The use of virtual reality in craving assessment and cue-exposure therapy in substance use disorders

Antoine Hone-Blanchet, Tobias Wensing, Shirley Fecteau, Antoine Hone-Blanchet, Tobias Wensing, Shirley Fecteau

Abstract

Craving is recognized as an important diagnosis criterion for substance use disorders (SUDs) and a predictive factor of relapse. Various methods to study craving exist; however, suppressing craving to successfully promote abstinence remains an unmet clinical need in SUDs. One reason is that social and environmental contexts recalling drug and alcohol consumption in the everyday life of patients suffering from SUDs often initiate craving and provoke relapse. Current behavioral therapies for SUDs use the cue-exposure approach to suppress salience of social and environmental contexts that may induce craving. They facilitate learning and cognitive reinforcement of new behavior and entrain craving suppression in the presence of cues related to drug and alcohol consumption. Unfortunately, craving often overweighs behavioral training especially in real social and environmental contexts with peer pressure encouraging the use of substance, such as parties and bars. In this perspective, virtual reality (VR) is gaining interest in the development of cue-reactivity paradigms and practices new skills in treatment. VR enhances ecological validity of traditional craving-induction measurement. In this review, we discuss results from (1) studies using VR and alternative virtual agents in the induction of craving and (2) studies combining cue-exposure therapy with VR in the promotion of abstinence from drugs and alcohol use. They used virtual environments, displaying alcohol and drugs to SUD patients. Moreover, some environments included avatars. Hence, some studies have focused on the social interactions that are associated with drug-seeking behaviors and peer pressure. Findings indicate that VR can successfully increase craving. Studies combining cue-exposure therapy with virtual environment, however, reported mitigated success so far.

Keywords: avatars; craving; cue exposure; substance use disorders; virtual reality.

References

    1. Acker J., MacKillop J. (2013). Behavioral economic analysis of cue-elicited craving for tobacco: a virtual reality study. Nicotine Tob. Res. 15, 1409–1416.10.1093/ntr/nts341
    1. Addolorato G., Leggio L., Hopf F. W., Diana M., Bonci A. (2012). Novel therapeutic strategies for alcohol and drug addiction: focus on GABA, ion channels and transcranial magnetic stimulation. Neuropsychopharmacology 37, 163–177.10.1038/npp.2011.216
    1. Barak S., Liu F., Ben Hamida S., Yowell Q. V., Neasta J., Kharazia V., et al. (2013). Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse. Nat. Neurosci. 16, 1111–1117.10.1038/nn.3439
    1. Baumann S. B., Sayette M. A. (2006). Smoking cues in a virtual world provoke craving in cigarette smokers. Psychol. Addict. Behav. 20, 484–489.10.1037/0893-164X.20.4.484
    1. Bechara A. (2005). Decision making, impulse control and loss of willpower to resist drugs: a neurocognitive perspective. Nat. Neurosci. 8, 1458–1463.10.1038/nn1584
    1. Bonson K. R., Grant S. J., Contoreggi C. S., Links J. M., Metcalfe J., Weyl L., et al. (2002). Neural systems and cue-induced cocaine craving. Neuropsychopharmacology 26, 1–11.10.1016/S0893-133X(01)00371-2
    1. Bordnick P. S., Carter B. L., Traylor A. C. (2011). What virtual reality research in addictions can tell us about the future of obesity assessment and treatment. J. Diabetes Sci. Technol. 5, 265–271.10.1177/193229681100500210
    1. Bordnick P. S., Copp H. L., Traylor A., Graap K. M., Carter B. L., Walton A., et al. (2009). Reactivity to cannabis cues in virtual reality environments. J. Psychoactive Drugs 41, 105–112.10.1080/02791072.2009.10399903
