Using the Balanced-Placebo Design for Parsing Nicotine Administration Effects

Transcription

1 Using the Balanced-Placebo Design for Parsing Nicotine Administration Effects Thomas H. Brandon, Ph.D. & Amanda M. Palmer, M.A. Moffitt Cancer Center University of South Florida Tampa, Florida, USA Global Forum on Nicotine June, 2018 Warsaw, Poland

2 Why do Smokers Use E- cigarettes? Reduced health risk Cost Avoiding smoking restrictions To quit or reduce smoking cigarettes Dawkins, Turner, Roberts, & Soar, 2013; Siegel, Tanwar, & Wood, 2011

3 RCTs with E-cigarettes for Smoking Cessation Conclusions from RCTs Bullen et al. (2013) - randomly assigned nicotine patches, nicotine e-cigarettes, and placebo e- cigarettes 1. Some evidence of e-cigarette efficacy for smoking cessation. No significant differences in quit rates Caponnetto et al. (2013) randomly assigned e- cigarettes 2. Minimal with 2 nicotine doses, effects. or placebo. A reduction in cigarettes smoked was observed across all groups, regardless of nicotine content

4 Something Other than Nicotine? Sensorimotor Aspects of Vaping It looks and feels like smoking Cognitive Outcome Expectancies

5 Expectancies Beliefs about the effects of executing a behavior. Expectancies influence the probability of executing the behavior and the perceived effects of the behavior Measured by self-report or experimental designs

6 Self-Reported Drug Expectancies Positive drug expectancies predict every stage of drug use: Initiation Progression Cessation Relapse Strongest literature in Alcohol (Goldman) and Tobacco (Brandon)

7 Smoking Expectancies Negative Affect Reduction Stimulation Health Risk Taste/Senorimotor Social Facilitation Weight Control Craving/Addiction Negative Physical Feelings Boredom Reduction Negative Social Impression Copeland, Brandon, & Quinn, 1995

8 Expectancies for E-Cigarettes Compared to cigarettes: Less harmful and addictive Better tasting and more satisfying Compared to NRT Better at craving reduction Copp, Collins, Dar, & Barrett, 2015; Harrell et. al 2015; Harrell, 2014; Hendricks, 2014; Piñeiro et al., 2016

9 Experimental Designs: The Placebo-ControlledStudy Balanced Design Experimental Designs Instructional Manipulation Pharmacologic Manipulation Receiving Drug Not Receiving Drug Drug True positive False Negative, Anti- Placebo No Drug False positive, Placebo True Negative

10 Balanced-Placebo Design First used with Alcohol (Marlatt, Demming, & Reid, 1973) Nicotine Gum (Gottlieb, Killen, Marlatt, & Taylor, 1987) Cigarettes (Juliano & Brandon, 2002)

11 Experimental Designs: The Balanced Placebo Design Instructional Manipulation Pharmacologic Manipulation Receiving Drug Not Receiving Drug Drug No Drug True positive False positive, Placebo False Negative, Anti- Placebo True Negative Subjective, psychosocial variables: E.g., aggression, perceived sexual arousal, craving Physical, objective variables: E.g., attention, balance, physiological sexual arousal

12 The Current Study: Aims 1. Use Balanced-Placebo Design to compare the roles Hypothesis: of e-cigarette nicotine delivery vs. nicotine Told expectancies Nicotine will produce upon reduction greater in: a. cravingto reduction smokethan Told No b. craving Nicotine, toreflecting vape influence of 2. Test other underlying outcome expectancies. variables. 3. Examine moderator variables.

13 Study Design Instructional Manipulation E-cigarette Content Receiving Nicotine Not Receiving Nicotine Nicotine True positive False Negative, Anti- Placebo Non-nicotine False positive, Placebo True Negative

14 Study Sample (N = 128) Inclusion Criteria >18 years old Daily e-cigarette users Must use nicotine solutions Must like tobacco, menthol, or fruit flavor Smoking history of at least 100 lifetime cigarettes History of smoking rate of at least 1 cigarette per day for at least 30 days Exclusion Criteria No current engagement in an e-cigarette cessation attempt Not currently pregnant, attempting to get pregnant, or nursing (by self-report) 52 were dual users

15 Demographics Smoking and Vaping History Vaping Expectancies (SCQ-A) Dependence (FTND, Penn ECDI) Baseline Pre Ad-lib Post Ad-lib Cravings for Cigarettes (QSU Urge) Cravings for E-cigarettes (QSU Urge) Affect (PANAS) Appetite (VAS) E-cigarette Reinforcement (mceq) Attention (RVIP) Nicotine Dosing Estimate

