Effects of MDMA on Social and Emotional Processing

The main aim of the study is to investigate the effects of ±3,4-methylenedioxymethamphetamine (MDMA; ecstasy) on social and emotional processing in healthy humans. Ecstasy is a widely used recreational drug, with over 2 million Americans reporting use of the drug in 2006. With this number of users, and evidence that high doses of MDMA are neurotoxic in laboratory animals, the public health implications of ecstasy use may be substantial. Certain subjective effects of this drug distinguish it from other stimulants, and may contribute to its widespread use: That is, users report that ecstasy produces profound feelings of empathy and closeness to others. These so-called 'empathogenic' effects, which may reflect the distinctive neurochemical profile of action of the drug, have yet to be characterized in controlled laboratory studies. The investigators propose to characterize the effects of MDMA on measures of social and emotional processing that may contribute to this 'empathogenic' profile, including measures of emotion recognition, emotional responsiveness and sociability. The investigators will assess effects of MDMA (0, 0.75 and 1.5 mg/kg up to 125 mg) one active control drug (oxytocin: 20 IU) in 100 volunteers who report some prior ecstasy use. Oxytocin will be used because it appears to produce pro-social behavioral effects resembling those attributed to MDMA.

Healthy volunteers received all drug conditions (MDMA, oxytocin, and placebo) using a within-subjects design.

This was a within-subjects, double-blind, double-dummy, placebo-controlled experiment during which each participant received a single dose of MDMA (0.75, 1.5 mg/kg) on two session, oxytocin (20 IU) as an active control on one session (see second Intervention), and placebo one session (see third intervention).

This was a within-subjects, double-blind, double-dummy, placebo-controlled experiment during which each participant received oxytocin (20 IU) on one session, MDMA on two sessions (see first Intervention), and placebo on one session (see third Intervention).

This was a within-subjects, double-blind, double-dummy, placebo-controlled experiment during which each participant received placebo on one session, MDMA on two sessions (see first Intervention), and oxytocin (20 IU) on one session (see second Intervention).

Participants complete the Dynamic Emotional Identification Task, or DEIT (Wardle et al. 2012) following MDMA, oxytocin or placebo administration during which they identify emotional facial expressions presented on the screen. Participants completed this task once during each of the sessions. In the DEIT, 10 actors performed angry, fearful, sad, and happy expressions, for a total of 40 sequences, which were presented in random order. Each sequence consisted of 50 "frames" progressing from 0 to 100% emotional intensity at 2% steps, producing a color video of an emotional expression developing. Participants were instructed to "press the space bar as soon as you know what expression is being displayed." This ended the sequence and presented options of "angry," "fearful," "sad," and "happy." Perception of expressions was quantified as the intensity (0-100 %) of the face when the participant pressed the space bar for correctly identified sequences.

Participants completed the Dynamic Emotional Identification Task, or DEIT (Wardle et al. 2012) following MDMA, oxytocin or placebo administration during which they identify emotional facial expressions presented on the screen. Participants completed this task once during each of the sessions. In the DEIT, 10 actors performed angry, fearful, sad, and happy expressions, for a total of 40 sequences, which were presented in random order. Each sequence consisted of 50 "frames" progressing from 0 to 100% emotional intensity at 2% steps, producing a color video of an emotional expression developing. Participants were instructed to "press the space bar as soon as you know what expression is being displayed." This ended the sequence and presented options of "angry," "fearful," "sad," and "happy." Perception of expressions was quantified as the intensity (0-100 %) of the face when the participant pressed the space bar for correctly identified sequences.

Participants completed the Dynamic Emotional Identification Task, or DEIT (Wardle et al. 2012) following MDMA, oxytocin or placebo administration during which they identify emotional facial expressions presented on the screen. Participants completed this task once during each of the sessions. In the DEIT, 10 actors performed angry, fearful, sad, and happy expressions, for a total of 40 sequences, which were presented in random order. Each sequence consisted of 50 "frames" progressing from 0 to 100% emotional intensity at 2% steps, producing a color video of an emotional expression developing. Participants were instructed to "press the space bar as soon as you know what expression is being displayed." This ended the sequence and presented options of "angry," "fearful," "sad," and "happy." Perception of expressions was quantified as the intensity (0-100 %) of the face when the participant pressed the space bar for correctly identified sequences.

Participants completed this visual analog questionnaire item during which participants selected a rating between 0 ("Not at all") to 100 ("Extremely"). Participants completed this questionnaire item before drug administration and every 30 minutes after drug administration at each session for a total of 6 times. Results are presented as the mean response over the entire session calculated as change from baseline.

Participants completed this visual analog questionnaire item during which participants selected a rating between 0 ("Not at all") to 100 ("Extremely"). Participants completed this questionnaire item before drug administration and every 30 minutes after drug administration at each session for a total of 6 times. Results are presented as the mean response over the entire session calculated as change from baseline.