    1. Bordnick P. S., Graap K. M., Copp H., Brooks J., Ferrer M., Logue B. (2004). Utilizing virtual reality to standardize nicotine craving research: a pilot study. Addict. Behav. 29, 1889–1894.10.1016/j.addbeh.2004.06.008
    1. Bordnick P. S., Graap K. M., Copp H. L., Brooks J., Ferrer M. (2005). Virtual reality cue reactivity assessment in cigarette smokers. Cyberpsychol. Behav. 8, 487–493.10.1089/cpb.2005.8.487
    1. Bordnick P. S., Traylor A., Copp H. L., Graap K. M., Carter B., Ferrer M., et al. (2008). Assessing reactivity to virtual reality alcohol based cues. Addict. Behav. 33, 743–756.10.1016/j.addbeh.2007.12.010
    1. Brody A. L., Mandelkern M. A., London E. D., Childress A. R., Lee G. S., Bota R. G., et al. (2002). Brain metabolic changes during cigarette craving. Arch. Gen. Psychiatry 59, 1162–1172.10.1001/archpsyc.59.12.1162
    1. Brody A. L., Mandelkern M. A., Olmstead R. E., Jou J. (2007). Neural substrates of resisting craving during cigarette cue exposure. Biol. Psychiatry 62, 642–651.10.1016/j.biopsych.2006.10.026
    1. Bush J. (2008). Viability of virtual reality exposure therapy as a treatment alternative. Comput. Human Behav. 24, 1032–1040.10.1016/j.chb.2007.03.006
    1. Carter B. L., Bordnick P., Traylor A., Day S. X., Paris M. (2008). Location and longing: the nicotine craving experience in virtual reality. Drug Alcohol Depend. 95, 73–80.10.1016/j.drugalcdep.2007.12.010
    1. Carter B. L., Tiffany S. T. (2001). The cue-availability paradigm: the effects of cigarette availability on cue reactivity in smokers. Exp. Clin. Psychopharmacol. 9, 183–190.10.1037/1064-1297.9.2.183
    1. Cho S., Ku J., Park J., Han K., Lee H., Choi Y. K., et al. (2008). Development and verification of an alcohol craving-induction tool using virtual reality: craving characteristics in social pressure situation. Cyberpsychol. Behav. 11, 302–309.10.1089/cpb.2007.0149
    1. Choi J.-S., Park S., Lee J.-Y., Jung H.-Y., Lee H.-W., Jin C.-H., et al. (2011). The effect of repeated virtual nicotine cue exposure therapy on the psychophysiological responses: a preliminary study. Psychiatry Investig. 8, 155.10.4306/pi.2011.8.2.155
    1. Conklin C. A. (2006). Environments as cues to smoke: implications for human extinction-based research and treatment. Exp. Clin. Psychopharmacol. 14, 12–19.10.1037/1064-1297.14.1.12
    1. Conklin C. A., Parzynski C. S., Salkeld R. P., Perkins K. A., Fonte C. A. (2012). Cue reactivity as a predictor of successful abstinence initiation among adult smokers. Exp. Clin. Psychopharmacol. 20, 473–478.10.1037/a0029599
    1. Conklin C. A., Robin N., Perkins K. A., Salkeld R. P., McClernon F. J. (2008). Proximal versus distal cues to smoke: the effects of environments on smokers’ cue-reactivity. Exp. Clin. Psychopharmacol. 16, 207–214.10.1037/1064-1297.16.3.207
    1. Conklin C. A., Tiffanny S. T. (2002). Applying extinction research and theory to cue-exposure addiction treatments. Addiction 97, 155–167.10.1046/j.1360-0443.2002.00014.x
    1. Culbertson C., Nicolas S., Zaharovits I., London E. D., De La Garza R., II, Brody A. L., et al. (2010). Methamphetamine craving induced in an online virtual reality environment. Pharmacol. Biochem. Behav. 96, 454–460.10.1016/j.pbb.2010.07.005
    1. da Costa R. T., Sardinha A., Nardi A. E. (2008). Virtual reality exposure in the treatment of fear of flying. Aviat. Space Environ. Med. 79, 899–903.10.3357/ASEM.2277.2008
    1. De Leo G., Diggs L. A., Radici E., Mastaglio T. W. (2014). Measuring sense of presence and user characteristics to predict effective training in an online simulated virtual environment. Simul. Healthc. 9, 1–6.10.1097/SIH.0b013e3182a99dd9
