±3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) reportedly produces unique subjective effects, including increased sociability, feelings of closeness with others, and reduced interpersonal defensiveness. Despite their apparent importance in recreational and potential psychotherapeutic use of MDMA, the defining characteristics and neurobiological mechanisms of these interpersonal effects are poorly understood.
Materials and methods
We investigated acute effects of MDMA on self-reported sociability and neuronal activation in response to socially threatening (angry and fearful faces) and socially rewarding (happy faces) stimuli. Assessment of social threat response focused on amygdala activation, whereas assessment of social reward focused on ventral striatum activation. Healthy volunteers (N = 9) reporting past ecstasy use completed three experimental sessions, receiving MDMA (0.75 and 1.5 mg/kg) and placebo (PBO) under double-blind conditions. During peak drug effects, participants underwent functional magnetic resonance imaging while viewing standardized images depicting emotional facial expressions including angry, fearful, happy, and neutral expressions. They also completed standardized self-report measures of sociability.
MDMA (1.5 mg/kg) increased self-reported sociability compared to MDMA (0.75 mg/kg) and PBO. MDMA (1.5 mg/kg) attenuated left amygdala response to angry facial expressions compared to PBO, but MDMA did not affect amygdala reactivity to fearful expressions. MDMA (0.75 mg/kg) enhanced ventral striatum response to happy expressions relative to PBO.
These data present the first evidence that MDMA may increase sociability in humans both by diminishing responses to threatening stimuli and enhancing responses to rewarding social signals.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Anderson IM, Del-Ben CM, Mckie S, Richardson P, Williams SR, Elliott R et al (2007) Citalopram modulation of neuronal responses to aversive face emotions: a functional MRI study. Neuro Report 18:1351–1355
APA (1994) DSM-IV: diagnostic and statistical manual of mental disorders. American Psychiatric Association, MD
Bedi G, Redman J (2008) Ecstasy use and higher-level cognitive function: weak effects of ecstasy after control for potential confounds. Psychol Med 38:1319–1330
Cami J, Farre M, Mas M, Roset PN, Poudevida S, Mas A et al (2000) Human pharmacology of 3, 4-methylenedioxymethamphetamine (“Ecstasy”): psychomotor performance and subjective effects. J Clin Psychopharmacol 20:455–466
Cohen Z, Bonvento G, Lacombe P, Hamel E (1996) Serotonin in the regulation of brain microcirculation. Prog Neurobiol 50:335–362
Cole JC, Bailey M, Sumnall HR, Wagstaff GF, King LA (2002) The content of ecstasy tablets: implications for the study of their long-term effects. Addiction 97:1531–1536
Del-Ben CM, Deakin JFW, McKie S, Delvai NA, Williams SR, Elliot R et al (2005) The effect of citalopram pretreatment on neuronal responses to neuropsychological tasks in normal volunteers: an fMRI study. Neuropsychopharmacology 30:1724–1734
Del-Ben CM, Ferreira CAQ, Alves-Neto WC, Graeff FG (2008) Serotonergic modulation of face-emotion recognition. Braz J Med Biol Res 41:63–69
Douglas LA, Varlinskaya EI, Spear LP (2004) Rewarding properties of social interactions in adolescent and adult male and female rats: impact of social versus isolate housing of subjects and partners. Dev Psychobiol 45:153–162
Dumont GJH, Verkes RJ (2006) A review of acute effects of 3, 4-methylenedioxymethamphetmine in healthy volunteers. J Psychopharmacol 20:176–187
Ekman P, Friesen WV (1976) Pictures of facial affect. Consulting Psychologists, Palo Alto
Fitzgerald DA, Angstadt M, Jelsone LM, Nathan PJ, Phan KL (2006) Beyond threat: amygdala reactivity across multiple expressions of facial affect. NeuroImage 30:1441–1448
Folstein MF, Luria R (1973) Reliability, validity, and clinical application of the visual analog mood scale. Psychol Med 3:479–486
