Skip to main content
SpringerLink
Log in

Resting EEG and ERPs findings in methadone-substituted opiate users: a review

  • Review Article
  • Published:
Acta Neurologica Belgica Aims and scope Submit manuscript

Abstract

Methadone has been used to treat opiate dependence since the mid-1960s. Despite its clinical effectiveness there is evidence from neuropsychological studies demonstrating that its long-term use might have negative effects on cognition. Nevertheless, it remains uncertain whether the observed cognitive impairments in patients undertaking methadone maintenance treatment (MMT) are solely attributable to the pharmacological effects of methadone, as suggested by some researchers. Determining the effects of MMT on neuropsychological function using electroencephalography (EEG) combined with event-related potentials (ERP) has been used infrequently. However EEG and ERP provide a means of closely examining information processing to determine whether MMT induces any deficits. The purpose of this review was to investigate whether psychophysiological evidence supports cognitive impairment in association with MMT by focusing on research using EEG and ERPs. The findings of EEG studies to date appear not support the notion that cognitive impairments are attributable to the specific pharmacological effects of methadone suggested by some neuropsychological studies. However, due to the methodological deficits and limited number of the studies, any conclusion based on the findings of the existing EEG studies should be avoided.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Garrido MJ, Trocóniz IF (1999) Methadone: a review of its pharmacokinetic/pharmacodynamic properties. J Pharmacol Toxicol Methods 42(2):61–66

    Article  CAS  PubMed  Google Scholar 

  2. Marsch LA (1998) The efficacy of methadone maintenance interventions in reducing illicit opiate use, HIV risk behavior and criminality: a meta-analysis. Addiction 93(4):515–532

    Article  CAS  PubMed  Google Scholar 

  3. Gibson DR, Flynn NM, McCarthy JJ (1999) Effectiveness of methadone treatment in reducing HIV risk behavior and HIV seroconversion among injecting drug users. Aids 13(14):1807–1818

    Article  CAS  PubMed  Google Scholar 

  4. Wang GY, Wouldes TA, Russell BB (2013) Methadone maintenance treatment and cognitive function: a systematic review. Curr Drug Abuse Rev 6(3):220–230

    Article  CAS  PubMed  Google Scholar 

  5. Prosser J, Cohen LJ, Steinfeld M, Eisenberg D, London ED, Galynker II (2006) Neuropsychological functioning in opiate-dependent subjects receiving and following methadone maintenance treatment. Drug Alcohol Depen 84(3):240–247 PubMed PMID: 2006420273

    Article  Google Scholar 

  6. Verdejo A, Toribio I, Orozco C, Puente KL, Perez-Garcia M (2005) Neuropsychological functioning in methadone maintenance patients versus abstinent heroin abusers. Drug Alcohol Depen 78(3):283–288 PubMed PMID: 2005225732

    Article  CAS  Google Scholar 

  7. Darke S, Sims J, McDonald S, Wickes W (2000) Cognitive impairment among methadone maintenance patients. Addiction 95(5):687–695

    Article  CAS  PubMed  Google Scholar 

  8. Mintzer MZ, Stitzer ML (2002) Cognitive impairment in methadone maintenance patients. Drug Alcohol Depen 67(1):41–51

    Article  Google Scholar 

  9. Rapeli P, Fabritius C, Kalska H, Alho H (2009) Memory function in opioid-dependent patients treated with methadone or buprenorphine along with benzodiazepine: longitudinal change in comparison to healthy individuals. Subst Abuse Treat Pr 4(6):1–15

    Google Scholar 

  10. Pirastu R, Fais R, Messina M, Bini V, Spiga S, Falconieri D et al (2006) Impaired decision-making in opiate-dependent subjects: effect of pharmacological therapies. Drug Alcohol Depen 83(2):163–168 (PubMed PMID: Peer Reviewed Journal: 2006-07783-009)

    Article  CAS  Google Scholar 

  11. Rapeli P, Fabritius C, Alho H, Salaspuro M, Wahlbeck K, Kalska H (2007) Methadone vs. buprenorphine/naloxone during early opioid substitution treatment: a naturalistic comparison of cognitive performance relative to healthy controls. BMC Clin Pharmacol 7(1):5

    Article  PubMed Central  PubMed  Google Scholar 

  12. Davis PE, Liddiard H, McMillan TM (2002) Neuropsychological deficits and opiate abuse. Drug Alcohol Depen 67(1):105–108 (PubMed PMID: Peer Reviewed Journal: 2002-17450-011)

