Advertisement

Psychopharmacology

, Volume 231, Issue 7, pp 1365–1375 | Cite as

Basal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and psychological distress in recreational ecstasy polydrug users

  • Mark A. WetherellEmail author
  • Catharine Montgomery
Original Investigation

Abstract

Rationale

Ecstasy (MDMA) is a psychostimulant drug which is increasingly associated with psychobiological dysfunction. While some recent studies suggest acute changes in neuroendocrine function, less is known about long-term changes in HPA functionality in recreational users.

Objectives

The current study is the first to explore the effects of ecstasy–polydrug use on psychological distress and basal functioning of the HPA axis through assessing the secretion of cortisol across the diurnal period.

Method

Seventy-six participants (21 nonusers, 29 light ecstasy–polydrug users, 26 heavy ecstasy–polydrug users) completed a substance use inventory and measures of psychological distress at baseline, then two consecutive days of cortisol sampling (on awakening, 30 min post awakening, between 1400 and 1600 hours and pre bedtime). On day 2, participants also attended the laboratory to complete a 20-min multitasking stressor.

Results

Both user groups exhibited significantly greater levels of anxiety and depression than nonusers. On day 1, all participants exhibited a typical cortisol profile, though light users had significantly elevated levels pre-bed. On day 2, heavy users demonstrated elevated levels upon awakening and all ecstasy–polydrug users demonstrated elevated pre-bed levels compared to non-users. Significant between group differences were also observed in afternoon cortisol levels and in overall cortisol secretion across the day.

Conclusions

The increases in anxiety and depression are in line with previous observations in recreational ecstasy–polydrug users. Dysregulated diurnal cortisol may be indicative of inappropriate anticipation of forthcoming demands and hypersecretion may lead to the increased psychological and physical morbidity associated with heavy recreational use of ecstasy.

Keywords

MDMA Ecstasy Cortisol HPA axis Cortisol awakening response 

Notes

Acknowledgements

The authors wish to thank Anthea Wilde for conducting the cortisol assays.