Friston KJ, Holmes AP, Worsley KJ, Poline JB, Frith CD, Frackowiak RS (1995) Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp 2:189–210
Gamma A, Buck A, Berthold T, Hell D, Vollenweider FX (2000) 3, 4-Methylenedioxymethamphetamine (MDMA) modulates cortical and limbic brain activity as measured by [H215O]-PET in healthy humans. Neuropsychopharmacology 23:388–395
Gilman JM, Ramchandani VA, Davis MB, Bjjork JM, Hommer DW (2008) Why we like to drink: a functional magnetic resonance imaging study of the rewarding and anxiolytic effects of alcohol. J Neurosci 28:4583–4591
Green AR, Mechan AO, Elliott JM, O’Shea E, Colado MI (2003) The pharmacology and clinical pharmacology of 3, 4-methylenedioxymethamphetamine (MDMA, “Ecstasy”). Pharmacol Rev 55:463–508
Hariri AR, Mattay VS, Tessitore A, Fera F, Smith WG, Weinberger DR (2002) Dextroamphetamine modulates the response of the human amygdala. Neuropsychopharmacology 27:1036–1040
Harmer CJ, Makcay CE, Reid CB, Cowen PJ, Goodwin GM (2006) Antidepressant drug treatment modifies the neural processing of nonconscious threat cues. Biol Psychiatry 59:816–820
Harris DS, Baggott M, Mendelson JH, Mendelson JE, Jones RT (2002) Subjective and hormonal effects of 3, 4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology 162(4):396–405
Holmes AP, Friston KJ (1998) Generalisability, random effects and population inference. NeuroImage 7:S754
Johanson CE, Uhlenhuth EH (1980) Drug preference and mood in humans: diazepam. Psychopharmacology 71:269–273
Johanson CE, Kilbey M, Gatchalian K, Tancer M (2006) Discriminative stimulus effects of 3, 4-methylenedioxymethamphetamine (MDMA) in humans trained to discriminate among d-amphetamine, meta-chlorophenylpiperazine and placebo. Drug Alcohol Depend 81:27–36
Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S et al (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
Kolbrich EA, Goodwin RS, Gorelick DA, Hayes RJ, Stein EA, Huestis MA (2008) Physiological and subjective responses to controlled oral 3, 4-methylenedioxymethamphetamine administration. J Clin Psychopharmacol 28:432–440
Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature 435:673–676
Liechti ME, Vollenweider FX (2000) Acute psychological and physiological effects of MDMA (“Ecstasy”) after haloperidol pretreatment in healthy humans. Eur Neuropsychopharmacol 10(4):289–295
Liechti ME, Saur MR, Gamma A, Hell D, Vollenweider FX (2000) Psychological and physiological effects of MDMA (“Ecstasy”) after pretreatment with the 5-HT-sub-2 antagonist ketanserin in healthy humans. Neuropsychopharmacology 23(4):396–404
McBride D, Barrett SP, Kelly JT, Aw A, Dagher A (2006) Effects of expectancy and abstinence on the neural response to smoking cues in cigarette smokers: an fMRI study. Neuropsychopharmacology 31:2728–2738
McCann UD, Eligulashvili V, Ricaurte GA (2000) ±3, 4-Methylenedioxymethamphetamine (‘Ecstasy’)-induced serotonin neurotoxicity: clinical studies. Neuropsychobiology 42:11–16
McGregor IS, Callaghan PD, Hunt GE (2008) From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use? Br J Pharmacol 154:358–368
McNair DLM, Droppleman L (1971). Profile of mood states. Educational and Industrial Testing Service: San Diego
Mechan A, Yuan J, Hatzidimitriou G, Irvine RJ, McCann UD, Ricaurte GA (2005) Pharmacokinetic profile of single and repeated oral doses of MDMA in squirrel monkeys: relationship to lasting effects on brain serotonin neurons. Neuropsychopharmacology 31:339–350
Meyer-Lindenberg A, Hariri AR, Munoz KE, Mervis CB, Mattay VS, Morris CA et al (2005) Neural correlates of genetically abnormal social cognition in William’s syndrome. Nat Neurosci 8:991–993
Morley KC, Arnold JC, McGregor IS (2005) Serotonin (1A) receptor involvement in acute 3, 4-methylenedioxymethamphetamine (MDMA) facilitation of social interaction in the rat. Prog Neuro-Psychopharmacol Biol Psychiatry 29:648–657