    1. Drummond D. C., Cooper T., Glautier S. P. (1990). Conditioned learning in alcohol dependence: implications for cue exposure treatment. Br. J. Addict. 85, 725–743.10.1111/j.1360-0443.1990.tb01685.x
    1. Drummond D. C., Glautier S. P. (1994). A controlled trial of cue exposure treatment in alcohol dependence. J. Consult. Clin. Psychol. 62, 809–817.10.1037/0022-006X.62.4.809
    1. Feil J., Sheppard D., Fitzgerald P. B., Yücel M., Lubman D. I., Bradshaw J. L. (2010). Neuroscience and biobehavioral reviews. Neurosci. Biobehav. Rev. 35, 248–275.10.1016/j.neubiorev.2010.03.001
    1. Ferguson S. G., Shiffman S. (2009). The relevance and treatment of cue-induced cravings in tobacco dependence. J. Subst. Abuse Treat. 36, 235–243.10.1016/j.jsat.2008.06.005
    1. Ferrer-García M., Garcia M., Gutiérrez-Maldonado J., Pericot-Valverde I., Secades-Villa R. (2010). Efficacy of virtual reality in trigerring the craving to smoke: its relation to level of presence and nicotine dependence. Stud. Health Technol. Inform. 154, 123–127.10.3233/978-1-60750-561-7-123
    1. Ferrer-García M., Gutiérrez-Maldonado J., Pla J. (2013). Cue-elicited anxiety and craving for food using virtual reality scenarios. Stud. Health Technol. Inform. 191, 105–109.10.3233/978-1-60750-561-7-123
    1. Filbey F. M., Schatt J. P., Myers U. S., Chavez R. S., Hutchison K. E. (2009). Marijuana craving in the brain. Proc. Natl. Acad. Sci. U.S.A. 106, 13016–13021.10.1073/pnas.0903863106
    1. Franklin T. R., Wang Z., Wang J., Sciortino N., Harper D., Li Y., et al. (2007). Limbic activation to cigarette smoking cues independent of nicotine withdrawal: a perfusion fMRI study. Neuropsychopharmacology 32, 2301–2309.10.1038/sj.npp.1301371
    1. Galloway G. P., Singleton E. G. (2009). How long does craving predict use of methamphetamine? Assessment of use one to seven weeks after the assessment of craving: craving and ongoing methamphetamine use. Subst. Abuse 26, 63–79. Available at:
    1. Gamito P., Oliveira J., Baptista A., Pereira E., Morais D., Saraiva T., et al. (2011). Virtual reality exposure on nicotine craving. Stud. Health Technol. Inform. 167, 63–68.10.3233/978-1-60750-766-6-63
    1. Garavan H., Pankiewicz J., Bloom A., Cho J. K., Sperry L., Ross T. J., et al. (2000). Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli. Am. J. Psychiatry 157, 1789–1798.10.1176/appi.ajp.157.11.1789
    1. Garavan H., Stout J. C. (2005). Neurocognitive insights into substance abuse. Trends Cogn. Sci. (Regul. Ed.) 9, 195–201.10.1016/j.tics.2005.02.008
    1. Garcìa-Rodrìguez O., Pericot-Valverde I., Gutiérrez-Maldonado J., Ferrer-García M., Secades-Villa R. (2012). Validation of smoking-related virtual environments for cue exposure therapy. Addict. Behav. 37, 703–708.10.1016/j.addbeh.2012.02.013
    1. Garcìa-Rodrìguez O., Weidberg S., Gutiérrez-Maldonado J., Secades-Villa R. (2013). Smoking a virtual cigarette increases craving among smokers. Addict. Behav. 38, 2551–2554.10.1016/j.addbeh.2013.05.007
    1. Goldstein R. Z., Volkow N. D. (2002). Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am. J. Psychiatry 159, 1642–1652.10.1176/appi.ajp.159.10.1642
    1. Gonçalves R., Pedrozo A. L., Coutinho E. S., Figueira I., Ventura P. (2012). Efficacy of virtual reality exposure therapy in the treatment of PTSD: a systematic review. PLoS One 7:e48469.10.1371/journal.pone.0048469
    1. Havermans R. C., Jansen A. T. (2003). Increasing the efficacy of cue exposure treatment in preventing relapse of addictive behavior. Addict. Behav. 28, 989–994.10.1016/S0306-4603(01)00289-1
    1. Hofmann S. G., Meuret A. E., Smits J. A., Simon N. M., Pollack M. H., Eiseimenger K., et al. (2006). Augmentation of exposure therapy with d-cycloserine for social anxiety disorder. Arch. Gen. Psychiatry 63, 298–304.10.1001/archpsyc.63.3.298