References

  1. Abercrombie HC, Giese-Davis J, Sephton S, Epel ES, Turner-Cobb JM, Spiegel D (2004) Flattened cortisol rhythms in metastatic breast cancer patients. Psychoneuroendocrinology 29:1082–1092PubMedCrossRefGoogle Scholar
  2. Arsenault-Lapierre G, Chertkow H, Lupien S (2010) Seasonal effects on cortisol secretion in normal aging, mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging 31:1051–1054PubMedCrossRefGoogle Scholar
  3. Bower JE, Ganz PA, Dickerson SS, Petersen L, Aziz N, Fahey JL (2005) Diurnal cortisol rhythm and fatigue in breast cancer survivors. Psychoneuroendocrinology 30:92–100PubMedCrossRefGoogle Scholar
  4. Boyle NT, Connor TJ (2010) Methylenedioxymethamphetamine (‘Ecstasy’)-induced immunosuppression: a cause for concern? Br J Pharmacol 161:17–32PubMedCentralPubMedCrossRefGoogle Scholar
  5. Buchanan TW, Kern S, Allen JS, Tranel D, Kirschbaum C (2004) Circadian regulation of cortisol after hippocampal damage in humans. Biol Psychiatry 56:651–656PubMedCrossRefGoogle Scholar
  6. Buske-Kirschbaum A, Geiben A, Hollig H, Morschhauser E, Hellhammer D (2002) Altered responsiveness of the hypothalamus–pituitary–adrenal axis and the sympathetic adrenomedullary system to stress in patients with atopic dermatitis. J Clin Endocrinol Metab 87:4245–4251PubMedCrossRefGoogle Scholar
  7. Carson DS, Bosanquet DP, Carter CS, Pournajafi-Nazarloo H, Blaszczynski A, McGregor IS (2012) Preliminary evidence for lowered basal cortisol in a naturalistic sample of methamphetamine polydrug users. Exp and Clin Psychopharmacol 20(6):497–503CrossRefGoogle Scholar
  8. Cole JC, Sumnall HR, Grob CS (2002) Sorted: Ecstasy facts and fiction. The Psychologist 15(9):464–467Google Scholar
  9. Connor TJ, Harkin A, Kelly JP (2005) Methylenedioxymethamphetamine suppresses production of the proinflammatory cytokine tumor necrosis factor-alpha independent of a beta-adrenoceptor-mediated increase in interleukin-10. J Pharmacol Exp Ther 312:134–143PubMedCrossRefGoogle Scholar
  10. Department of Health (2010) United Kingdom drug situation: annual report to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)Google Scholar
  11. Dumont GJ, Verkes RJ (2006) A review of acute effects of 3,4-methylenedioxymethamphetamine in healthy volunteers. J Psychopharmacol 20:176–187PubMedCrossRefGoogle Scholar
  12. Edwards S, Hucklebridge F, Clow A, Evans P (2003) Components of the diurnal cortisol cycle in relation to upper respiratory symptoms and perceived stress. Psychosom Med 65:320–327PubMedCrossRefGoogle Scholar
  13. Elder GJ, Wetherell MA, Barclay NL, Ellis JG (2013) The cortisol awakening response—Applications and implications for sleep medicine. Sleep Med Rev. doi:10.1016/j.smrv.2013.05.001Google Scholar
  14. Elenkov IJ (2004) Glucocorticoids and the Th1/Th2 balance. Ann N Y Acad Sci 1024:138–146PubMedCrossRefGoogle Scholar
  15. Fisk JE, Montgomery C (2009) Sleep impairment in ecstasy/polydrug and cannabis-only users. Am J Addict 18(5):430–437PubMedCrossRefGoogle Scholar
  16. Fisk JE, Montgomery C, Murphy P (2009) The association between the negative effects attributed to ecstasy use and measures of cognitive and mood among users. Hum Psychopharmacol Clin Exp 17(5):326–336CrossRefGoogle Scholar
  17. Fisk JE, Murphy PN, Montgomery C, Hadjefthyvoulou F (2010) Modelling the adverse effects associated with ecstasy use. Addiction 106:798–805PubMedCrossRefGoogle Scholar
  18. Fox HC, McLean A, Turner JJD, Parrott AC, Rogers R, Sahakian BJ (2002) Neuropsychological evidence of a relatively selective profile of temporal dysfunction in drug-free MDMA (“ecstasy”) polydrug users. Psychopharmacology 162:203–214PubMedCrossRefGoogle Scholar
  19. Fries E, Dettenborn L, Kirschbaum C (2009) The cortisol awakening response (CAR): facts and future directions. Int J Psychophys 72:67–73CrossRefGoogle Scholar
  20. Gerra G, Bassignana S, Zaimovic A, Moi G, Bussandri M, Caccavari R, Brambilla F, Molina E (2003) Hypothalamic–pituitary–adrenal axis responses to stress in subjects with 3,4-methylenedioxy-methamphetamine (‘ecstasy’)use history: correlation with dopamine receptor sensitivity. Psychiat Res 120:115–124CrossRefGoogle Scholar
