Skip to main content

Advertisement

Log in

A pilot study of the effectiveness of d-cycloserine during cue-exposure therapy in abstinent alcohol-dependent subjects

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Cue-exposure therapy (CET) has been advocated as a potentially effective treatment of addictive behaviours. Strategies that enhance learning may improve the outcome of CET. d-cycloserine (DCS), a partial N-methyl-d-aspartate receptor agonist, has been shown to facilitate extinction of learned fear in rats and augment exposure-based treatment in some anxiety disorders in man.

Objective

This double-blind placebo-controlled pilot study used a cue-exposure paradigm, salient for an individual’s alcohol drinking, to see if DCS would reduce cue-reactivity compared with placebo.

Methods

Sixteen abstinent, alcohol-dependent individuals were randomised to receive either a single-dose (250 mg) DCS or placebo before CET sessions, separated by at least 1 week. Subjective responses were assessed using the Alcohol Urge Questionnaire (AUQ) and visual analogue scales. Cardiovascular responses were assessed using Finapres©.

Results

The cue-exposure paradigm significantly increased craving assessed with the AUQ during the first session. In subsequent sessions, the degree of craving was reduced. However, no significant difference was seen between the DCS and placebo groups in any outcome measure. The variability of responses between individuals was great with more than half the groups reporting no or very small changes in AUQ scores.

Conclusion

This is the first human study to our knowledge to assess the efficacy of DCS in facilitating CET in alcohol dependence. The high proportion of subjects with little or no response to cue-exposure would make any effect of DCS very difficult to detect. It is important that future studies carefully consider the criteria for inclusion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Anton R, Moak D, Latham P (1996) The obsessive compulsive drinking scale. A new method of assessing outcome in alcoholism treatment studies. Arch Gen Psychiatry 53:225–31

    PubMed  CAS  Google Scholar 

  • Beck A, Ward C, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–71

    PubMed  CAS  Google Scholar 

  • Bohn MJ, Krahn DD, Staehler BA (2005) Development and initial validation of a measure of drinking urges in abstinent alcoholics. Alcohol Clin Exp Res 19(3):600–6

    Google Scholar 

  • Cloninger CR, Przybeck TR, Svrakic DM (1991) The tridimensional personality questionnaire: U.S. normative data. Psychol Rep 69(3 Pt 1):1047–57

    Article  PubMed  CAS  Google Scholar 

  • Conklin CA, Tiffany ST (2002) Applying extinction research and theory to cue-exposure addiction treatments. Addiction 97(2):155–67

    Article  PubMed  Google Scholar 

  • Coupland NJ, Wilson SJ, Potokar JP, Bell CE, Bailey JE, Nutt DJ (1995) A comparison of the effects of phenelzine treatment with moclobemide treatment on cardiovascular reflexes. Int Clin Psychopharmacol 10:229–238

    Article  PubMed  CAS  Google Scholar 

  • Davis M, Ressler K, Rothbaum BO, Richardson R (2006) Effects of d-cycloserine on extinction: translation from preclinical to clinical work. Biol Psychiatry 60(4):369–75

    Article  PubMed  CAS  Google Scholar 

  • Drummond DC (2001) Theories of drug craving, ancient and modern. Addiction 96(1):33–46

    Article  PubMed  CAS  Google Scholar 

  • Drummond DC, Glautier S (1994) A controlled trial of cue exposure treatment in alcohol dependence. J Consult Clin Psychol 62(4):809–17

    Article  PubMed  CAS  Google Scholar 

  • Drummond DC, Tiffany ST, Glautier S, Remington B (1995) Cue exposure in understanding and treating addictive behaviours. In: Drummond DC, Tiffany ST, Glautier S, Remington B (eds) Addictive behaviours: cue exposure theory and practice. Wiley, London, pp 1–17

    Google Scholar 

  • Ehrman RN, Robbins SJ, Childress AR, Goehl L, Hole AV, O’Brien CP (1998) Laboratory exposure to cocaine cues does not increase cocaine use by outpatient subjects. J Subst Abuse Treat 15(5):431–5

    Article  PubMed  CAS  Google Scholar 

  • Eysenck HJ & Eysenck SBG. (1975) Manual of the Eysenck Personality Questionnaire. London, Hodder & Stoughton.

  • Eysenck SBG, Eysenck HJ, Barrett P (1985) A revised version of the psychoticism scale. Person Individ Difl 6(1):21–29

    Article  Google Scholar 

  • Guastella AJ, Richardson R, Lovibond PF et al (2008) A randomized controlled trial of d-cycloserine enhancement of exposure therapy for social anxiety disorder. Biol Psychiatry 63(6):544–9

    Article  PubMed  CAS  Google Scholar 

  • Hammersley R (1992) Cue exposure and learning theory. Addict Behav 17(3):297–300

    Article  PubMed  CAS  Google Scholar 

  • Heather N, Bradley BP (1990) Cue exposure as a practical treatment for addictive disorders: why are we waiting? Addict Behav 15(4):335–7

    Article  PubMed  CAS  Google Scholar 

  • Hofmann SG (2007) Enhancing exposure-based therapy from a translational research perspective. Behav Res Ther 45(9):1987–2001

    Article  PubMed  Google Scholar 

  • Hofmann SG, Meuret AE, Smits JA et al (2006a) Augmentation of exposure therapy for social anxiety disorder with d-cycloserine. Arch Gen Psychiatry 63:298–304

