3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) increases sociability. The prosocial effects of MDMA may result from the release of the “social hormone” oxytocin and associated alterations in the processing of socioemotional stimuli.
Materials and methods
We investigated the effects of MDMA (125 mg) on the ability to infer the mental states of others from social cues of the eye region in the Reading the Mind in the Eyes Test. The study included 48 healthy volunteers (24 men, 24 women) and used a double-blind, placebo-controlled, within-subjects design. A choice reaction time test was used to exclude impairments in psychomotor function. We also measured circulating oxytocin and cortisol levels and subjective drug effects.
MDMA differentially affected mind reading depending on the emotional valence of the stimuli. MDMA enhanced the accuracy of mental state decoding for positive stimuli (e.g., friendly), impaired mind reading for negative stimuli (e.g., hostile), and had no effect on mind reading for neutral stimuli (e.g., reflective). MDMA did not affect psychomotor performance, increased circulating oxytocin and cortisol levels, and produced subjective prosocial effects, including feelings of being more open, talkative, and closer to others.
The shift in the ability to correctly read socioemotional information toward stimuli associated with positive emotional valence, together with the prosocial feelings elicited by MDMA, may enhance social approach behavior and sociability when MDMA is used recreationally and facilitate therapeutic relationships in MDMA-assisted psychotherapeutic settings.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Anavekar SN, Jarrott B, Toscano M, Louis WJ (1982) Pharmacokinetic and pharmacodynamic studies of oral clonidine in normotensive subjects. Eur J Clin Pharmacol 23:1–5
Baron-Cohen S, Wheelwright S, Hill J, Raste Y, Plumb I (2001) The "Reading the Mind in the Eyes" Test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism. J Child Psychol Psychiatry 42:241–251
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 (Berl) 207:73–83
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
Bopp G, Bender W, Schütz CG (2005) Validierung der deutschen Version des Addiction Research Center Inventory (ARCI). Suchtmedizin 7:152–153
Broadbear JH, Tunstall B, Beringer K (2011) Examining the role of oxytocin in the interoceptive effects of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") using a drug discrimination paradigm in the rat. Addict Biol 16:202–214
Derogatis LR, Rickels K, Rock AF (1976) The SCL-90 and the MMPI: a step in the validation of a new self-report scale. Br J Psychiatry 128:280–289
Di Simplicio M, Massey-Chase R, Cowen PJ, Harmer CJ (2009) Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers. J Psychopharmacol 23:241–248
Domes G, Heinrichs M, Glascher J, Buchel C, Braus DF, Herpertz SC (2007a) Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry 62:1187–1190
Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC (2007b) Oxytocin improves "mind-reading" in humans. Biol Psychiatry 61:731–733
Domes G, Lischke A, Berger C, Grossmann A, Hauenstein K, Heinrichs M, Herpertz SC (2010) Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology 35:83–93
Dumont GJ, Sweep FC, van der Steen R, Hermsen R, Donders AR, Touw DJ, van Gerven JM, Buitelaar JK, Verkes RJ (2009) Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration. Soc Neurosci 4:359–366
Fahrenberg J, Hampel R, Selg H (1984) Das Freiburger Persönlichkeitsinventar (FPI). Hogrefe, Göttingen, Germany
Farre M, Abanades S, Roset PN, Peiro AM, Torrens M, O'Mathuna B, Segura M, de la Torre R (2007) Pharmacological interaction between 3,4-methylenedioxymethamphetamine (ecstasy) and paroxetine: pharmacological effects and pharmacokinetics. J Pharmacol Exp Ther 323:954–962
Fertuck EA, Jekal A, Song I, Wyman B, Morris MC, Wilson ST, Brodsky BS, Stanley B (2009) Enhanced 'Reading the Mind in the Eyes' in borderline personality disorder compared to healthy controls. Psychol Med 39:1979–1988
Forsling ML, Fallon JK, Shah D, Tilbrook GS, Cowan DA, Kicman AT, Hutt AJ (2002) The effect of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and its metabolites on neurohypophysial hormone release from the isolated rat hypothalamus. Br J Pharmacol 135:649–656
Guastella AJ, Mitchell PB, Mathews F (2008) Oxytocin enhances the encoding of positive social memories in humans. Biol Psychiatry 64:256–258
Guastella AJ, Einfeld SL, Gray KM, Rinehart NJ, Tonge BJ, Lambert TJ, Hickie IB (2010) Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry 67:692–694
Harkness KL, Sabbagh MA, Jacobson JA, Chowdrey NK, Chen T (2005) Enhanced accuracy of mental state decoding in dysphoric college students. Cogn Emotion 19:999–1025
Harris DS, Baggott M, Mendelson JH, Mendelson JE, Jones RT (2002) Subjective and hormonal effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berl) 162:396–405
Haschke M, Suter K, Hofmann S, Witschi R, Frohlich J, Imanidis G, Drewe J, Briellmann TA, Dussy FE, Krahenbuhl S, Surber C (2010) Pharmacokinetics and pharmacodynamics of nasally delivered midazolam. Br J Clin Pharmacol 69:607–616
Hurlemann R, Patin A, Onur OA, Cohen MX, Baumgartner T, Metzler S, Dziobek I, Gallinat J, Wagner M, Maier W, Kendrick KM (2010) Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans. J Neurosci 30:4999–5007
Hysek CM, Simmler LD, Ineichen M, Grouzmann E, Hoener MC, Brenneisen R, Huwyler J, Liechti ME (2011) The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA ("ecstasy") in humans. Clin Pharmacol Ther 90:246–255
