Appetitive startle modulation in the human laboratory predicts Cannabis craving in the natural environment
- 21 Downloads
Drug-related cues evoke craving and stimulate motivational systems in the brain. The acoustic startle reflex captures activation of these motivational processes and affords a unique measure of reactivity to drug cues.
This study examined the effects of cannabis-related cues on subjective and eye blink startle reactivity in the human laboratory and tested whether these effects predicted youth’s cue-elicited cannabis craving in the natural environment.
Participants were 55 frequent cannabis users, ages 16 to 24 years (M = 19.9, SD = 1.9; 55% male; 56% met criteria for cannabis dependence), who were recruited from a clinical trial to reduce cannabis use. Eye blink electromyographic activity was recorded in response to acoustic probes that elicited startle reactivity while participants viewed pleasant, unpleasant, neutral, and cannabis picture cues. Following the startle assessment, participants completed an ecological momentary assessment protocol that involved repeated assessments of cue-elicited craving in real time in their real-world environments.
Multilevel models included the presence or absence of visible cannabis cues in the natural environment, startle magnitude, and the cross-level interaction of cues by startle to test whether cue-modulated startle reactivity in the laboratory was associated with cue-elicited craving in the natural environment. Analyses showed that cannabis-related stimuli evoked an appetitive startle response pattern in the laboratory, and this effect was associated with increased cue-elicited craving in the natural environment, b = − 0.15, p = .022, 95% CI [− 0.28, − 0.02]. Pleasant stimuli also evoked an appetitive response pattern, but in this case, blunted response was associated with increased cue-elicited craving in the natural environment, b = 0.27, p < .001, 95% CI [0.12, 0.43].
Our findings support cue-modulated startle reactivity as an index of the phenotypic expression of cue-elicited cannabis craving.
KeywordsStartle response Cues Craving, Cannabis Youth
The National Institute on Drug Abuse (R01 DA026778) and the National Institute on Alcohol Abuse and Alcoholism (R01 AA007850, K08 AA025011, K23 AA024808) at the National Institutes of Health supported this work. The authors wish to thank Alexander Blanchard for his contribution to the data collection and database management supporting this work.
- Blumenthal TD, Cuthbert BN, Filion DL, Hackley S Lipp OV, Van Boxtel A (2005) Committee report: Guidelines for human startle eyeblink electromyographic studies. Psychophysiology 42(1):1–15. https://doi.org/10.1111/j.1469-8986.2005.00271.x
- Bradley, M. M., & Lang, P. J. (2000). Measuring emotion: behavior, feeling, and physiology. In R. D. Lane & L. Nadel (Eds.), Cognitive neuroscience of emotion (pp. 242–276). New York, NYGoogle Scholar
- Charboneau EJ, Dietrich MS, Park S, Cao A, Watkins TJ, Blackford JU et al (2013) Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: preliminary results. Psychiatry Res Neuroimaging 214(2):122–131. https://doi.org/10.1016/j.pscychresns.2013.06.005 CrossRefPubMedGoogle Scholar
- Cui Y, Robinson JD, Versace F, Lam CY, Minnix JA, Karam-Hage M, Cinciripini PM (2012) Differential cigarette-related startle cue reactivity among light, moderate, and heavy smokers. Addict Behav 37(8):885–889. https://doi.org/10.1016/j.addbeh.2012.02.003
- Gibbons RD, Hedeker D, DuToit S (2010) Advances in analysis of longitudinal data. Annu Rev Clin Psychol 6:79–107. https://doi.org/10.1146/annurev.clinpsy.032408.153550 CrossRefPubMedPubMedCentralGoogle Scholar
