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MDMA does not alter responses to the Trier Social Stress Test in humans

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Abstract

Rationale

±3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a stimulant-psychedelic drug with unique social effects. It may dampen reactivity to negative social stimuli such as social threat and rejection. Perhaps because of these effects, MDMA has shown promise as a treatment for post-traumatic stress disorder (PTSD). However, the effect of single doses of MDMA on responses to an acute psychosocial stressor has not been tested.

Objectives

In this study, we sought to test the effects of MDMA on responses to stress in healthy adults using a public speaking task. We hypothesized that the drug would reduce responses to the stressful task.

Methods

Volunteers (N = 39) were randomly assigned to receive placebo (N = 13), 0.5 mg/kg MDMA (N = 13), or 1.0 mg/kg MDMA (N = 13) during a stress and a no-stress session. Dependent measures included subjective reports of drug effects and emotional responses to the task, as well as salivary cortisol, heart rate, and blood pressure.

Results

The stress task produced its expected increase in physiological responses (cortisol, heart rate) and subjective ratings of stress in all three groups, and MDMA produced its expected subjective and physiological effects. MDMA alone increased ratings of subjective stress, heart rate, and saliva cortisol concentrations, but contrary to our hypothesis, it did not moderate responses to the Trier Social Stress Test.

Conclusions

Despite its efficacy in PTSD and anxiety, MDMA did not reduce either the subjective or objective responses to stress in this controlled study. The conditions under which MDMA relieves responses to negative events or memories remain to be determined.

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References

  • Adam EK, Kumari M (2009) Assessing salivary cortisol in large-scale, epidemiological research. Psychoneuroendocrinology 34:1423–1436

    Article  CAS  PubMed  Google Scholar 

  • Baggott MJ, Coyle JR, Siegrist JD, Garrison KJ, Galloway GP, Mendelson JE (2015) Effects of MDMA on socioemotional feelings, authenticity, and autobiographical disclosure in healthy volunteers in a controlled setting. doi:10.1101/021329

  • Bedi G, Phan KL, Angstadt M, de Wit H (2009) Effects of MDMA on sociability and neural response to social threat and social reward. Psychopharmacology 207:73–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bedi G, Hyman D, de Wit H (2010) Is ecstasy an "empathogen": effects of ±3, 4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others. Biol Psychiatry 68:1134–1140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bershad AK, Miller MA, Baggott MJ, de Wit H (2016) The effects of MDMA on socio-emotional processing: does MDMA differ from other stimulants? J Psychopharmacol. doi:10.1177/0269881116663120

    Google Scholar 

  • Bouso JC, Doblin R, Farre M, Alcazar MA, Gomez-Jarabo G (2008) MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. J Psychoactive Drugs 40:225–236

    Article  PubMed  Google Scholar 

  • Curran HV (2000) Is MDMA (‘ecstasy’) neurotoxic in humans? An overview of evidence and of methodological problems in research. Neuropsychobiology 42:34–41

    Article  CAS  PubMed  Google Scholar 

  • Dumont G, Sweep F, Van der Steen R, Hermsen R, Donders A, Touw D, van Gerven J, Buitelaar J, Verkes R (2009) Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3, 4-methylenedioxymethamphetamine) administration. Soc Neurosci 4:359–366

    Article  CAS  PubMed  Google Scholar 

  • Fischman MW, Foltin RW (1991) Utility of subjective effects measurements in assessing abuse liability of drugs in humans. Br J Addict 86:1563–1570

    Article  CAS  PubMed  Google Scholar 

  • Frye CG, Wardle MC, Norman GJ, de Wit H (2014) MDMA decreases the effects of simulated social rejection. Pharmacol Biochem Behav 117:1–6

    Article  CAS  PubMed  Google Scholar 

  • Gaab J, Rohleder N, Nater U, Ehlert U (2005) Psychological determinants of the cortisol stress response: the role of anticipatory cognitive appraisal. Psychoneuroendocrinology 30:599–610

    Article  CAS  PubMed  Google Scholar 

  • 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. Psychiatry Res 120:115–124

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U (2003) Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry 54:1389–1398