Participants completed this visual analog questionnaire item during which participants selected a rating between 0 ("Not at all") to 100 ("Extremely"). Participants completed this questionnaire item before drug administration and every 30 minutes after drug administration at each session for a total of 6 times. Results are presented as the mean response over the entire session calculated as change from baseline.

Participants completed this visual analog questionnaire item during which participants selected a rating between 0 ("Not at all") to 100 ("Extremely"). Participants completed this questionnaire item before drug administration and every 30 minutes after drug administration at each session for a total of 6 times. Results are presented as the mean response over the entire session calculated as change from baseline.

Participants completed this visual analog questionnaire item during which participants selected a rating between 0 ("Not at all") to 100 ("Extremely"). Participants completed this questionnaire item before drug administration and every 30 minutes after drug administration at each session for a total of 6 times. Results are presented as the mean response over the entire session calculated as change from baseline.

Participants completed this visual analog questionnaire item during which participants selected a rating between 0 ("Not at all") to 100 ("Extremely"). Participants completed this questionnaire item before drug administration and every 30 minutes after drug administration at each session for a total of 6 times. Results are presented as the mean response over the entire session calculated as change from baseline.

Participants completed this visual analog questionnaire item during which participants selected a rating between 0 ("Not at all") to 100 ("Extremely"). Participants completed this questionnaire item before drug administration and every 30 minutes after drug administration at each session for a total of 6 times. Results are presented as the mean response over the entire session calculated as change from baseline.

Participants completed this visual analog questionnaire item during which participants selected a rating between 0 ("Not at all") to 100 ("Extremely"). Participants completed this questionnaire item before drug administration and every 30 minutes after drug administration at each session for a total of 6 times. Results are presented as the mean response over the entire session calculated as change from baseline.

Participants completed this visual analog questionnaire item during which participants selected a rating between 0 ("Not at all") to 100 ("Extremely"). Participants completed this questionnaire item before drug administration and every 30 minutes after drug administration at each session for a total of 6 times. Results are presented as the mean response over the entire session calculated as change from baseline.

Heart rate (bpm) was assessed before drug administration and repeatedly after drug administration for the each session. Results are presented as the mean response over the entire session calculated as change from baseline.

Heart rate (bpm) was assessed before drug administration and repeatedly after drug administration for the each session. Results are presented as the mean response over the entire session calculated as change from baseline.

Heart rate (bpm) was assessed before drug administration and repeatedly after drug administration for the each session. Results are presented as the mean response over the entire session calculated as change from baseline.

Systolic Blood Pressure (mmHg) was assessed before drug administration and repeatedly after drug administration for the each session. Results are presented as the mean response over the entire session calculated as change from baseline.

Systolic Blood Pressure (mmHg) was assessed before drug administration and repeatedly after drug administration for the each session. Results are presented as the mean response over the entire session calculated as change from baseline.

Systolic Blood Pressure (mmHg) was assessed before drug administration and repeatedly after drug administration for the each session. Results are presented as the mean response over the entire session calculated as change from baseline.

Diastolic Blood Pressure (mmHg) was assessed before drug administration and repeatedly after drug administration for the each session. Results are presented as the mean response over the entire session calculated as change from baseline.

Diastolic Blood Pressure (mmHg) was assessed before drug administration and repeatedly after drug administration for the each session. Results are presented as the mean response over the entire session calculated as change from baseline.

Diastolic Blood Pressure (mmHg) was assessed before drug administration and repeatedly after drug administration for the each session. Results are presented as the mean response over the entire session calculated as change from baseline.

Participants complete the social choice task following administration of MDMA or placebo during which they choose between spending time 1) talking with another person; 2) sitting quietly alone; or 3) solving word problems. Choices were rated on a scale of 1 to 10 (with 10 indicating the highest level of desire to engage in that activity). The main outcome measure was desire to socialize (i.e., rating of "talking to another person").

Participants complete the social choice task following administration of MDMA or placebo during which they choose between spending time 1) talking with another person; 2) sitting quietly alone; or 3) solving word problems. Choices were rated on a scale of 1 to 10 (with 10 indicating the highest level of desire to engage in that activity). The main outcome measure was desire to socialize (i.e., rating of "talking to another person").

Participants complete the social choice task following administration of MDMA or placebo during which they choose between spending time 1) talking with another person; 2) sitting quietly alone; or 3) solving word problems. Choices were rated on a scale of 1 to 10 (with 10 indicating the highest level of desire to engage in that activity). The main outcome measure was desire to socialize (i.e., rating of "talking to another person").

Inclusion Criteria: 18-35, healthy, normal weight, high school education, normal electrocardiogram, no psychiatric disorders, occasional MDMA use Exclusion Criteria: current medications, night shift work, abnormal electrocardiogram, medical problems

http://druginfo.nlm.nih.gov/drugportal/ProxyServlet?mergeData=true&objectHandle=DBMaint&APPLICATION_NAME=drugportal&actionHandle=default&nextPage=jsp/drugportal/ResultScreen.jsp&TXTSUPERLISTID=0042542109&QV1=MDMA