Parrott A (2007) The psychotherapeutic potential of MDMA (3, 4-methylenedioxymethamphetamine): an evidence-based review. Psychopharmacology 191:181–193
Phan KL, Fitzgerald DA, Nathan PJ, Tancer ME (2006) Association between amygdala hyperactivity to harsh faces and severity of social anxiety in generalized social phobia. Biol Psychiatry 59:424–429
Phan KL, Angstadt M, Golden J, Onyewuenyi I, Popovska A, de Wit H (2008) Cannabinoid modulation of amygdala reactivity to social signals of threat in humans. J Neurosci 28:2313–2319
Ricaurte GA, DeLanney LE, Irwin I, Langston JW (1988) Toxic effects of MDMA on central serotonergic neurons in the primate: importance of route and frequency of administration. Brain Res 446:165–168
Schott BH, Minuzzi L, Krebs RM, Elmenhorst D, Lang M, Winz OH et al (2008) Mesolimbic functional magnetic resonance imaging activations during reward anticipation correlate with reward-related ventral striatum dopamine release. J Neurosci 28:14311–14319
Skuse DH, Gallagher L (2008) Dopaminergic-neuropeptide interactions in the social brain. Trends Cogn Sci 13:27–35
Sumnall HR, Cole JC, Jerome L (2006) The varieties of ecstatic experience: an exploration of the subjective experiences of ecstasy. J Psychopharmacol 20:670–682
Tancer ME, Johanson CE (2003) Reinforcing, subjective, and physiological effects of MDMA in humans: a comparison with d-amphetamine and mCPP. Drug Alcohol Depend 72(1):33–44
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
Thiele KJ, Okun AC, Neisewander JL (2008) Social reward-conditioned place preference: a model revealing an interaction between cocaine and social context rewards in rats. Drug Alcohol Depend 96:202–212
Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS (2007) A role for oxytocin and 5-HT(1A) 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
Tse WS, Bond AJ (2002) Serotonergic interventions affects both social dominance and affiliative behavior. Psychopharmacology 161:324–330
Tsukiura T, Cabeza R (2008) Orbitofrontal and hippocampal contributions to memory for face-name associations: the rewarding power of a smile. Neuropsychologia 46:2310–2319
Vollenweider FX, Remensberger S, Hell D, Geyer MA (1999) Opposite effects of 3, 4-methylenedioxymethamphetamine (MDMA) on sensorimotor gating in rats versus healthy humans. Psychopharmacology 143(4):365–372
Walter B, Blecker C, Kirsch P, Sammer G, Schlienle A, Stark R, et al (2003). MARINA: An easy to use tool for the creation of MAsks for Region of INterest Analyses. Paper presented at Ninth International Conference on Functional Mapping of the Human Brain New York, NY, June
Whalen PJ, Rauch SL, Etcoff NL, McInerney SC, Lee MB, Jenike MA (1998) Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge. J Neurosci 18:411–418
Wolff K, Tsapakis EM, Winstock AR, Hartley D, Holt D, Forsling ML et al (2006) Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population. J Psychopharmacol 20:400–410
Young SN, Leyton M (2002) The role of serotonin in human mood and social interaction: insight from altered tryptophan levels. Pharmacol Biochem Behav 71:857–865
Zald DH (2003) The human amygdala and the emotional evaluation of sensory stimuli. Brain Res Rev 41:88–123
Thanks to Gina Beguhn, David Hyman, Patricia Kriegal, Robert Lyons, and Rosemary McCarron for technical assistance; to Royce Lee for medical support; and Emmanuel Semmes for pharmaceutical support. Thanks also to participants. This research was supported by National Institute of Drug Abuse (DA02812).
Disclosures/conflict of interest
This experiment complied with the current laws of the country in which it was performed (USA).
About this article
Cite this article
Bedi, G., Phan, K.L., Angstadt, M. et al. Effects of MDMA on sociability and neural response to social threat and social reward. Psychopharmacology 207, 73–83 (2009). https://doi.org/10.1007/s00213-009-1635-z