    Article  CAS  PubMed  Google Scholar 

  • Hysek C, Simmler L, Ineichen M, Grouzmann E, Hoener M, Brenneisen R, Huwyler J, Liechti M (2011) The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA (“ecstasy”) in humans. Clinical pharmacology & therapeutics 90:246–255

    Article  CAS  Google Scholar 

  • Hysek CM, Domes G, Liechti ME (2012) MDMA enhances “mind reading” of positive emotions and impairs “mind reading” of negative emotions. Psychopharmacology 222:293–302

    Article  CAS  PubMed  Google Scholar 

  • Hysek CM, Schmid Y, Simmler LD, Domes G, Heinrichs M, Eisenegger C, Preller KH, Quednow BB, Liechti ME (2013) MDMA enhances emotional empathy and prosocial behavior. Soc Cogn Affect Neurosci 9:1645

  • Kamilar-Britt P, Bedi G (2015) The prosocial effects of 3, 4-methylenedioxymethamphetamine (MDMA): controlled studies in humans and laboratory animals. Neurosci Biobehav Rev 57:433–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirkpatrick MG, Gunderson EW, Perez AY, Haney M, Foltin RW, Hart CL (2012) A direct comparison of the behavioral and physiological effects of methamphetamine and 3, 4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology 219:109–122

    Article  CAS  PubMed  Google Scholar 

  • Kirkpatrick MG, Francis SM, Lee R, de Wit H, Jacob S (2014a) Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans. Psychoneuroendocrinology 46:23–31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirkpatrick MG, Lee R, Wardle MC, Jacob S, de Wit H (2014b) Effects of MDMA and intranasal oxytocin on social and emotional processing. Neuropsychopharmacology 39:1654–1663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirkpatrick M, Delton AW, de Wit H, Robertson TE (2015) Prosocial effects of MDMA: a measure of generosity. J Psychopharmacol. doi:10.1177/0269881115573806

    PubMed Central  Google Scholar 

  • Kirschbaum C, Pirke K-M, Hellhammer DH (1993) The ‘Trier social stress test’—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28:76–81

    Article  CAS  PubMed  Google Scholar 

  • Kirschbaum C, Kudielka BM, Gaab J, Schommer NC, Hellhammer DH (1999) Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosom Med 61:154–162

    Article  CAS  PubMed  Google Scholar 

  • Kudielka BM, Hellhammer DH, Kirschbaum C, Harmon-Jones E, Winkielman P (2007) Ten years of research with the Trier social stress test—revisited. Social neuroscience: Integrating biological and psychological explanations of social behavior:56–83

  • Kuypers KP, de la Torre R, Farre M, Yubero-Lahoz S, Dziobek I, Van den Bos W, Ramaekers JG (2014) No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT 1a receptor activation. PLoS One 9:e100719

    Article  PubMed  PubMed Central  Google Scholar 

  • Mas M, Farré M, de la Torre R, Roset PN, Ortuño J, Segura J, Camí J (1999) Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. J Pharmacol Exp Ther 290:136–145

    CAS  PubMed  Google Scholar 

  • Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Doblin R (2011) The safety and efficacy of±3, 4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol 25:439–452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mithoefer M, Wagner M, Mithoefer A, Jerome L, Martin S, Yazar-Klosinski B (2013) Durability of improvement in PTSD symptoms and absence of harmful effects or drug dependency after MDMA-assisted psychotherapy: a prospective long-term follow-up study. J Psychopharmacol 27:28–39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morean ME, de Wit H, King AC, Sofuoglu M, Rueger SY, O’Malley SS (2013) The drug effects questionnaire: psychometric support across three drug types. Psychopharmacology 227:177–192

    Article  CAS  PubMed  Google Scholar 

  • Oehen P, Traber R, Widmer V, Schnyder U (2013) A randomized, controlled pilot study of MDMA (±3, 4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic post-traumatic stress disorder (PTSD). J Psychopharmacol 27:40–52

    Article  CAS  PubMed  Google Scholar 

  • Parrott AC (2001) Human psychopharmacology of ecstasy (MDMA): a review of 15 years of empirical research. Hum Psychopharmacol Clin Exp 16:557–577

