents continued to vacillate in and out of recovery after discharge from CYT. • More work needs to be done on providing a continuum of care, longer term engagement and on going recovery management.
Contact Information Michael L. Dennis, Ph.D., CYT Coordinating Center PI Lighthouse Institute, Chestnut Health Systems 720 West Chestnut, Bloomington, IL 61701 Phone: (309) 820-3805, Fax: (309) 829-4661 E-Mail: Mdennis@Chestnut.Org Manuals and Additional Information are Available at: CYT: www.chestnut.org/li/cyt/findings or www.chestnut.org/li/bookstore or www.chestnut.org/li/apss/csat/protocols NCADI: www.health.org/govpubs
CYT References Babor, T. F., Webb, C. P. M., Burleson, J. A., & Kaminer, Y. (2002). Subtypes for classifying adolescents with marijuana use disorders Construct validity and clinical implications. Addiction, 97(Suppl. 1), S58-S69. Buchan, B. J., Dennis, M. L., Tims, F. M., & Diamond, G. S. (2002). Cannabis use Consistency and validity of self report, on-site urine testing, and laboratory testing. Addiction, 97(Suppl. 1), S98-S108. Dennis, M.L., (2002). Treatment Research on Adolescents Drug and Alcohol Abuse: Despite Progress, Many Challenges Remain. Connections, May, 1-2,7, and Data from the OAS 1999 National Household Survey on Drug Abuse Dennis, M. L., Babor, T., Roebuck, M. C., & Donaldson, J. (2002). Changing the focus The case for recognizing and treating marijuana use disorders. Addiction, 97 (Suppl. 1), S4-S15. Dennis, M.L., Dawud-Noursi, S., Muck, R., & McDermeit, M. (2003). The need for developing and evaluating adolescent treatment models. In S.J. Stevens & A.R. Morral (Eds.), Adolescent substance abuse treatment in the United States: Exemplary Models from a National Evaluation Study (pp. 3-34). Binghamton, NY: Haworth Press and 1998 NHSDA. Dennis, M. L., Funk, R., Godley, S. H., Godley, M. D., & Waldron, H. (2004). Cross validation of the alcohol and cannabis use measures in the Global Appraisal of Individual Needs (GAIN) and Timeline Followback (TLFB; Form 90) among adolescents in substance abuse treatment. Addiction, 99(Suppl. 2), 125-133. Dennis, M. L., Godley, S. H., Diamond, G., Tims, F. M., Babor, T., Donaldson, J., Liddle, H., Titus, J. C., Kaminer, Y., Webb, C., Hamilton, N., & Funk, R. (2004). The Cannabis Youth Treatment (CYT) Study: Main Findings from Two Randomized Trials. Journal of Substance Abuse Treatment, in press Dennis, M. L., Godley, S. and Titus, J. (1999). Co-occurring psychiatric problems among adolescents: Variations by treatment, level of care and gender. TIE Communiqué (pp. 5-8 and 16). Rockville, MD: Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment. Dennis, M. L. and McGeary, K. A. (1999). Adolescent alcohol and marijuana treatment: Kids need it now. TIE Communiqué (pp. 10-12). Rockville, MD: Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment. Dennis, M. L., Titus, J. C., Diamond, G., Donaldson, J., Godley, S. H., Tims, F., Webb, C., Kaminer, Y., Babor, T., Roebeck, M. C., Godley, M. D., Hamilton, N., Liddle, H., Scott, C., & CYT Steering Committee. (2002). The Cannabis Youth Treatment (CYT) experiment Rationale, study design, and analysis plans. Addiction, 97, 16-34.. Dennis, M. L., Titus, J. C., White, M., Unsicker, J., & Hodgkins, D. (2003). Global Appraisal of Individual Needs (GAIN) Administration guide for the GAIN and related measures. (Version 5 ed.). Bloomington, IL Chestnut Health Systems. Retrieve from http//www.chestnut.org/li/gain Dennis, M.L., & White, M.K. (2003). The effectiveness of adolescent substance abuse treatment: a brief summary of studies through 2001, (prepared for Drug Strategies adolescent treatment handbook). Bloomington, IL: Chestnut Health Systems. [On line] Available at http://www.drugstrategies.org Dennis, M. L. and White, M. K. (2004). Predicting residential placement, relapse, and recidivism among adolescents with the GAIN. Poster presentation for SAMHSA's Center for Substance Abuse Treatment (CSAT) Adolescent Treatment Grantee Meeting; Feb 24; Baltimore, MD. 2004 Feb. Diamond, G., Leckrone, J., & Dennis, M. L. (In press). The Cannabis Youth Treatment study Clinical and empirical developments. In R. Roffman, & R. Stephens, (Eds.) Cannabis dependence Its nature, consequences, and treatment . Cambridge, UK Cambridge University Press.