  21. Gerra G, Zaimovic A, Chittolini B, Giucastro G, Folli F, Maestri D, Tessoni A, Avanzini P, Caccavari R, Bernasconi S, Brambilla F (1998) Neurotransmitter-hormonal responses to psychological stress in peripubertal subjects; relationship to aggressive behavior. Life Sci 62:617–625PubMedCrossRefGoogle Scholar
  22. Gold PW, Goodwin F, Chrousos GP (1998) Clinical and biochemical manifestations of depression: relationship to the neurobiology of stress. N Engl J Med 319:413–420CrossRefGoogle Scholar
  23. Harris DS, Baggott M, Mendelson JH, Mendelson JE, Jones RT (2002) Subjective and hormonal effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology 162:396–405PubMedCrossRefGoogle Scholar
  24. Hellhammer DH, Fries E, Scweisthal OW, Schlotz W, Stone AA, Hagemann D (2007) Several daily measurements are necessary to reliably assess the cortisol rise after awakening: state- and trait components. Psychoneuroendocrinlogy 32:80–86CrossRefGoogle Scholar
  25. Huber TJ, Issa K, Schik G, Wolf OT (2006) The cortisol awakening response is blunted in psychotherapy inpatients suffering from depression. Psychoneuroendocrinology 31:900–904PubMedCrossRefGoogle Scholar
  26. Johnson EO, Vlachoyiannopoulos PG, Skopouli FN, Tzioufas AG, Moutsopoulos HM (1998) Hypofunction of the stress axis in Sjogren’s syndrome. J Rheumatol 25:1508–1514PubMedGoogle Scholar
  27. Kiecolt-Glaser JK, McGuire L, Robles T, Glaser R (2002) Psychoneuroimmunology and psychosomatic medicine: back to the future. Psychosom Med 64:15–28PubMedGoogle Scholar
  28. Kraemer HC, Giese‐Davis J, Yutsis MBA, O’Hara R, Neri EBS, Gallagher‐Thompson D, Taylor CB, Spiegel D (2006) Design decisions in order to optimise reliability of daytime diurnal slopes in an older population. Am J Geriatr Psychiatry 14:325–333Google Scholar
  29. Kudielka BM, Broderick JE, Kirschbaum C (2003) Compliance with saliva sampling protocols: electronic monitoring reveals invalid cortisol profiles in noncompliant subjects. Psychosom Med 65:313–319PubMedCrossRefGoogle Scholar
  30. Kudielka BM, Kirschbaum C (2003) Awakening cortisol responses are influenced by health status and awakening time but not by menstrual cycle phase. Psychoneuroendocrinology 28:35–47PubMedCrossRefGoogle Scholar
  31. Lovell B, Moss M, Wetherell MA (2011) The psychosocial, endocrine and immune consequences of caring for a child with autism or ADHD. Psychoneuroendocrinology 37:534–542PubMedCrossRefGoogle Scholar
  32. Lovell B, Moss MC, Wetherell MA (2012) With a little help from my friends: Psychological, endocrine and health corollaries of social support in parental caregivers of children with autism and ADHD. Res Dev Disabilit 33(2):682–687CrossRefGoogle Scholar
  33. Lupien S, de Leon M, de Santi S, Convit A, Tarshish C, Nair N, Thakur M, McEwen B, Hauger R, Meaney M (1998) Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci 1:69–73PubMedCrossRefGoogle Scholar
  34. Mas M, Farre M, de la Torre R, Roset PN, Ortuno J, Segura J, Cami J (1999) Cardiovascular and neuroendocrine effects and pharmacokinetics of 3,4-methylenedioxymethamphetaminein humans. J Pharmacol Exp Ther 290:136–145PubMedGoogle Scholar
  35. Masi AT, Chrousos GP (1996) Hypothalamic–pituitary–adrenal–glucocorticoid axis function in rheumatoid arthritis. J Rheumatol 23:577–581PubMedGoogle Scholar
  36. McCann UD, Sgambati FP, Schwartz AR, Ricaurte GA (2009) Sleep apnea in young abstinent recreational MDMA (“ecstasy”) consumers. Neurology 8(73):2011–7CrossRefGoogle Scholar
  37. McCardle K, Luebbers JD, Carter JD, Croft RJ, Stough C (2004) Chronic MDMA (ecstasy) use, cognition and mood. Psychopharmacology 173:434–439PubMedCrossRefGoogle Scholar
  38. McEwen BS (1998) Protective and damaging effects of stress mediators. N Engl J Med 338(3):171–9PubMedCrossRefGoogle Scholar
  39. Miller GE, Chen E, Zhou ES (2007) If it goes up, must it come down? Chronic stress and the hypothalamic–pituitary adrenocortical axis in humans. Psychol Bull 133(1):25–45PubMedCrossRefGoogle Scholar
  40. Montgomery C, Fisk JE, Newcombe R, Murphy PN (2005) The differential effects of ecstasy/polydrug use on executive components: shifting, inhibition, updating and access to semantic memory. Psychopharmacology 182:262–276PubMedCrossRefGoogle Scholar