    Article  CAS  Google Scholar 

  • Parrott AC (2004) MDMA (3, 4-Methylenedioxymethamphetamine) or ecstasy: the neuropsychobiological implications of taking it at dances and raves. Neuropsychobiology 50:329–335

    Article  CAS  PubMed  Google Scholar 

  • Parrott AC (2009) Cortisol and 3,4-methylenedioxymethamphetamine: neurohormonal aspects of bioenergetic stress in ecstasy users. Neuropsychobiology 60:148–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parrott AC, Lock J, Adnum L, Thome J (2013) MDMA can increase cortisol levels by 800% in dance clubbers. J Psychopharmacol 27:113–114

    Article  PubMed  Google Scholar 

  • Parrott AC, Montgomery C, Wetherell MA, Downey LA, Stough C, Scholey AB (2014) MDMA, cortisol, and heightened stress in recreational ecstasy users. Behav Pharmacol 25:458–472

    CAS  PubMed  Google Scholar 

  • Rodgers J, Buchanan T, Pearson C, Parrott AC, Ling J, Heffernan T, Scholey AB (2006) Differential experiences of the psychobiological sequelae of ecstasy use: quantitative and qualitative data from an internet study. J Psychopharmacol 20:437–446

    Article  PubMed  Google Scholar 

  • Schmid Y, Hysek CM, Simmler LD, Crockett MJ, Quednow BB, Liechti ME (2014) Differential effects of MDMA and methylphenidate on social cognition. J Psychopharmacol 28:847–856

    Article  CAS  PubMed  Google Scholar 

  • Seibert J, Hysek CM, Penno CA, Schmid Y, Kratschmar DV, Liechti ME, Odermatt A (2014) Acute effects of 3, 4-methylenedioxymethamphetamine and methylphenidate on circulating steroid levels in healthy subjects. Neuroendocrinology 100:17–25

    Article  CAS  PubMed  Google Scholar 

  • Thompson M, Callaghan P, Hunt G, Cornish J, McGregor I (2007) A role for oxytocin and 5-HT1A receptors in the prosocial effects of 3, 4 methylenedioxymethamphetamine (“ecstasy”). Neuroscience 146:509–514

    Article  CAS  PubMed  Google Scholar 

  • Torre R, Farre M, Roset P, López CH, Mas M, Ortuno J, Menoyo E, Pizarro N, Segura J, Cami J (2000) Pharmacology of MDMA in humans. Ann N Y Acad Sci 914:225–237

    Article  PubMed  Google Scholar 

  • Vollenweider FX, Gamma A, Liechti M, Huber T (1998) Psychological and cardiovascular effects and short-term sequelae of MDMA (“ecstasy”) in MDMA-naive healthy volunteers. Neuropsychopharmacology 19:241–251

    Article  CAS  PubMed  Google Scholar 

  • Wardle MC, de Wit H (2014) MDMA alters emotional processing and facilitates positive social interaction. Psychopharmacology 231:4219–4229

  • Wardle MC, Kirkpatrick MG, de Wit H (2014) ‘Ecstasy’as a social drug: MDMA preferentially affects responses to emotional stimuli with social content. Soc Cogn Affect Neurosci 9:1076–1081

    Article  PubMed  PubMed Central  Google Scholar 

  • White TL, Justice AJ, de Wit H (2002) Differential subjective effects of D-amphetamine by gender, hormone levels and menstrual cycle phase. Pharmacol Biochem Behav 73:729–741

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Harriet de Wit.

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Funding

This research was supported by DA02812. M.A.M was supported by a National Institute of Mental Health training grant (T32 MH020065) and A.K.B. was supported by a training grant from the National Institute of General Medical Sciences (T32 GM007281).

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The authors declare that they have no conflicts of interest.

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Bershad, A.K., Miller, M.A. & de Wit, H. MDMA does not alter responses to the Trier Social Stress Test in humans. Psychopharmacology 234, 2159–2166 (2017). https://doi.org/10.1007/s00213-017-4621-x

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  • DOI: https://doi.org/10.1007/s00213-017-4621-x

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