Hysek CM, Brugger R, Simmler LD, Bruggisser M, Doncelli M, Grouzmann E, Hoener MC, Liechti ME (2012) Effects of the α2-adrenergic agonist clonidine on the pharmacodynamics and pharmacokinetics of methylenedioxymethamphetamine in healthy volunteers. J Pharmacol Exp Ther 340:286–294
Johansen PO, Krebs TS (2009) How could MDMA (ecstasy) help anxiety disorders? A neurobiological rationale. J Psychopharmacol 23:389–391
Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A (2005) Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci 25:11489–11493
Knutson B, Cooper JC (2005) Functional magnetic resonance imaging of reward prediction. Curr Opin Neurol 18:411–417
Landgraf R, Neumann I, Holsboer F, Pittman QJ (1995) Interleukin-1β stimulates both central and peripheral release of vasopressin and oxytocin in the rat. Eur J Neurosci 7:592–598
Liechti ME, Vollenweider FX (2000) The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3,4-methylenedioxymethamphetamine ('ecstasy') in healthy volunteers. J Psychopharmacol 14:269–274
Liechti ME, Baumann C, Gamma A, Vollenweider FX (2000) Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") are attenuated by the serotonin uptake inhibitor citalopram. Neuropsychopharmacology 22:513–521
Liechti ME, Gamma A, Vollenweider FX (2001) Gender differences in the subjective effects of MDMA. Psychopharmacology (Berl) 154:161–168
Marsh AA, Yu HH, Pine DS, Blair RJ (2010) Oxytocin improves specific recognition of positive facial expressions. Psychopharmacology (Berl) 209:225–232
Martin WR, Sloan JW, Sapira JD, Jasinski DR (1971) Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther 12:245–258
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-methylenedioxymethamphetamine in humans. J Pharmacol Exp Ther 290:136–145
Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M (2011) Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci 12:524–538
Mithoefer MC, Wagner MT, Mithoefer AT, Jerome I, Doblin R (2010) 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
Neumann ID (2008) Brain oxytocin: a key regulator of emotional and social behaviours in both females and males. J Neuroendocrinol 20:858–865
Nieuwenhuis S, van Nieuwpoort IC, Veltman DJ, Drent ML (2007) Effects of the noradrenergic agonist clonidine on temporal and spatial attention. Psychopharmacology (Berl) 193:261–269
Roelands B, Goekint M, Heyman E, Piacentini MF, Watson P, Hasegawa H, Buyse L, Pauwels F, De Schutter G, Meeusen R (2008) Acute norepinephrine reuptake inhibition decreases performance in normal and high ambient temperature. J Appl Physiol 105:206–212
Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS (2001) Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39:32–41
Schachinger H, Cox D, Linder L, Brody S, Keller U (2003) Cognitive and psychomotor function in hypoglycemia: response error patterns and retest reliability. Pharmacol Biochem Behav 75:915–920
Schmitz N, Hartkamp N, Kiuse J, Franke GH, Reister G, Tress W (2000) The Symptom Check-List-90-R (SCL-90-R): a German validation study. Qual Life Res 9:185–193
Schulze L, Lischke A, Greif J, Herpertz SC, Heinrichs M, Domes G (2011) Oxytocin increases recognition of masked emotional faces. Psychoneuroendocrinology 36:1378–1382
Simmler LD, Hysek CM, Huwyler J, Liechti ME (2011a) Duloxetine prevents 3,4-methylenedioxymethamphetamine-induced serotonin release in vitro and psychostimulant effects in healthy subjects. Eur Neuropsychopharmacol 21(S3):S262
Simmler LD, Hysek CM, Liechti ME (2011b) Sex differences in the effects of MDMA (ecstasy) on plasma copeptin in healthy subjects. J Clin Endocrinol Metab 96:2844–2850
Smeets T, Dziobek I, Wolf OT (2009) Social cognition under stress: differential effects of stress-induced cortisol elevations in healthy young men and women. Horm Behav 55:507–513
Spielberger CD, Gorsuch RC, Lusheme RE (1970) Manual for the Stait Trait Anxiety Inventory. Consulting Psychologists Press, Palo Alto
Tancer M, Johanson CE (2007) The effects of fluoxetine on the subjective and physiological effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology 189:565–573
Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS (2007) A role for oxytocin and 5-HT1A receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy"). Neuroscience 146:509–514
Thompson MR, Hunt GE, McGregor IS (2009) Neural correlates of MDMA ("ecstasy")-induced social interaction in rats. Soc Neurosci 4:60–72
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
Wittchen HU, Wunderlich U, Gruschwitz S, Zaudig M (1997) SKID-I: Strukturiertes Klinisches Interview für DSM-IV. Hogrefe, Göttingen
Wolff K, Tsapakis EM, Winstock AR, Hartley D, Holt D, Forsling ML, Aitchison KJ (2006) Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population. J Psychopharmacol 20:400–410
Zald DH (2003) The human amygdala and the emotional evaluation of sensory stimuli. Brain Res Brain Res Rev 41:88–123
We thank R. Brugger, V. Nicola, C. Bläsi, S. Müller, and S. Purschke for their assistance in study management and M. Arends for editorial assistance. This work was supported by the Swiss National Science Foundation (grant no. 323230_126231) and University of Basel (grant no. DPH2037).
Conflict of interest
The authors report no biomedical financial interest or potential conflict of interest.
About this article
Cite this article
Hysek, C.M., Domes, G. & Liechti, M.E. MDMA enhances “mind reading” of positive emotions and impairs “mind reading” of negative emotions. Psychopharmacology 222, 293–302 (2012). https://doi.org/10.1007/s00213-012-2645-9
- Social cognition
- Face recognition