  41. Montgomery C, Fisk JE, Wareing M, Murphy P (2007) Self reported sleep quality and cognitive performance in ecstasy users. Hum Psychopharmacol 22(8):537–548PubMedCrossRefGoogle Scholar
  42. Montgomery C, Hatton NP, Fisk JE, Ogden RS, Jansari A (2010) Assessing the functional significance of ecstasy-related memory deficits using a virtual paradigm. Hum Psychopharmacol 25(4):318–325PubMedCrossRefGoogle Scholar
  43. Murphy PN, Wareing M, Fisk JE, Montgomery C (2009) Executive working memory deficits in abstinent ecstasy/MDMA users: a critical review. Neuropsychobiology 60:159–175PubMedCrossRefGoogle Scholar
  44. NIH National Institute on Drug Abuse (2012) Monitoring the futureGoogle Scholar
  45. Okun ML, Krafty RT, Buysse DJ, Monk TJ, Reynolds CF, Begley A, Hall M (2010) What constitutes too long of a delay? Determining the cortisol awakening response (CAR) using self report and PSG-assessed wake time. Psychoneuroendocrinology 35:460–468PubMedCentralPubMedCrossRefGoogle Scholar
  46. Oskis A, Loveday C, Hucklebridge F, Thorn L, Clow A (2009) Diurnal patterns of salivary cortisol across the adolescent period in healthy females. Psychoneuroendocrinology 34:307–316PubMedCrossRefGoogle Scholar
  47. Pacifici R, Zuccaro P, Farre M, Pichini S, Di Carlo S, Roset PN, Ortuno J, Pujadas M, Bacosi A, Menoyo E, Segura J, de la Torre R (2001) Effects of repeated doses of MDMA (‘ecstasy’) on cell-mediated immune response in humans. Life Sci 69:2931–2941PubMedCrossRefGoogle Scholar
  48. Pacifici R, Zuccaro P, Farré M, Poudevida S, Abanades S, Pichini S, Langohr K, Segura J, de la Torre R (2007) Combined immunomodulating properties of 3,4-methylenedioxymethamphetamine (MDMA) and cannabis in humans. Addiction 102(6):931–6PubMedCrossRefGoogle Scholar
  49. Parrot AC (2004) Is ecstasy MDMA? A review of the proportion of ecstasy tablets containing MDMA, their dosage levels, and the changing perceptions of purity. Psychopharmacology 173(3–4):234–41CrossRefGoogle Scholar
  50. Parrott AC (2006) MDMA in humans: factors which affect neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress. J Psychopharmacol 20(2):147–163PubMedCrossRefGoogle Scholar
  51. Parrott AC (2009) Cortisol and 3,4‐Methylenedioxymethamphetamine: Neurohormonal aspects of bioenergetic stress in ecstasy users. Neuropsychobiology 60:148–158Google Scholar
  52. Parrott AC, Buchanan T, Scholey AB, Heffernan TM, Ling J, Rodgers J (2002) Ecstasy-attributed problems reported by novice, moderate and heavy recreational users. Hum Psychopharmacol 17:309–312PubMedCrossRefGoogle Scholar
  53. Parrott AC, Gibbs A, Scholey AB, King R, Owens K, Swann P, Ogden E, Stough C (2011) MDMA and methamphetamine: some paradoxical negative and positive mood changes in an acute dose laboratory study. Psychopharmacology 215:527–536PubMedCrossRefGoogle Scholar
  54. Parrott AC, Lock J, Conner A, Kissling C, Thome J (2008) Dance clubbing on MDMA and during abstinence from ecstasy/MDMA: prospective neuroendocrine and psychobiological changes. Neuropsychobiology 57:165–180PubMedCentralPubMedCrossRefGoogle Scholar
  55. Parrott AC, Milani RM, Gouzoulis-Mayfrank E, Daumann J (2007) Cannabis and ecstasy/MDMA (3,4-methylenedioxymethamphetamine): an analysis of their neuropsychobiological interactions in recreational users. J Neural Trans 114:959–968CrossRefGoogle Scholar
  56. Pruessner JC, Kirschbaum C, Meinlschmid G, Hellhammer DH (2003) Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 28:916–931PubMedCrossRefGoogle Scholar
  57. Pruessner M, Vracotas N, Joober R, Pruessner JC, Malla AK (2013) Blunted cortisol awakening response in men with first episode psychosis: relationship to parental bonding. Psychoneuroendocrinology 38:229–240PubMedCrossRefGoogle Scholar
  58. Reay JL, Hamilton C, Kennedy DO, Scholey AB (2006) MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes. J Psychopharmacol 20:385–388PubMedCrossRefGoogle Scholar
  59. Roberts C, Fairclough S, Fisk J, Tames F, Montgomery C (2013a) Electrophysiological indices of response inhibition in human polydrug users. J Psychopharmacol 27(9):779–789PubMedCrossRefGoogle Scholar