    1. Hone-Blanchet A., Fecteau S. (2014). Overlap of food addiction and substance use disorders definitions: analysis of animal and human studies. Neuropharmacology 85, 81–90.10.1016/j.neuropharm.2014.05.019
    1. Jentsch J. D., Pennington Z. T. (2013). Reward, interrupted: inhibitory control and its relevance to addictions. Neuropharmacology 76(Pt B), 479–486.10.1016/j.neuropharm.2013.05.022
    1. Kaplan G. B., Heinrichs S. C., Carey R. J. (2011). Pharmacology, biochemistry and behavior. Pharmacol. Biochem. Behav. 97, 619–625.10.1016/j.pbb.2010.08.004
    1. Kennedy R. S., Lane N. E., Berbaum K. S., Lilienthal M. G. (1993). Simulator sickness questionnaire: an enhanced method for quantifying simulator sickness. Int. J. Aviat. Psychol. 3, 203–220.10.1207/s15327108ijap0303_3
    1. Kiryu T., So R. H. (2007). Sensation of presence and cybersickness in applications of virtual reality for advanced rehabilitation. J. Neuroeng. Rehabil. 4, 34.10.1186/1743-0003-4-34
    1. Kober H., Mende-Siedlecki P. (2010). Prefrontal-striatal pathway underlies cognitive regulation of craving. Proc. Natl. Acad. Sci. U.S.A. 107, 14811–14816.10.1073/pnas.1007779107
    1. Koechl B., Unger A., Fischer G. (2012). Age-related aspects of addiction. Gerontology 58, 540–544.10.1159/000339095
    1. Koob G., Volkow N. D. (2009). Neurocircuitry of addiction. Neuropsychopharmacology 35, 217–238.10.1038/npp.2009.110
    1. Kühn S., Gallinat J. (2011). Common biology of craving across legal and illegal drugs – a quantitative meta-analysis of cue-reactivity brain response. Eur. J. Neurosci. 33, 1318–1326.10.1111/j.1460-9568.2010.07590.x
    1. Kuntze M. F., Stoermer R., Mager R., Roessler A., Mueller-Spahn F., Bullinger A. H. (2001). Immersive virtual environments in cue exposure. Cyberpsychol. Behav. 4, 497–502.10.1089/109493101750527051
    1. Ledoux T., Nguyen A. S., Bakos-Block C., Bordnick P. (2013). Using virtual reality to study food cravings. Appetite 71, 396–402.10.1016/j.appet.2013.09.006
    1. Lee J., Lim Y., Graham S. J., Kim G., Wiederhold B. K., Wiederhold M. D., et al. (2004). Nicotine craving and cue exposure therapy by using virtual environments. Cyberpsychol. Behav. 7, 705–713.10.1089/cpb.2004.7.705
    1. Lee J.-H., Ku J., Kim K., Kim B., Kim I. Y., Yang B.-H., et al. (2003). Experimental application of virtual reality for nicotine craving through cue exposure. Cyberpsychol. Behav. 3, 275–281.10.1089/109493103322011560
    1. Lee J.-H., Lim Y., Wiederhold B. K., Graham S. J. (2005). A functional magnetic resonance imaging (fMRI) study of cue-induced smoking craving in virtual environments. Appl. Psychophysiol. Biofeedback 30, 195–204.10.1007/s10484-005-6377-z
    1. Lee J. S., Namkoong K., Ku J., Cho S., Park J. Y., Choi Y. K., et al. (2008). Social pressure-induced craving in patients with alcohol dependence: application of virtual reality to coping skill training. Psychiatry Investig. 5, 239–243.10.4306/pi.2008.5.4.239
    1. Lee S. H., Han D. H., Oh S., Lyoo I. K., Lee Y. S., Renshaw P. F., et al. (2009). Quantitative electroencephalographic (qEEG) correlates of craving during virtual reality therapy in alcohol-dependent patients. Pharmacol. Biochem. Behav. 91, 393–397.10.1016/j.pbb.2008.08.014
    1. Leeman R. F., Potenza M. N. (2011). Similarities and differences between pathological gambling and substance use disorders: a focus on impulsivity and compulsivity. Psychopharmacology 219, 469–490.10.1007/s00213-011-2550-7
    1. Lejuez C. W., Aklin W. M., Jones H. A., Richards J. B., Strong D. R., Kahler C. W., et al. (2003). The balloon analogue risk task (BART) differentiates smokers and nonsmokers. Exp. Clin. Psychopharmacol. 11, 26–33.10.1037/1064-1297.11.1.26