    Article  CAS  Google Scholar 

  13. Soyka M, Lieb M, Kagerer S, Zingg C, Koller G, Lehnert P et al (2008) Cognitive functioning during methadone and buprenorphine treatment: results of a randomized clinical trial. J Clin Psychopharmacol 28(6):699–703

    Article  CAS  PubMed  Google Scholar 

  14. Appel PW (1982) Sustained attention in methadone patients. Subst Use Misuse 17:1313–1327

    Article  CAS  Google Scholar 

  15. Appel P, Gordon N (1976) Digit-symbol performance in methadone-treated ex-heroin addicts. Am J Psychiatry 133:1337–1340

    Article  CAS  PubMed  Google Scholar 

  16. Specka M, Finkbeiner T, Lodemann E, Leifert K, Kluwig J, Gastpar M (2000) Cognitive-motor performance of methadone-maintained patients. Eur Addict Res 6:8–19

    Article  CAS  PubMed  Google Scholar 

  17. Grevert P, Masover B, Goldstein A (1977) Failure of methadone and levomethadyl acetate (levo-alpha-acetylmethadol, LAAM) maintenance to affect memory. Arch Gen Psychiatry 34(7):849–853 (PubMed PMID: Peer Reviewed Journal: 1978-12936-001)

    Article  CAS  PubMed  Google Scholar 

  18. Ersche KD, Roiser JP, Clark L, London M, Robbins TW, Sahakian BJ (2005) Punishment induces risky decision-making in methadone-maintained opiate users but not in heroin users or healthy volunteers. Neuropsychopharmacology 30(11):2115–2124

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Gordon NB (1970) Reaction-times of methadone treated ex heroin addicts. Psychopharmacology. 16:337–344

    Google Scholar 

  20. Rothenberg S, Meyer RE, Rauss B, Gross K (1977) Performance differences between addicts and non-addicts. Psychopharmacology 52(3):299–306

    Article  CAS  PubMed  Google Scholar 

  21. Corradini PL, Persinger MA (2014) Spectral power, source localization and microstates to quantify chronic deficits from ‘mild’ closed head injury: correlation with classic neuropsychological tests. Brain Inj 2014(28):1317–1327

    Article  Google Scholar 

  22. Klimesch W, Vogt F, Doppelmayr M (1999) Interindividual differences in alpha and theta power reflect memory performance. Intelligence 27(4):347–362

    Article  Google Scholar 

  23. Ray W, Cole H (1985) EEG alpha activity reflects attentional demands, and beta activity reflects emotional and cognitive processes. Science 228(4700):750–752

    Article  CAS  PubMed  Google Scholar 

  24. Barry RJ, Clarke AR, Johnstone SJ, Magee CA, Rushby JA (2007) EEG differences between eyes-closed and eyes-open resting conditions. Clin Neurophysiol 118(12):2765–2773

    Article  PubMed  Google Scholar 

  25. Alexander DM, Trengove C, Wright JJ, Boord PR, Gordon E (2006) Measurement of phase gradients in the EEG. J Neurosci Methods 156(1–2):111–128

    Article  CAS  PubMed  Google Scholar 

  26. Klimesch W, Sauseng P, Hanslmayr S (2007) EEG alpha oscillations: the inhibition–timing hypothesis. Brain Res Rev 53:63–88

    Article  PubMed  Google Scholar 

  27. Gritz ER, Shiffman SM, Jarvik ME, Haber J, Dymond AM, Coger R et al (1975) Physiological and psychological effects of methadone in man. Arch Gen Psychiatry 32(2):237–242

    Article  CAS  PubMed  Google Scholar 

  28. Feinstein B, Hanley J (1975) EEG findings in heroin addicts during induction and maintenance on methadone. Electroencephalogr Clin Neurophysiol 39(1):96–99

    Article  CAS  PubMed  Google Scholar 

  29. Fingelkurts AA, Fingelkurts AA, Kivisaari R, Autti T, Borisov S, Puuskari V et al (2007) Composition of EEG oscillations and their temporal characteristics. Int J Psychophysiol 64:130–140

    Article  Google Scholar 

  30. Fingelkurts AA, Fingelkurts AA, Kivisaari R, Autti T, Borisov S, Puuskari V et al (2009) Methadone restores local and remote EEG functional connectivity in opioid. Int J Neurosci 119(9):1469–1493

