Double Trouble: Tobacco And Marijuana, Treatment Development

Alan J. Budney, Ph.D.Addiction and Health Research

Department of Psychiatry Geisel School of Medicine at Dartmouth

2014 Norris Cotton Cancer Center Comprehensive Thoracic Oncology Program Retreat

May 22, 2014

Disclosures

Research supported by NIH (NIDA)• NIDA R01-DA032243

– (Targeting Tobacco and Cessation During Treatment for Cannabis Use Disorders)• NIDA R01-DA012471

– (Treatment of Adolescent Marijuana Use)• NIDA T32-DA037202

– (Science of Co-Occurring Disorders)

- Limited Consultation with GW Pharmaceuticals/Otsuka (2011)

- Participation in Pharmaceutical Company Trials (1995-2004)

Outline

• Prevalence of cannabis (marijuana) use and problematic use

• Prevalence of and concerns with co-use of tobacco and marijuana

• Clinical approaches to treatment• Current pilot study• Discussion

Past Month Illicit Drug Use among Persons Aged 12 or Older: 2012

SAMHSA, 2013

Dependence or Abuse on Specific Drugs in the Past Year Among Persons 12 or Older, (2012)

SAMHSA, 2013

Substances for Which Most Recent Treatment Was Received in the Past Year (Aged 12 or Older)

SAMHSA, 2013

Marijuana and Tobacco Co-UsePast Year Use  PrevalenceCannabis users reporting cigarette use 64.8%   Past Month  Cannabis users reporting cigarette use 60.5%   Dependence  Cannabis dependence with tobacco dependence 34%

Approximately 50% of adults in treatment for cannabis use disorders (CUD) report concurrent tobacco use

SAMHSA, 2013

Patterns of Co-Use

• Tobacco use onset has typically preceded marijuana use; but not always and some indication that this trend is changing

• Smoked together (blunts, spliffs, vapor pens or pipes)

• Chasing: smoke a cigarette immediately after marijuana• Separately: smoke marijuana, use tobacco as usual, no

intentional mixing

The Future??

Mechanisms Underlying Co-Use?

–Common and reciprocal genetic pathways to co-use• Evidence from twin studies suggests heritability

• CNR1 polymorphism associated with nicotine dependence

–Pharmacological interactions (increase reinforcing effects)• Endocannabinoid system is involved in the reinforcing effects

of nicotine• Marijuana users report tobacco use enhances the marijuana

high

Mechanisms Underlying Co-Use?

• Common route of administration– both substances typically inhaled by smoking

(vaporizing)– may increase learned associations between substances

through conditioned smoking cues signaling availability of reinforcement from the other substance

• Understanding neurobiological or behavioral mechanisms underlying co-use may improve treatments

Concerns of Co-Use

- Social, psychological, and physical impairments related to use

- Substantial public-health costs due to tobacco-related illnesses and death

- Targeting only cannabis still leaves the substantial negative-health related consequences of tobacco use

- Co-use Impacts Treatment Outcomes

- Use of one can negatively impact quit rates for the other

- Tobacco smoking is a predictor of poor outcomes for those in treatment for cannabis use disorders

- Cannabis use among tobacco smokers predicts continued long term tobacco use

Cannabis and Respiratory System and Cancer RiskGates et al. (2014)

• Why should we be concerned– Cannabis smoke contains similar array of carcinogens to

tobacco smoke (e.g. increased tar, ammonia, hydrogen cyanide)

– Smoking topography: prolonged and deep inhalation• 5-fold increase in carboxyhemoglobin• 4-fold increase in tar inhaled; 30% more retention in lower airway

– Quantity, frequency, and duration of use are associated with respiratory problems

– A lot we don’t know: dose effects, impact of different cannabinoids (e.g., CBD)

– Data are not clear that it has additive effects to tobacco

Cannabis and Respiratory System and Cancer Risk

– Bronchial dynamics (acute effect: bronchodialator)– Results in airway inflammation and infection

• Increased bronchitis and seeking of Rx for respiratory illness• Higher frequency cough, sputem production, and wheezing

– Equivocal data on COPD and related indicatior (FEV, FCV) and Emphysema (sparse literature)

– Lung Cancer• Some support for a link between cannabis use and

cancer risk, but • Suggest link between use and premalignant cancer• Link to development of lung cancer remains weak

– Link to “heavy” use more positive

Treatment for Cannabis Use Disorder

• Effective behavioral treatments for CUD: • Gold Standard: Combination of Cognitive

Behavioral Therapy (CBT) and Contingency Management (CM)

Typical Program

- 12 Weeks

- Weekly Counseling Sessions

- Abstinence-based Incentives

Motivational Incentives (CM) Improve Outcome

0

10

20

30

40

50

ETX 3 6 9 12

Months Post Treatment

% o

f P

arti

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nts

Abs

tine

nt

MET/CBT MET/CBT/CM CM

Budney et al. (2006)

Computer-Assisted Treatment P

erce

nta

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f P

arti

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ants

Budney et al. (in prep)

What about Tobacco in this Population? • Tobacco users (50%) have poorer outcomes• Almost none quit tobacco during treatment • Negative health consequences of tobacco use

Suggested that targeting tobacco use might be an option for increasing treatment success and reducing harm from tobacco