  60. Roberts CA, Fairclough SF, Fisk JE, Tames F, Montgomery CA (2013b) ERP evidence suggests executive dysfunction in ecstasy polydrug users. Psychopharmacology 3(228):375–388CrossRefGoogle Scholar
  61. Rodgers J, Buchanan T, Pearson C, Parrott AC, Heffernan T, Scholey AB (2006) Differential experiences of the psychobiological sequelae of ecstasy use: quantitative and qualitative data from an internet study. J Psychopharmacol 20(3):437–446PubMedCrossRefGoogle Scholar
  62. Rosmond R (2005) Role of stress in the pathogenesis of the metabolic syndrome. Psychoneuroendocrinology 30:1–10PubMedCrossRefGoogle Scholar
  63. Saxbe DE (2008) A field (researcher’s) guide to cortisol: tracking HPA axis functioning in everyday life. Health Psych Rev 2(2):163–190CrossRefGoogle Scholar
  64. Scholey AB, Owen L, Gates J, Rodgers J, Buchanan T, Ling J, Heffernan T, Swan P, Stough C, Parrott AC (2011) Hair MDMA samples are consistent with reported ecstasy use: findings from a study investigating effects of ecstasy on mood and memory. Neuropsychobiology 63:15–21PubMedCrossRefGoogle Scholar
  65. Scholtz W, Hellhammer J, Schulz P, Stone AA (2004) Perceived workoverload and chronic worrying predict weekend–weekday differences in the cortisol awakening response. Psychosom Med 6:207–214CrossRefGoogle Scholar
  66. Schulz P, Kirschbaum C, Pruessner JC, Hellhamer D (1998) Increased free cortisol secretion after awakening in chronically stressed individuals due to workload. Stress Med 14:91–97CrossRefGoogle Scholar
  67. Sephton SE, Sapolsky RM, Kraemer HC, Spiegel D (2000) Diurnal cortisol rhythm as a predictor of breast cancer survival. J Natl Cancer Ins 92(12):994–1000CrossRefGoogle Scholar
  68. Snaith RP (2003) The Hospital Anxiety and Depression Scale: commentary. Health Qual Life Outcomes 1:29PubMedCentralPubMedCrossRefGoogle Scholar
  69. Solowij N, Battisti R (2008) The chronic effects of cannabis on memory in humans: a review. Curr Drug Abuse Rev 1:81–98PubMedCrossRefGoogle Scholar
  70. Solowij N, Hall W, Lee N (1992) Recreational MDMA use in Sydney: a profile of ecstasy users and their experiences with the drug. Br J Addict 87:1161–1172PubMedCrossRefGoogle Scholar
  71. Stalder T, Hucklebridge F, Evans P, Clow A (2009) Use of a single case study design to examine state variation in the cortisol awakening response: Relationship with time of awakening. Psychoneuroendocrinology 34:607–614PubMedCrossRefGoogle Scholar
  72. Verheul R (2001) Co-morbidity of personality disorders in individuals with substance use disorders. Eur Psychiatry 16:274–282PubMedCrossRefGoogle Scholar
  73. Verheyden SL, Henry JA, Curran V (2003) Acute, sub-acute and long-term subjective consequences of ‘ecstasy’ (MDMA) consumption in 430 regular users. Hum Psychopharmacol 18:507–517PubMedCrossRefGoogle Scholar
  74. Wetherell MA, Atherton K, Grainger J, Brosman R, Scholey AB (2012) The effects of multi-tasking on psychological stress reactivity in recreational drug users. Hum Psychopharmacol Clin Exp 27(2):167–176CrossRefGoogle Scholar
  75. Wolff K, Aitchison KJ (2013) Reply to ‘MDMA can increase cortical levels by 800% in dance clubbers’ Parrott, et al. J Psychopharmacol 27:115Google Scholar
  76. Wolff K, Tsapakis EM, Pariante CM, Kerwin RW, Forsling ML, Aitchison KJ (2012) Pharmacogenetic studies of changes in cortisol on ecstasy (MDMA) consumption. J Psychopharmacol 26(3):419–428Google Scholar
  77. Wolf OT, Fujiwara E, Luwinski G, Kirschbaum C, Markowitsch HJ (2005) No morning cortisol response in patients with severe global amnesia. Psychoneuroendocrinology 30:101–105PubMedCrossRefGoogle Scholar
  78. Zakzanis KK, Campbell Z, Jovanovski D (2007) The neuropsychology of ecstasy (MDMA) use: a quantitative review. Hum Psychopharmacol 22:427–435PubMedCrossRefGoogle Scholar
  79. Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67(6):361–70PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Health in Action Stress Research Group, Department of PsychologyUniversity of NorthumbriaNewcastle-upon-TyneUK
  2. 2.School of Natural Sciences and PsychologyLiverpool John Moores UniversityLiverpoolUK

Personalised recommendations