    1. Lim S., Reeves B. (2009). Computer agents versus avatars: responses to interactive game characters controlled by a computer or other player. J. Hum. Comput. Stud. 68, 57–68.10.1016/j.ijhcs.2009.09.008
    1. Lombard M., Ditton T. B., Weinstein L. (2009). “Measuring presence: the temple presence inventory,” in Proceedings of the 12th Annual International Workshop on Presence, Temple University, 1–15
    1. Maltby N., Kirsch I., Mayers M., Allen G. J. (2002). Virtual reality exposure therapy for the treatment of fear of flying: a controlled investigation. J. Consult. Clin. Psychol. 70, 1112–1118.10.1037/0022-006X.70.5.1112
    1. Mann K., Hermann D. (2010). Individualised treatment in alcohol-dependent patients. Eur. Arch. Psychiatry Clin. Neurosci. 260, 116–120.10.1007/s00406-010-0153-7
    1. Marshall J. F., O’Dell S. J. (2012). Methamphetamine influences on brainand behavior: unsafe at any speed? Trends Neurosci. 35, 536–545.10.1016/j.tins.2012.05.006
    1. Martin T., LaRowe S., Malcolm R. (2010). Progress in cue exposure therapy for the treatment of addictive disorders: a review update. Open Addict. J. 3, 92–101.10.2174/1874941001003020092
    1. McBride D., Barrett S. P., Kelly J. T., Aw A., Dagher A. (2006). Effects of expectancy and abstinence on the neural response to smoking cues in cigarette smokers: an fMRI study. Neuropsychopharmacology 31, 2728–2738.10.1038/sj.npp.1301075
    1. McClernon F. J., Kozink R. V., Lutz A. M., Rose J. E. (2008). 24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum. Psychopharmacology 204, 25–35.10.1007/s00213-008-1436-9
    1. Meyerbröker K., Emmelkamp P. M. (2010). Virtual reality exposure therapy in anxiety disorders: a systematic review of process-and-outcome studies. Depress. Anxiety 27, 933–944.10.1002/da.20734
    1. Moon J., Lee J. H. (2009). Cue exposure treatment in a virtual environment to reduce nicotine craving: a functional MRI study. Cyberpsychol. Behav. 12, 43–45.10.1089/cpb.2008.0032
    1. Myrick H., Anton R. F., Li X., Henderson S., Drobes D., Voronin K., et al. (2004). Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving. Neuropsychopharmacology 29, 393–402.10.1038/sj.npp.1300295
    1. National Institute on Drug Abuse. (2014). Trends and Statistics. Available at:
    1. Paliwal P., Hyman S. M., Sinha R. (2008). Craving predicts time to cocaine relapse: further validation of the now and brief versions of the cocaine craving questionnaire. Drug Alcohol Depend. 93, 252–259.10.1016/j.drugalcdep.2007.10.002
    1. Paris M. M., Carter B. L., Traylor A. C., Bordnick P. S., Day S. X., Armsworth M. W., et al. (2011). Cue reactivity in virtual reality: the role of context. Addict. Behav. 36, 696–699.10.1016/j.addbeh.2011.01.029
    1. Park C.-B., Choi J.-S., Park S. M., Lee J.-Y., Jung H.-Y., Seol J.-M., et al. (2014). Comparison of the effectiveness of virtual cue exposure therapy and cognitive behavioral therapy for nicotine dependence. Cyberpsychol. Behav. Soc. Netw. 17, 262–267.10.1089/cyber.2013.0253
    1. Pericot-Valverde I., Garcia M., Ferrer-García M., Secades-Villa R., Gutiérrez-Maldonado J. (2012). Virtual reality for smoking cessation: a case report. Stud. Health Technol. Inform. 181, 292–298.10.3233/978-1-61499-121-2-292
    1. Pericot-Valverde I., Garcia M., Gutiérrez-Maldonado J., Ferrer-García M., Secades-Villa R. (2011). Evolution of smoking urge during exposure through virtual reality. Stud. Health Technol. Inform. 167, 74–79.10.3233/978-1-60750-766-6-74
    1. Perkins K. A. (2012). Subjective reactivity to smoking cues as a predictor of quitting success. Nicotine Tob. Res. 14, 383–387.10.1093/ntr/ntr229
    1. Perry J. L., Joseph J. E., Jiang Y., Zimmerman R. S., Kelly T. H., Darna M., et al. (2011). Prefrontal cortex and drug abuse vulnerability: translation to prevention and treatment interventions. Brain Res. Rev. 64, 124–149.10.1016/j.brainresrev.2010.09.001