• Approaches for integrating treatments– sequential (cannabis treatment first, then offer

treatment for tobacco) – simultaneous (treat both at the same time)

Potential Approaches to Combining Interventions

Tobacco Intervention

• Combination behavioral counseling (computer-assisted) and pharmacotherapy

• NRT was chosen over other pharmacotherapies for tobacco two reasons: 1) varenicline and bupropion have side effects profiles that

may increase symptoms of cannabis withdrawal

2) NRT is available without a prescription; easier to access

We provide Patch, Gum, Lozenges

NIDA R01

• Aims

– develop and pilot test a treatment program providing an intervention for tobacco during treatment for CUD

– conduct an initial randomized trial

Cannabis MET/CBT Computer Modules• Modules 1 and 2 (MET)

– an interactive review of a personalized feedback report– goal-setting exercises, including setting a quit date

• Modules 3–8 (CBT)– developing an effective social support system, – understanding use patterns, – coping with craving, managing thoughts about using, – problem solving, – refusal skills, – coping with lapses, – managing moods, – assertiveness skills, – lifestyle goal-setting exercise.

• The last module encourages participants to revisit helpful computer modules, and to remotely access the relapse prevention module in the future.

Tobacco Intervention

5 computer modules (10-30 min each)– personalized assessment - Stop Tabac (Etter, 2009)

– Psychoeducation: co-use of cannabis and tobacco – NRT education and instruction; – planning for change/setting a quit date; – reduction strategies

Sample of a cumulative progress graph (i.e. cumulative weeks negative cannabis urine screens)

Stop Tobacco: Personalized Feedback Report

Email Messages

Intended to motivate and provide specific instructions based upon responses to the personalized questionnaire

Participants

• Inclusion Criteria:– adult (> 18 years old) cannabis users seeking

treatment for cannabis who also smoke tobacco regularly

– meet DSM-IV diagnosis for cannabis abuse or dependence

– at least some interest in quitting tobacco (> 2 on a 5 pt scale)

Participant DemographicsDemographic Mean (SD)

N 14 enrolled

Age 35.4 (14.1)

Gender 12 Male/2 Female

Drug Use History Mean (SD)

Age of Initiation

Cannabis 15.7 (3.3)

Tobacco 15.0 (3.3

Prior Quit Attempts

Cannabis 3.6 (4.0)

Tobacco 3.5 (3.6)

Tobacco Dependence (FTND) 3.0 (2.4)

Drug Use (past 90 days) Mean (SD)

Cannabis occasions per day 3.2 (1.2) 85/90 days

Tobacco cigarettes per day 11.2 (8.2) 83/90 days

Pilot Study Hypotheses1) 90% would complete the first tobacco module.

2) >40% would set tobacco smoking quit dates and initiate NRT.

3) Tobacco quit attempts: >35% would make at least one tobacco quit attempt (>24 hrs);>25–30% would achieve two weeks of continuous abstinence;>15–25% would be tobacco abstinent during the final 4–6 weeks.

4) <10% would report adverse effects of NRT that led to discontinuation.

5) >35–40% would achieve >4 weeks of documented continuous cannabis abstinence during treatment.

Summary of Outcomes1) 12 out of 14 participants completed at least one tobacco module

(mean = 2.2 modules).

2) 3 out of 14 participants set a quit date, and 8 out of 14 initiated NRT.

3) Tobacco quit attempts:10 of 14 made at least one quit attempt lasting at least 24 hrs, 5 made quit attempts lasting at least two weeks, 1 was tobacco abstinent for the final four weeks of treatment.

4) No participant discontinued NRT use due to adverse effects.

5) 6 out of 14 participants achieved >4 weeks of documented continuous cannabis abstinence (mean = 9.5 weeks)

Cannabis and Tobacco Outcomes

Cannabis and Tobacco Outcomes

Cannabis and Tobacco Outcomes

Summary• Preliminary fidnings from the pilot:

– the tobacco intervention is not adversely impacting cannabis outcomes;

– the majority participated in the tobacco intervention and showed substantial interest in quitting or reducing

– sustained tobacco quit rates are lower than anticipated, but participants are reducing use and attempting to quit tobacco

Alternative Strategies

• Decision Support System Task (Mary Brunette, M.D.)– web-based interactive assessment

• Subsequent incentive program for tobacco abstinence – Add an 8-week incentive program targeting both for those

who quit cannabis but not tobacco

• Increase utilization of Stop Tabac (i.e. encourage use of supportive emails, setting a quit date)

• Additional pharmacological options (i.e. varenicline, buproprion)

Final Comments

• Marijuana use is likely to increase• Higher potency marijuana will be used• Combined nicotine/tobacco/cannabis products will be

developed and marketed• May become gateway for tobacco / nicotine• Vaporizers / e-cigs e-pens / will have impact on

prevalence of use and co-use....consequences are unclear

• How all this will impact your field.....IDK

Acknowledgements

Co-Investigators• Dustin Lee, Ph.D.• Catherine Stanger, Ph.D.• Mary Brunette, M.D.• John Hughes, M.D.• Jean-Francois Etter, Ph.D.

Clinic Staff Members• Kathy Marshall, M.S.• Gray Norton, B.A.• Stanley See, B.S.• Hao Yang, B.S.• William Pelham III

Funding: National Institute on Drug Abuse: R01 DA032243

Thank you for your attention!

Questions?