Modulation of Drug Craving in Crystalline-Heroin Users by Transcranial Direct Current Stimulation of Dorsolateral Prefrontal Cortex

Document Type : Original Article


1 PhD Candidate, Department of Health Psychology, School of Psychology, Karaj Branch, Islamic Azad University, Karaj AND Institute for Cognitive Science Studies, Brain and Cognition Clinic, Tehran, Iran

2 PhD Candidate, Department of Health Psychology, School of Psychology, Rudehen Branch, Islamic Azad University, Rudehen AND Institute for Cognitive Science Studies, Brain and Cognition Clinic, Tehran, Iran

3 Associate Professor, Department of Psychology, School of Social Sciences, Imam Khomeini International University, Qazvin, Iran

4 General Practitioner, Students Research Center of International Campus, Tehran University of Medical Sciences, Tehran, Iran

5 PhD Candidate, Department of Addiction Studies, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran

6 Assistant Professor, Department of Cognitive Rehabilitation, Institute for Cognitive Science Studies, Brain and Cognition Clinic, Tehran, Iran


Background: Drug craving, the main cause of relapse and a major motivator for drug use, is a challenging obstacle in substance use treatment. Transcranial direct current stimulation (tDCS), a non-invasive neuromodulatory technique, has shown promising outcomes in treating different neuropsychiatric disorders such as drug addiction, more specifically on drug craving. The aim in the current study was to examine the effects of applying tDCS on dorsolateral prefrontal cortex (DLPFC) in reducing drug cravings in former crystalline-heroin users enrolled in methadone maintenance (MMT) programs. Methods: The present study was a semi-experimental, crossover study with pre/post-test, and a control group. 40 right-handed men were selected from former crystalline-heroin users enrolled in MMT programs in Tehran, Iran. They were then divided into two matched groups based on age, education, and age of onset crystalline-heroin abuse. Desire for Drug Questionnaire (DDQ) was administered two times to all of the subjects, before first brain stimulation, and at the end of the last session. Experimental group received TDCS on DLPFC, and sham stimulation was applied on control subjects. The data were analyzed by analysis of covariance (ANCOVA) method using SPSS software. Findings: The study results indicated anodal tDCS over right and cathodal TDCS over left DLPFC, and in parallel with sham, significantly decreased drug cravings among former crystalline-heroin users (P < 0.050). Conclusion: This study showed that applying TDCS on DLPFC of former crystalline-heroin users reduces drug craving. The findings of this study expanded the results of previous studies on effects of this neuromodulatory technique for drug craving reduction in other drug type settings.


