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S.23.01 Effects of MDMA on sociability and neural response to social threat and social reward
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S.23. MDMA (ecstasy) and the neurobiology of prosocial behaviour
S.23. MDMA (ecstasy) and the neurobiology of prosocial behaviour S.23.01 Effects of MDMA on sociability and neural response to social threat and social reward H. de Wit1 ° , G. Bedi1 , L. Phan1 , M. Kirkpatrick1 . 1 The University of Chicago, Department of Psychiatry, Chicago, USA MDMA (±3,4-methylenedioxymethamphetamine, ‘ecstasy’) reportedly increases feelings of empathy, sociability, and interpersonal closeness, feelings that may contribute to both recreational and therapeutic use of the drug. We have conducted three studies examining the acute behavioral and neural effects of oral MDMA in healthy young adults. Study 1 [1]: Volunteers received MDMA (0.75, 1.5 mg/kg), methamphetamine (20 mg; METH), and placebo before viewing images of emotional facial expressions and vocal cues. MDMA (1.5 mg/kg) impaired recognition of fearful and sad facial expressions without affecting positive emotions, and it marginally impaired identification of sad vocal expressions. Both MDMA and METH increased feelings of sociability and playfulness, but only MDMA (1.5 mg/kg) enhanced feelings of lovingness and friendliness. Study 2 [2]: Using fMRI, this study examined the effect of MDMA on brain activation while viewing images of emotional facial expressions. MDMA attenuated brain response to angry expressions in the left amygdala and enhanced response to happy expressions in the ventral striatum. Study 3: This study further examined effects of MDMA, in participants tested under solitary conditions. MDMA increased feelings of both sociability and loneliness. Additionally, when given the choice to socialize, the drug increased preference for being with others. Taken together, these findings confirm previous reports that MDMA increases feelings of sociability, and suggest that it may produce these feelings by reducing sensitivity to negative emotional signals in others, rather than by increasing ‘empathy’. This property of the drug may contribute to both its abuse potential and its potential for psychotherapeutic use. References [1] Bedi, G., D. Hyman, H. de Wit (2010). Is ecstasy an ‘empathogen’? MDMA increases social feelings but blunts identification of negative emotions in others. Biological Psychiatry, 68, 1134−40. PMC2997873. [2] Bedi, G, K.L. Phan, M. Angstadt, H. de Wit (2009) Effects of MDMA on sociability and neural response to social threat and social reward. Psychopharmacology 207(1): 73−83 PMID: 19680634.
S.23.02 Empathy and aggression; two faces of ecstasy?
Following a brief review of naturalistic studies of changes in self-rated measures of aggression, the focus will be on studies using cognitive assessments of aggression which indirectly probe biases in information processing. These have compared ecstasy users with a range of other groups (non-users; polydrug users; ex-MDMA users). The findings were that ecstasy users score significantly lower than controls shortly after acute ingestion, significantly higher 3 to 4 days later but do not differ after at least 7 days. Further this sub-acute interpretative bias is seen in both male and female users and correlates positively with degree of ecstasy use. This pattern contrasts with current and ex-opiate users who show a significantly greater bias than controls away from aggressive and towards neutral interpretations. References [1] Mithoefer et al (2010) J Psychopharmacol. doi:10.1177/0269881110378371.