    Article  PubMed  Google Scholar 

  31. Gorricho D, Valdizanuson JR (2008) QEEG mapping and methadone. Eur J Psychiat Online 22(1):29–37

    Google Scholar 

  32. Kay DC (1975) Human sleep and EEG through a cycle of methadone dependence. Electroencephalogr Clin Neurophysiol 38(1):35–43

    Article  CAS  PubMed  Google Scholar 

  33. Lenn NJ, Senay EC, Renault PF, Deuel RK (1976) Neurological assessment of patients on prolonged methadone maintenance. Drug Alcohol Depen 1(4):305–311

    Article  CAS  Google Scholar 

  34. Martin WR, Jasinski DR, Haertzen CA, Kay DC, Jones BE, Mansky PA et al (1973) Methadone–a reevaluation. Arch Clin Neuropsychol 28(2):286–295

    CAS  Google Scholar 

  35. Wang GY, Kydd R, Wouldes TA, Jensen M, Russell BR (2015) Changes in resting EEG following methadone treatment in opiate addicts. Clin Neurophysiol 126:943–950

    Article  PubMed  Google Scholar 

  36. Danion JM, Weingartner H, File SE, Jaffard R, Sunderland T, Tulving E et al (1993) Pharmacology of human memory and cognition: illustrations from the effects of benzodiazepines and cholinergic drugs. J Psychopharmacol 7(4):371–377

    Article  CAS  PubMed  Google Scholar 

  37. Oades R, Dittmann-Balcar A, Schepker R, Eggers C, Zerbin D (1996) Auditory event-related potentials (ERPs) and mismatch negativity (MMN) in healthy children and those with attentiondeficitor Tourettic symptoms. Biol Psychol 43:163–185

    Article  CAS  PubMed  Google Scholar 

  38. Laurent A, Garcia-Larréa L, d’Amato T, Bosson J, Saoud M, Marie-Cardine M (1999) Auditory event-related potentials and clinical scores in unmedicated schizophrenic patients. Psychiatry Res 86:229–238

    Article  CAS  PubMed  Google Scholar 

  39. Llinás R, Ribary U (1993) Coherent 40-Hz oscillation characterizes dream state in humans. Proceed Natl Acad Sci 90(5):2078–2081

    Article  Google Scholar 

  40. Boutros NN, Torello M, McGlashan TH (2003) Electrophysiological Aberrations in Borderline Personality Disorder: State of the Evidence The Journal of Neuropsychiatry and Clinical Neurosciences. 15:145–154

    PubMed  Google Scholar 

  41. Markand ON (2003) Pearls, perils, and pitfalls in the use of the electroencephalogram. Semin Neurol 23(1):7–46

    Article  PubMed  Google Scholar 

  42. Wolff K, Rostami-Hodjegan A, Hay AWM, Raistrick D, Tucker G (2000) Population-based pharmacokinetic approach for methadone monitoring of opiate addicts: potential clinical utility. Addiction 95(12):1771–1783

    Article  CAS  PubMed  Google Scholar 

  43. Ceballos NA, Bauer L, Houston R (2009) Recent EEG and ERP findings in substance abusers. Clin EEG Neurosci 40(2):122–128

    Article  PubMed Central  PubMed  Google Scholar 

  44. Halgren E, Marinkovic K, Chauvel P (1998) Generators of the late cognitive potentials in auditory and visual oddball tasks. Electroencephalogr Clin Neurophysiol 106(2):156–164

    Article  CAS  PubMed  Google Scholar 

  45. Mulert C, Pogarell O, Hegerl U (2010) Event-related potentials in psychiatry and clinical pharmacology:Basics, applicationa and relationship to fMRI. In: Drinkenburg WHIM, Ruigt GSF, Jobert M (eds) Essentials and applications of EEG research in preclinical and clinical pharmacology. IPEG, Belgium, pp 165–172

    Google Scholar 

  46. Tecce JJ, Cole JO, Mayer J, Lewis DC (1979) Methadone effects on brain functioning and Type A and B CNV shapes. Psychopharmacology 65(1):21–25

    Article  CAS  PubMed  Google Scholar 

  47. Nagai Y, Critchley HD, Featherstone E, Fenwick PBC, Trimble MR, Dolan RJ (2004) Brain activity relating to the contingent negative variation: an fMRI investigation. NeuroImage 21(4):1232–1241

    Article  CAS  PubMed  Google Scholar 

  48. Pritchard W, Sokhadze E, Houlihan M (2004) Effects if nicotine and smoking on event-related potentials: a reivew. Nicotine Tob Res. 6(6):961–984