1. United Nations Office on Drugs and Crime. World drug report 2015 [Online]. [cited 2015]; Available from: URL:
2. Farhoudian A, Sadeghi M, Khoddami Vishteh HR, Moazen B, Fekri M, Rahimi Movaghar A. Component analysis of Iranian crack; A newly abused narcotic substance in Iran. Iran J Pharm Res 2014; 13(1): 337-44.
3. Hassani-Abharian P, Ganjgahi H, Tabatabaei-Jafari H, Oghabian MA, Mokri A, Ekhtiari H. Exploring neural correlates of different dimensions in drug craving self-reports among heroin dependents. Basic Clin Neurosci 2015; 6(4): 271-84.
4. Skinner MD, Aubin HJ. Craving's place in addiction theory: Contributions of the major models. Neurosci Biobehav Rev 2010; 34(4): 606-23.
5. Sofuoglu M, DeVito EE, Waters AJ, Carroll KM. Cognitive enhancement as a treatment for drug addictions. Neuropharmacology 2013; 64: 452-63.
6. Sinha R, Garcia M, Paliwal P, Kreek MJ, Rounsaville BJ. Stress-induced cocaine craving and
hypothalamic-pituitary-adrenal responses are predictive of cocaine relapse outcomes. Arch Gen Psychiatry 2006; 63(3): 324-31.
7. Shahbabaie A, Golesorkhi M, Zamanian B, Ebrahimpoor M, Keshvari F, Nejati V, et al. State dependent effect of transcranial direct current stimulation (tDCS) on methamphetamine craving. Int J Neuropsychopharmacol 2014; 17(10): 1591-8.
8. Shariatirad S, Vaziri A, Hassani-Abharian P, Sharifi FM, Molavi N, Fitzgerald PB. Cumulative and booster effects of tdcs sessions on drug cravings, lapse, and cognitive impairment in methamphetamine use disorder: A case study report. Am J Addict 2016; 25(4): 264-6.
9. Sharifi Fardshad M, Shams Esfandabad H, Hasani Abharian P. Assessment of the effect of transcranial direct current stimulation (tDCS) of dorsolateral prefrontal cortex on modulation of heroin crack craving. J Shahrekord Univ Med Sci 2016; 18(2): 109-21. [In Persian].
10. Chib VS, Yun K, Takahashi H, Shimojo S. Noninvasive remote activation of the ventral midbrain by transcranial direct current stimulation of prefrontal cortex. Transl Psychiatry 2013; 3: e268.
11. Jansen JM, Daams JG, Koeter MW, Veltman DJ, van den Brink W, Goudriaan AE. Effects of non-invasive neurostimulation on craving: A meta-analysis. Neurosci Biobehav Rev 2013; 37(10 Pt 2): 2472-80.
12. Moorman DE, Aston-Jones G. Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction. Proc Natl Acad Sci U S A 2015; 112(30): 9472-7.
13. Capriles N, Rodaros D, Sorge RE, Stewart J. A role for the prefrontal cortex in stress- and cocaine-induced reinstatement of cocaine seeking in rats. Psychopharmacology (Berl) 2003; 168(1-2): 66-74.
14. Lou M, Wang E, Shen Y, Wang J. Cue-elicited craving in heroin addicts at different abstinent time: An fMRI pilot study. Subst Use Misuse 2012; 47(6): 631-9.
15. Boggio PS, Sultani N, Fecteau S, Merabet L, Mecca T, Pascual-Leone A, et al. Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: A double-blind, sham-controlled study. Drug Alcohol Depend 2008; 92(1-3): 55-60.
16. da Silva MC, Conti CL, Klauss J, Alves LG, do Nascimento Cavalcante HM, Fregni F, et al. Behavioral effects of transcranial direct current stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence. J Physiol Paris 2013; 107(6): 493-502.
17. Goldman RL, Borckardt JJ, Frohman HA, O'Neil PM, Madan A, Campbell LK, et al. Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces food cravings and increases the self-reported ability to resist food in adults with frequent food craving. Appetite 2011; 56(3): 741-6.
18. Fregni F, Orsati F, Pedrosa W, Fecteau S, Tome FA, Nitsche MA, et al. Transcranial direct current stimulation of the prefrontal cortex modulates the desire for specific foods. Appetite 2008; 51(1): 34-41.
19. Kekic M, McClelland J, Campbell I, Nestler S, Rubia K, David AS, et al. The effects of prefrontal cortex transcranial direct current stimulation (tDCS) on food craving and temporal discounting in women with frequent food cravings. Appetite 2014; 78: 55-62.
20. Boggio PS, Liguori P, Sultani N, Rezende L, Fecteau S, Fregni F. Cumulative priming effects of cortical stimulation on smoking cue-induced craving. Neurosci Lett 2009; 463(1): 82-6.
21. Fregni F, Liguori P, Fecteau S, Nitsche MA, Pascual-Leone A, Boggio PS. Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: A randomized, sham-controlled study. J Clin Psychiatry 2008; 69(1): 32-40.
22. Boggio PS, Zaghi S, Villani AB, Fecteau S, Pascual-Leone A, Fregni F. Modulation of risk-taking in marijuana users by transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal
cortex (DLPFC). Drug Alcohol Depend 2010; 112(3): 220-5.
23. Hassani-Abharian P, Mokri A, Ganjgahi H, Oghabian MA, Ekhtiari H. Validation for Persian versions of "desire for drug questionnaire" and "obsessive compulsive drug use scale" in heroin dependents. Arch Iran Med 2016; 19(9): 659-65.
24. DaSilva AF, Volz MS, Bikson M, Fregni F. Electrode positioning and montage in transcranial direct current stimulation. J Vis Exp 2011; (51).
25. Maarefvand M, Safaeian S, Mokri A, Rezaei S, Daneshmnad R, Farhoudian A, et al. Clinical drug addiction profile (CDAP) questionnaire. Tehran, Iran: Mehrsa Publications; 2012. p. 1-64. [In Persian].
26. Conti CL, Nakamura-Palacios EM. Bilateral transcranial direct current stimulation over dorsolateral prefrontal cortex changes the drug-cued reactivity in the anterior cingulate cortex of crack-cocaine addicts. Brain Stimul 2014; 7(1): 130-2.
27. Fecteau S, Agosta S, Hone-Blanchet A, Fregni F, Boggio P, Ciraulo D, et al. Modulation of smoking and decision-making behaviors with transcranial direct current stimulation in tobacco smokers: A preliminary study. Drug Alcohol Depend 2014; 140: 78-84.
28. Diana M. The dopamine hypothesis of drug addiction and its potential therapeutic value. Front Psychiatry 2011; 2: 64.
29. Diana M, Spiga S, Acquas E. Persistent and reversible morphine withdrawal-induced morphological changes in the nucleus accumbens. Ann N Y Acad Sci 2006; 1074: 446-57.
30. George MS, Stallings LE, Speer AM, Nahas Z, Spicer KM, Vincent DJ. Prefrontal repetitive transcranial magnetic stimulation (rTMS) changes relative perfusion locally and remotely. Hum Psychopharmacol 1999; 14(3): 161-70.
31. Wanat MJ, Willuhn I, Clark JJ, Phillips PE. Phasic dopamine release in appetitive behaviors and drug addiction. Curr Drug Abuse Rev 2009; 2(2): 195-213.
32. Wilson SJ. The wiley handbook on the cognitive neuroscience of addiction. Hoboken, NJ: John Wiley & Sons; 2015.
33. Fecteau S, Knoch D, Fregni F, Sultani N, Boggio P, Pascual-Leone A. Diminishing risk-taking behavior by modulating activity in the prefrontal cortex: A direct current stimulation study. J Neurosci 2007; 27(46): 12500-5.
34. Feil J, Sheppard D, Fitzgerald PB, Yucel M, Lubman DI, Bradshaw JL. Addiction, compulsive drug seeking, and the role of frontostriatal mechanisms in regulating inhibitory control. Neurosci Biobehav Rev 2010; 35(2): 248-75.
35. Jauch-Chara K, Kistenmacher A, Herzog N, Schwarz M, Schweiger U, Oltmanns KM. Repetitive electric brain stimulation reduces food intake in humans. Am J Clin Nutr 2014; 100(4): 1003-9