S.23.03 Effects of ecstasy consumption on water homeostasis and secretion of vasopressin and oxytocin: a pharmacogenetic study K. Wolff1 ° , E.M. Tsapakis2 , M.L. Forsling3 , K.J. Aitchison2 . 1 King’s College London, Addiction Department, London, United Kingdom; 2 King’s College London, MRC Unit Social Genetic & Developmental Psychiatry, London, United Kingdom; 3 King’s College London, School Medicine, London, United Kingdom The physiological effects of Ecstasy (‘E’, MDMA) whilst clubbing include elevated body temperature, profuse sweating and inadequate hydration [1]. Ingestion of large amounts of water to avoid overheating has been reported to be partly responsible for hyponatraemia observed in clubbers. Our research has shown [2] that the fundamental mechanism behind the induction of hyponatraemia in ‘E’ users is inappropriate antidiuretic hormone (ADH) secretion. This paper reports an association between genotypes of two candidate polymorphic enzymes CYP2D6 and COMT involved in the metabolism of MDMA, and the potential for induction of hyponatremia. MDMA toxicity may be determined by poor metabolism (PM), with CYP2D6 being responsible for demethylenation, and catechol-O-methyl transferase (COMT) for O-methylation. Blood was obtained from 30 Caucasian (17 male) experienced clubbers. Pre- and post-clubbing measurements were performed to compare biochemical indices. MDMA ingestion Table 1. CYP2D6 genotype and allele frequencies according to use of ecstasy (E status) post-‘clubbing’ MDMA urinalysis. E status
CYP2D6 metabolic status
Frequency (%)
Used
EM/EM [*1/*2] EM/IM [*1/*10, *2/*35, *2/*41, *2/*9] EM/PM [*1/*3, *1/*4, *1/*6] IM/IM [*41/*41] PM/IM [*5/*41]
Not used
EM/EM [*1/*1, *2/*2, *35/*35, *35/*41] EM/IM [*1/*35, *1/*41] EM/PM [*1/*3, *1/*4, *1/*5] PM/IM [*4/*35, *6/*41] PM/EM [*4/*29] PM/PM [*4/*4]
4 (21.1) 4 (21.1) 9 (47.4) 1 (5.3) 1 (5.3) 19 (100.00) 7 (26.9) 5 (19.2) 8 (30.8) 2 (7.7) 1 (3.8) 3 (11.5) 26 (100.00)
H. Curran1 ° , R. Hoshi1 . 1 University College London, Clinical health Psychology, London, United Kingdom MDMA (+3,4-methylenedioxymethamphetamine; “ecstasy,”) is often termed an ‘empathogen’ to reflect its acute subjective effects: feelings of empathy, friendliness and closeness to others. Such effects underpin recent studies [1] evaluating its clinical use as an acute adjunct to psychological treatments of anxiety disorders. An acute dose of MDMA can release around 80% of central serotonin stores, and this, combined with inhibition of tryptophan hydroxylase, means that attenuation of central 5-HT can persist for days after (Green et al 2003). Serotonin has been implicated in modulating a range of human functions, including aggression and mood. Lowered 5-HT after taking MDMA could therefore be associated with increased aggression as well as depression.
Key: EM, extensive metaboliser; IM, intermediate metaboliser; PM, poor metaboliser.
S.23. MDMA (ecstasy) and the neurobiology of prosocial behaviour
S.23. MDMA (ecstasy) and the neurobiology of prosocial behaviour S.23.01 Effects of MDMA on sociability and neural response to social threat and social reward H. de Wit1 ° , G. Bedi1 , L. Phan1 , M. Kirkpatrick1 . 1 The University of Chicago, Department of Psychiatry, Chicago, USA MDMA (±3,4-methylenedioxymethamphetamine, ‘ecstasy’) reportedly increases feelings of empathy, sociability, and interpersonal closeness, feelings that may contribute to both recreational and therapeutic use of the drug. We have conducted three studies examining the acute behavioral and neural effects of oral MDMA in healthy young adults. Study 1 [1]: Volunteers received MDMA (0.75, 1.5 mg/kg), methamphetamine (20 mg; METH), and placebo before viewing images of emotional facial expressions and vocal cues. MDMA (1.5 mg/kg) impaired recognition of fearful and sad facial expressions without affecting positive emotions, and it marginally impaired identification of sad vocal expressions. Both MDMA and METH increased feelings of sociability and playfulness, but only MDMA (1.5 mg/kg) enhanced feelings of lovingness and friendliness. Study 2 [2]: Using fMRI, this study examined the effect of MDMA on brain activation while viewing images of emotional facial expressions. MDMA attenuated brain response to angry expressions in the left amygdala and enhanced response to happy expressions in the ventral striatum. Study 3: This study further examined effects of MDMA, in participants tested under solitary conditions. MDMA increased feelings of both sociability and loneliness. Additionally, when given the choice to socialize, the drug increased preference for being with others. Taken together, these findings confirm previous reports that MDMA increases feelings of sociability, and suggest that it may produce these feelings by reducing sensitivity to negative emotional signals in others, rather than by increasing ‘empathy’. This property of the drug may contribute to both its abuse potential and its potential for psychotherapeutic use. References [1] Bedi, G., D. Hyman, H. de Wit (2010). Is ecstasy an ‘empathogen’? MDMA increases social feelings but blunts identification of negative emotions in others. Biological Psychiatry, 68, 1134−40. PMC2997873. [2] Bedi, G, K.L. Phan, M. Angstadt, H. de Wit (2009) Effects of MDMA on sociability and neural response to social threat and social reward. Psychopharmacology 207(1): 73−83 PMID: 19680634.