- Hjorthøj CR, Fohlmann A, Larsen A-M, Arendt M, Nordentoft M (2012) Correlations and agreement between delta-9-tetrahydrocannabinol (THC) in blood plasma and timeline follow-back (TLFB)-assisted self-reported use of cannabis of patients with cannabis use disorder and psychotic illness attending the CapOpus randomized clinical trial. Addiction 107(6):1123–1131. https://doi.org/10.1111/j.1360-0443.2011.03757.x CrossRefPubMedGoogle Scholar
- Johnston, L.D., O’Malley, P.M., Bachman, J.G., Schulenberg, J.E., 2013. Monitoring the future national results on drug use: 2012 Overview, Key Findings on Adolescent Drug Use. Institute for Social Research. The University of Michigan, Ann ArborGoogle Scholar
- Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P et al (1997) Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36(7):980–988. https://doi.org/10.1097/00004583-199707000-00021 CrossRefPubMedGoogle Scholar
- Lang, P. J., Bradley, M. M., & Cuthbert, B. N. (1999). International affective picture system (IAPS): instruction manual and affective ratings. The center for research in psychophysiology, University of FloridaGoogle Scholar
- Leménager T, Hill H, Reinhard I, Hoffmann S, Zimmermann US, Hermann D et al (2014) Association between alcohol-cue modulated startle reactions and drinking behaviour in alcohol dependent patients—results of the PREDICT study. Int J Psychophysiol 94(3):263–271. https://doi.org/10.1016/j.ijpsycho.2014.09.009 CrossRefPubMedGoogle Scholar
- Loeber S, Croissant B, Nakovics H, Zimmer A, Georgi A, Klein S, Diener C, Heinz A, Mann K, Flor H (2007) The startle reflex in alcohol-dependent patients: changes after cognitive-behavioral therapy and predictive validity for drinking behavior—a pilot study. Psychother Psychosom 76(6):385–390. https://doi.org/10.1159/000107567 CrossRefPubMedGoogle Scholar
- Meehan JC, Miranda R Jr (2013) Startle reflex and psychophysiology. Wiley-Blackwell Handb Addict Psychopharmacol:367–598Google Scholar
- Miranda R, Ray L, Blanchard A, Reynolds EK, Monti PM, Chun T, Justus A, Swift RM, Tidey J, Gwaltney CJ, Ramirez J (2014) Effects of naltrexone on adolescent alcohol cue reactivity and sensitivity: an initial randomized trial. Addict Biol 19(5):941–954. https://doi.org/10.1111/adb.12050 CrossRefPubMedGoogle Scholar
- Raudenbush SW, Bryk AS (2002) Hierarchical linear models: applications and data analysis methods, 2nd edn. Sage Publications, Inc., Thousand Oaks, CAGoogle Scholar
- Ray LA, Miranda R, Tidey JW, McGeary JE, MacKillop J, Gwaltney CJ et al (2010) Polymorphisms of the μ-opioid receptor and dopamine D(4) receptor genes and subjective responses to alcohol in the natural environment. J Abnorm Psychol 119(1):115–125. https://doi.org/10.1037/a0017550 CrossRefPubMedPubMedCentralGoogle Scholar
- SAS Institute Inc. (n.d.). SAS/STAT software. Cary, NC, USA.Google Scholar
- Sayette MA (2016) The role of craving in substance use disorders: theoretical and methodological issues. Ann Rev Clin Psychol 12(November 2015):407–433. https://doi.org/10.1146/annurev-clinpsy-021815-093351 CrossRefGoogle Scholar
- Shiffman S, Stone AA, Hufford MR (2008) Ecological momentary assessment. Ann Rev Clin Psychol 4(1):1–32. https://doi.org/10.1146/annurev.clinpsy.3.022806.091415 CrossRefGoogle Scholar
- Substance Abuse and Mental Health Services Administration. (2015). Behavioral health trends in the United States: results from the 2014 National Survey on Drug Use and Health. (HHS Pulication No. SMA 15–4927, NSDUH Series H-50. Google Scholar
- Versace F, Engelmann JM, Deweese MM, Robinson JD, Green CE, Lam CY et al (2017) Beyond cue reactivity: non-drug-related motivationally relevant stimuli are necessary to understand reactivity to drug-related cues. Nicotine Tob Res 19(6):663–669. https://doi.org/10.1093/ntr/ntx002 CrossRefPubMedGoogle Scholar