16 3-hours of smoking and vaping abstinence prior to session Phone Screening Qualification Consent and Qualification Randomization (stratified by gender, smoking status, flavor) Baseline Questionnaires Pre Ad-lib Questionnaires Drug: Nicotine Instruction: Nicotine Drug: Non-Nicotine Instruction: Nicotine Drug: Nicotine Instruction: Non-Nicotine Drug: Non-Nicotine Instruction: Non-Nicotine Ad-libitum Vaping Session Post Ad-lib Questionnaires Debriefing Note: All research staff with participant contact was blind to drug randomization

17 Ad-lib Session Participants were told that we were interested in how vapers react to using an e-cigarette Told: E-cigarette contains a nicotine solution or a 0mg/ml nicotine solution Participants were given 10 minutes to use the e- cigarette Must take at least 10 puffs

18 Apparatus ego LCD MEGA Volt, 1100 mah battery with an ego+ 2.8-Ohm, 510-style clearomizer 50% propylene glycol, 50% vegetable glycerin solution containing either 0mg/ml or 12 mg/ml nicotine Ramôa et al., 2015

19 Results Craving to Smoke Craving Reduction N = 52 Dual Users Instructional Set Told No Nicotine Told Nicotine p <.05 No Nicotine Nicotine Actual Nicotine Content

20 Results Craving to Vape Craving Reduction N = Instructional Set Told No Nicotine Told Nicotine Interaction p <.05 No Nicotine Nicotine Actual Nicotine Content

21 Conclusions Craving to smoke influenced by instructional set, not actual nicotine. Driven by expectancies rather than pharmacology. Consistent with BPD studies on cigarettes and NRT. Consistent with the 2 clinical trials (Bullen/Caponnetto) that found little nicotine effect of e-cigarettes. Therapeutic effect of vaping may derive, in part, from users cognitive expectancies.

22 Craving to vape influenced by synergy of nicotine delivery and instructional set. Relevant to maintenance of vaping both expectancies and nicotine may be important.

23 Limitations Nicotine delivery not verified E-cigs are inconsisent Blood nicotine levels would be needed Newer devices with better nicotine delivery might show drug effect

24 Smoking Cessation Implications Emerging evidence indicates efficacy of e- cigarettes for smoking cessation. Nicotine delivery may not be necessary to manage cravings. Sensorimotor + expectancies may suffice.

25 Published in May

26 Thank You Questions? This research was supported in part by funding from the University of South Florida, the National Institute on Drug Abuse grant R01 DA037961, and the Proteomics Core at the H. Lee Moffitt Cancer Center & Research Institute, a comprehensive cancer center designated by the National Cancer Institute (P30 CA076292). Dr. Brandon has received research support from Pfizer, Inc.

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28 Demographics

29 Estimated Nicotine (mg/ml) Nicotine Estimation Instructional Set Told No Nicotine Told Nicotine p <.001 p <.001 No Nicotine Nicotine Actual Nicotine Content

30 Other Outcome Variables Variable Drug Instruction Interaction Comment Enjoyment of Resp. Tract Sensation Psychological Reward <.05 True Negative Highest <.01 True Positive Highest Aversion Satisfaction Sustained Attention (RVIP Sensitivity) Appetite Positive Affect (PANAS) <.05 Nicotine > Placebo Negative Affect (PANAS)

31 Variable Gender X Drug. Among males only, nicotine Craving to Vape increased reward. Moderation Results Gender Smoking Status Dependence Cravings to Smoke <.05 Enjoyment of Resp. Tract Sensation Gender X Drug. Among females only, nicotine improved attention. Psychological Reward <.01 Aversion <.05 Satisfaction Sustained Attention (RVIP Sensitivity) <.05 Appetite <.05 Expectancies Positive Affect (PANAS) <.05 <.05 Negative Affect (PANAS) Dependence X Drug. Among those receiving nicotine, dependence associated with greater craving reduction. Gender X Drug. Among females only, nicotine Stress-reduction increased aversion. Gender X Drug crossover. Greatest Status appetitex Instruction. Among those expectancies X reduction among Among females dual told users no-nicotine, only, higher not receiving nicotine, no-nicotine expectancies instructions were males recevingdecreased nicotine. positive associated with less affect. decline in positive affect.