    1. Reger G. M., Gahm G. A. (2008). Virtual reality exposure therapy for active duty soldiers. J. Clin. Psychol. 64, 940–946.10.1002/jclp.20512
    1. Rose J. E. (2005). Nicotine and nonnicotine factors in cigarette addiction. Psychopharmacology 184, 274–285.10.1007/s00213-005-0250-x
    1. Ryan J. J., Kreiner D. S., Chapman M. D., Stark-Wroblewski K. (2010). Virtual reality cues for binge drinking in college students. Cyberpsychol. Behav. Soc. Netw. 13, 159–163.10.1089/cyber.2009.0211
    1. Saladin M. E., Brady K. T., Graap K., Rothbaum B. O. (2006). A preliminary report on the use of virtual reality technology to elicit craving and cue reactivity in cocaine dependent individuals. Addict. Behav. 31, 1881–1894.10.1016/j.addbeh.2006.01.004
    1. Schneider F., Habel U., Wagner M., Franke P., Salloum J. B., Shah N. J., et al. (2001). Subcortical correlates of cravingin recently abstinent alcoholic patients. Am. J. Psychiatry 158, 1075–1083.10.1176/appi.ajp.158.7.1075
    1. Seo D., Lacadie C. M., Tuit K., Hong K.-I., Constable R. T., Sinha R. (2013). Disrupted ventromedial prefrontal function, alcohol craving, and subsequent relapse risk. JAMA Psychiatry 70, 727–739.10.1001/jamapsychiatry.2013.762
    1. So R. H., Lo W. T., Ho A. T. (2001). Effects of navigation speed on motion sickness caused by an immersive virtual environment. Hum. Factors 43, 452–461.10.1518/001872001775898223
    1. Steketee J. D., Kalivas P. W. (2011). Drug wanting: behavioral sensitization and relapse to drug-seeking behavior. Pharmacol. Rev. 63, 348–365.10.1124/pr.109.001933
    1. Stoermer R., Mager R., Roessler A., Mueller-Spahn F., Bullinger A. H. (2000). Monitoring human-virtual reality interaction: a time series analysis approach. Cyberpsychol. Behav. 3, 401–407.10.1089/10949310050078850
    1. Tomasi D., Goldstein R. Z., Telang F., Maloney T., Alia-Klein N., Caparelli E. C., et al. (2007). Widespread disruption in brain activation patterns to a working memory task during cocaine abstinence. Brain Res. 1171, 83–92.10.1016/j.brainres.2007.06.102
    1. Traylor A. C., Bordnick P. S., Carter B. L. (2009). Using virtual reality to assess young adult smokers’ attention to cues. Cyberpsychol. Behav. 12, 373–378.10.1089/cpb.2009.0070
    1. Vögele C., Ehlers A., Meyer A. H., Frank M., Hahlweg K., Margraf J. (2010). Cognitive mediation of clinical improvement after intensive exposure therapy of agoraphobia and social phobia. Depress. Anxiety 27, 294–301.10.1002/da.20651
    1. Volkow N. D., Wang G.-J., Telang F., Fowler J. S., Logan J., Jayne M., et al. (2007). Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement. J. Neurosci. 27, 12700–12706.10.1523/JNEUROSCI.3371-07.2007
    1. Vollstädt-Klein S., Loeber S., Kirsch M., Bach P., Richter A., Bühler M., et al. (2011). Effects of cue-exposure treatment on neural cue reactivity in alcohol dependence: a randomized trial. Biol. Psychiatry 69, 1060–1066.10.1016/j.biopsych.2010.12.016
    1. Wang Z., Faith M., Patterson F., Tang K., Kerrin K., Wileyto E. P., et al. (2007). Neural substrates of abstinence-induced cigarette cravings in chronic smokers. J. Neurosci. 27, 14035–14040.10.1523/JNEUROSCI.2966-07.2007
    1. Watson N. L., Carpenter M. J., Saladin M. E., Gray K. M., Upadhyaya H. P. (2010). Addictive behaviors. Addict. Behav. 35, 673–677.10.1016/j.addbeh.2010.02.010
    1. World Health Organization. (2014). Management of Substance Abuse. Available at:
    1. Zilberman M. L., Tavares H., Blume S. B., El-Guebaly N. (2003). Substance use disorders: sex differences and psychiatric comorbidities. Can. J. Psychiatry 48, 5–14.

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