    Article  PubMed  CAS  Google Scholar 

  • Hofmann SG, Pollack MH, Otto MW (2006b) Augmentation treatment of psychotherapy for anxiety disorders with d-cycloserine. CNS Drug Rev 12(3–4):208–17

    Article  PubMed  CAS  Google Scholar 

  • Ledgerwood L, Richardson R, Cranney J (2003) Effects of d-cycloserine on extinction of conditioned freezing. Behav Neurosci 117:341–349

    Article  PubMed  CAS  Google Scholar 

  • Ledgerwood L, Richardson R, Cranney J (2004) d-cycloserine and the facilitation of extinction of conditioned fear: consequences for reinstatement. Behav Neurosci 118:505–513

    Article  PubMed  Google Scholar 

  • Ledgerwood L, Richardson R, Cranney J (2005) d-cycloserine facilitates extinction of learned fear: effects on reacquisition and generalized extinction. Biol Psychiatry 57:841–847

    Article  PubMed  CAS  Google Scholar 

  • Lingford-Hughes AR, Daglish MRC, Stevenson BJ et al (2006) Imaging alcohol cue exposure in alcohol dependence using a PET 15O-H20 paradigm: results from a pilot study. Addict Biol 11(1):107–15

    Article  PubMed  Google Scholar 

  • Min Z, Nix DE, Adam RD, CHjlds JM, Peloquin CA (2001) Pharmacokinetics of cycloserine under fasting conditions and with high-fat meal, orange juice, and antacids. Pharmacotherapy 21:891–897

    Article  Google Scholar 

  • Myers KM, Davis M (2002) Behavioral and neural analysis of extinction: a review. Neuron 36:567–584

    Article  PubMed  CAS  Google Scholar 

  • Norberg MM, Krystal JH, Tolin DF (2008) A meta-analysis of d-cycloserine and the facilitation of fear extinction and exposure therapy. Biol Psychiatry 63(12):1118–26

    Article  PubMed  CAS  Google Scholar 

  • Otto MW, Tolin DF, Simon NM et al (2010) Efficacy of d-cycloserine for enhancing response to cognitive-behavior therapy for panic disorder. Biol Psychiatry 67(4):365–70

    Article  PubMed  CAS  Google Scholar 

  • Raw M, Russell MA (1980) Rapid smoking, cue exposure and support in the modification of smoking. Behav Res Ther 18(5):363–72

    Article  PubMed  CAS  Google Scholar 

  • Ressler KJ, Rothbaum BO, Tannenbaum L et al (2004) Cognitive enhancers as adjuncts to psychotherapy: use of d-cycloserine in phobic individuals to facilitate extinction of fear. Arch Gen Psychiatry 61(11):1136–44

    Article  PubMed  Google Scholar 

  • Rothbaum BO (2008) Critical parameters for d-cycloserine enhancement of cognitive-behaviorial therapy for obsessive-compulsive disorder. Am J Psychiatry 165(3):293–6

    Article  PubMed  Google Scholar 

  • Santa Ana EJ, Rounsaville BJ, Frankforter TL et al (2009) d-Cycloserine attenuates reactivity to smoking cues in nicotine dependent smokers: a pilot investigation. Drug Alcohol Depend 104(3):220–7

    Article  PubMed  CAS  Google Scholar 

  • Spielberger C, Gorsuch R, Lushene R, Vagg P, Jacobs G. (1983) Manual for the State–Trait Anxiety Inventory. Consulting Psychologists’ Press.

  • Stockwell T, Murphy D, Hodgson R (1983) The severity of alcohol dependence questionnaire: its use, reliability and validity. Br J Addict 78:145–155

    Article  PubMed  CAS  Google Scholar 

  • Tiffany ST, Carter BL, Singleton EG (2000) Challenges in the manipulation, assessment and interpretation of craving relevant variables. Addiction 95(Suppl 2):S177–87

    PubMed  Google Scholar 

  • Walker DL, Ressler KJ, Lu KT, Davis M (2002) Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of d-cycloserine as assessed with fear-potentiated startle. J Neurosci 22:2343–2351

    PubMed  CAS  Google Scholar 

  • Weinstein A, Lingford-Hughes A, Martinez-Raga J, Marshall J (1998) What makes alcohol-dependent individuals early in abstinence crave for alcohol: exposure to the drink, images of drinking, or remembrance of drinks past? Alcohol Clin Exp Res 22(6):1376–81

    PubMed  CAS  Google Scholar 

  • Wilhelm S, Buhlmann U, Tolin DF et al (2008) Augmentation of behavior therapy with d-cycloserine for obsessive-compulsive disorder. Am J Psychiatry 165(3):335–41

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by the Avon and Wiltshire Mental Health Partnership NHS Trust R&D Department. There is no conflict of interest with any of the authors in relation to this article.

Funding

This study was funded by the Avon and Wiltshire Mental Health Partnership NHS Trust R&D Department.

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B. J. Watson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Watson, B.J., Wilson, S., Griffin, L. et al. A pilot study of the effectiveness of d-cycloserine during cue-exposure therapy in abstinent alcohol-dependent subjects. Psychopharmacology 216, 121–129 (2011). https://doi.org/10.1007/s00213-011-2199-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-011-2199-2

Keywords

Navigation