    Article  CAS  PubMed  Google Scholar 

  49. Di Russo F, Pitzalis S, Spitoni G, Aprile T, Patria F, Spinelli D et al (2005) Identification of the neural sources of the pattern-reversal VEP. NeuroImage 24(3):874–886

    Article  PubMed  Google Scholar 

  50. Bauer L (1998) Effects of chronic opioid dependence and HIV-1 infection on pattern shift visual evoked potentials. Drug Alcohol Depen 50(2):147–155

    Article  CAS  Google Scholar 

  51. Patel S, Azzam P (2005) Characterization of N200 and P300: selected studies of the event-related potential. Int J Med Sci 2(4):147–154

    Article  PubMed Central  PubMed  Google Scholar 

  52. Wickens C, Karmer A, Vanasse L, Donchin E (1983) The performance of concurrent tasks:a psychophysiological analysis of the reciprocity of inofrmation processsing resources. Science 221:1080–1082

    Article  CAS  PubMed  Google Scholar 

  53. Polich J (1986) Attention, probability, and task demands as determinants of P300 latency from auditory stimuli. Electroencephalogr Clin Neurophysiol 63(3):251–259

    Article  CAS  PubMed  Google Scholar 

  54. Alexander JE, Bauer LO, Kuperman S, Morzorati S, O’Connor SJ, Rohrbaugh J et al (1996) Hemispheric differences for P300 amplitude from an auditory oddball task. Int J Psychophysiol 21(2–3):189–196

    Article  CAS  PubMed  Google Scholar 

  55. Attou A, Figiel C, Timsit-Berthier M (2001) Opioid addiction: P300 assessment in treatment by methadone substitution. Neurophysiol Clin 31(3):171–180

    Article  CAS  PubMed  Google Scholar 

  56. Kouri E, Lukas S, Mendelson J (1996) P300 assessment of opiate and cocaine users: effects of detoxification and buprenorphine treatment. Biol Psychoiatry 40:617–628

    Article  CAS  Google Scholar 

  57. Muller BW, Specka M, Steinchen N, Zerbin D, Lodemann E, Finkbeiner T et al (2007) Auditory target processing in methadone substituted opiate addicts: The effect of nicotine in controls. BMC Psychiatry 7:1–9 (PubMed PMID: Peer Reviewed Journal: 2008-10167-001)

    Article  Google Scholar 

  58. Yang L, Xu Q, Li S, Zhao X, Ma L, Zheng Y, et al. (2015) The effects of methadone maintenance treatment on heroin addicts with response inhibition function impairments: evidence from event-related potentials. J Food Drug Anal (in Press)

  59. Hart CL, Marvin CB, Silver R, Smith EE (2012) Is cognitive functioning impaired in methamphetamine users [quest] a critical review. Neuropsychopharmacology 37(3):586–608

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Hart CL, Ilan AB, Gevins A, Gunderson EW, Role K, Colley J et al (2010) Neurophysiological and cognitive effects of smoked marijuana in frequent users. Pharmacol Biochem Behav 96(3):333–341

    Article  CAS  PubMed  Google Scholar 

  61. Gevins A, Ilan AB, Jiang A, Sam-Vargas L, Baum C, Chan CS (2011) Combined neuropsychological and neurophysiological assessment of drug effects on groups and individuals. J Psychopharmcol 25:1062–1075

    Article  CAS  Google Scholar 

  62. Kenemans JL, Kahkonen S (2011) How Human Electrophysiology Informs Psychopharmacology: from Bottom-up Driven Processing to Top-Down Control. Neuropsychopharmacology 36(1):26–51

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare no conflict of interest.

Ethical standard

This article does not include any studies with animals performed by any of the authors.

Author information

Authors and Affiliations

  1. Department of Psychology, Auckland University of Technology, Auckland, New Zealand

    Grace Y. Wang

  2. Centre for Brain Research, University of Auckland, Auckland, New Zealand

    Robert Kydd & Bruce R. Russell

  3. Department of Psychological Medicine, University of Auckland, Auckland, New Zealand

    Robert Kydd

  4. School of Pharmacy, University of Auckland, Auckland, New Zealand

    Bruce R. Russell

Authors
  1. Grace Y. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert Kydd
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bruce R. Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Grace Y. Wang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, G.Y., Kydd, R. & Russell, B.R. Resting EEG and ERPs findings in methadone-substituted opiate users: a review. Acta Neurol Belg 115, 539–546 (2015). https://doi.org/10.1007/s13760-015-0476-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13760-015-0476-2

Keywords

Search

Navigation