S.23.02 Empathy and aggression; two faces of ecstasy?
Following a brief review of naturalistic studies of changes in self-rated measures of aggression, the focus will be on studies using cognitive assessments of aggression which indirectly probe biases in information processing. These have compared ecstasy users with a range of other groups (non-users; polydrug users; ex-MDMA users). The findings were that ecstasy users score significantly lower than controls shortly after acute ingestion, significantly higher 3 to 4 days later but do not differ after at least 7 days. Further this sub-acute interpretative bias is seen in both male and female users and correlates positively with degree of ecstasy use. This pattern contrasts with current and ex-opiate users who show a significantly greater bias than controls away from aggressive and towards neutral interpretations. References [1] Mithoefer et al (2010) J Psychopharmacol. doi:10.1177/0269881110378371.
S.23.03 Effects of ecstasy consumption on water homeostasis and secretion of vasopressin and oxytocin: a pharmacogenetic study K. Wolff1 ° , E.M. Tsapakis2 , M.L. Forsling3 , K.J. Aitchison2 . 1 King’s College London, Addiction Department, London, United Kingdom; 2 King’s College London, MRC Unit Social Genetic & Developmental Psychiatry, London, United Kingdom; 3 King’s College London, School Medicine, London, United Kingdom The physiological effects of Ecstasy (‘E’, MDMA) whilst clubbing include elevated body temperature, profuse sweating and inadequate hydration [1]. Ingestion of large amounts of water to avoid overheating has been reported to be partly responsible for hyponatraemia observed in clubbers. Our research has shown [2] that the fundamental mechanism behind the induction of hyponatraemia in ‘E’ users is inappropriate antidiuretic hormone (ADH) secretion. This paper reports an association between genotypes of two candidate polymorphic enzymes CYP2D6 and COMT involved in the metabolism of MDMA, and the potential for induction of hyponatremia. MDMA toxicity may be determined by poor metabolism (PM), with CYP2D6 being responsible for demethylenation, and catechol-O-methyl transferase (COMT) for O-methylation. Blood was obtained from 30 Caucasian (17 male) experienced clubbers. Pre- and post-clubbing measurements were performed to compare biochemical indices. MDMA ingestion Table 1. CYP2D6 genotype and allele frequencies according to use of ecstasy (E status) post-‘clubbing’ MDMA urinalysis. E status
CYP2D6 metabolic status
Frequency (%)
Used
EM/EM [*1/*2] EM/IM [*1/*10, *2/*35, *2/*41, *2/*9] EM/PM [*1/*3, *1/*4, *1/*6] IM/IM [*41/*41] PM/IM [*5/*41]
Not used
EM/EM [*1/*1, *2/*2, *35/*35, *35/*41] EM/IM [*1/*35, *1/*41] EM/PM [*1/*3, *1/*4, *1/*5] PM/IM [*4/*35, *6/*41] PM/EM [*4/*29] PM/PM [*4/*4]
4 (21.1) 4 (21.1) 9 (47.4) 1 (5.3) 1 (5.3) 19 (100.00) 7 (26.9) 5 (19.2) 8 (30.8) 2 (7.7) 1 (3.8) 3 (11.5) 26 (100.00)
H. Curran1 ° , R. Hoshi1 . 1 University College London, Clinical health Psychology, London, United Kingdom MDMA (+3,4-methylenedioxymethamphetamine; “ecstasy,”) is often termed an ‘empathogen’ to reflect its acute subjective effects: feelings of empathy, friendliness and closeness to others. Such effects underpin recent studies [1] evaluating its clinical use as an acute adjunct to psychological treatments of anxiety disorders. An acute dose of MDMA can release around 80% of central serotonin stores, and this, combined with inhibition of tryptophan hydroxylase, means that attenuation of central 5-HT can persist for days after (Green et al 2003). Serotonin has been implicated in modulating a range of human functions, including aggression and mood. Lowered 5-HT after taking MDMA could therefore be associated with increased aggression as well as depression.
Key: EM, extensive metaboliser; IM, intermediate metaboliser; PM, poor metaboliser.