Effects of MDMA on attention to positive social cues and pleasantness of affective touch

This randomized, double-blind, placebo-controlled study (n=36) investigated the effects of MDMA (52.5 to 105 mg/70kg) and methamphetamine (20 mg) in healthy young adults on behavioral and psychophysiological response to socially relevant, “affective” touch, and visual attention to emotional faces. The tests showed that MDMA positively influenced responses to affective touch, but neither drug influenced ratings of observed touch.

Abstract

“The psychostimulant drug ±3,4-methylenedioxymethamphetamine (MDMA) reportedly produces distinctive feelings of empathy and closeness with others. MDMA increases social behavior in animal models and has shown promise in psychiatric disorders, such as autism spectrum disorder (ASD) and post-traumatic stress disorder (PTSD). How it produces these prosocial effects is not known. This behavioral and psychophysiological study examined the effects of MDMA, compared with the prototypical stimulant methamphetamine (MA), on two measures of social behavior in healthy young adults: (i) responses to socially relevant, “affective” touch, and (ii) visual attention to emotional faces. Men and women (N = 36) attended four sessions in which they received MDMA (0.75 or 1.5 mg/kg), MA (20 mg), or a placebo in randomized order under double-blind conditions. Responses to experienced and observed affective touch (i.e., being touched or watching others being touched) were assessed using facial electromyography (EMG), a proxy of affective state. Responses to emotional faces were assessed using electrooculography (EOG) in a measure of attentional bias. Subjective ratings were also included. We hypothesized that MDMA, but not MA, would enhance the ratings of pleasantness and psychophysiological responses to affective touch and increase attentional bias toward positive facial expressions. Consistent with this, we found that MDMA, but not MA, selectively enhanced ratings of pleasantness of experienced affective touch. Neither drug altered the ratings of pleasantness of observed touch. On the EOG measure of attentional bias, MDMA, but not MA, increased attention toward happy faces. These results provide new evidence that MDMA can enhance the experience of positive social interactions; in this case, pleasantness of physical touch and attentional bias toward positive facial expressions. The findings are consistent with evidence that the prosocial effects are unique to MDMA relative to another stimulant. Understanding the behavioral and neurobiological processes underlying the distinctive social effects of MDMA is a key step to developing the drug for psychiatric disorders.”

Authors: Anya K. Bershad, Leah M. Mayo, Kathryne Van Hedger, Francis McGlone, Susannah C. Walker & Harriet de Wit

Summary

INTRODUCTION

The psychostimulant drug MDMA has been labeled an “empathogen – entactogen” and increases feelings of empathy and interpersonal closeness in both rodents and healthy human volunteers. Its effects are distinct from the effects of other pharmacologically related psychostimulants.

The sense of touch is central to social communication, and affective touch is believed to be mediated by activation of C-tactile (CT) afferents, located on non-glabrous (hairy) skin. CT-firing mediated affective touch influences both the self-reported hedonic experience as well as the implicit facial muscle activity indicative of a positive affective response.

The positive hedonic qualities of affective touch may be due to unique neural and molecular underpinnings, including increased levels of serotonin and oxytocin, both of which are influenced by MDMA.

We measured how people responded to receiving and observing CT-optimal and non-optimal touch, and hypothesized that MDMA, but not MA, would increase perceived pleasantness of touch at the CT-optimal velocity.

We assessed the effects of the drug on participants’ attention to positive versus negative social cues by recording eye movements in a dot-probe task. We found that the drug increased attention bias toward positive expressions but decreased attention bias toward negative expressions. MDMA produces prosocial effects by altering oxytocinergic signaling, and this study was conducted with healthy adult volunteers to examine how MDMA produces prosocial effects.

Young adults received placebo, 0.75 mg/kg MDMA, 1.5 mg/kg MDMA, or 20 mg of methamphetamine during four 4-h laboratory sessions.

We recruited 36 healthy volunteers aged 18-40 who reported having used MDMA between 4 and 40 times in their lifetime. They underwent a physical and psychiatric screening, including an in-person psychiatric interview and a detailed drug use history questionnaire.

During an orientation session, participants were provided with information about the study and gave informed consent. They were told they could receive a stimulant, sedative, cannabinoid, or placebo.

Participants completed four 4.5-h sessions in a research laboratory. They were allowed to watch movies, read, or relax during the sessions, and were tested for drugs and alcohol before each session. Participants completed baseline measures for their mood and cardiovascular state, took a capsule containing MA (20 mg), MDMA (0.75 or 1.5 mg/kg), or placebo, relaxed for 1 h, and completed the attention bias task, the observed touch task, and experienced touch task.

Subjective questionnaires assess subjective drug effects and include questions on whether the subject liked or disliked the drug effect.

In this task, participants were touched with a 5-cm-wide goat hair brush. They rated the pleasantness of the touch using a 7-point Likert scale, and were given a 1 – 2 s variable inter-trial interval between ratings.

Participants viewed 6-s videos depicting a left arm, back, or palm resting on a white background, being stroked by a hand at a rate of 0 (static), 3 or 30 cm/s. Facial muscle activity was assessed via facial EMG, and a pleasantness rating followed each video.

EMG was recorded from the corrugator and zygomatic muscles and used to determine emotional reactivity to touch tasks. The signals were amplified, filtered, digitized, re-filtered, rectified, and integrated over 20 ms.

The Attention Bias Task (ABT) consisted of showing participants pairs of faces, one on each side of the screen, and asking them to indicate whether a probe presented following the 2-s display of the face pair was a square or a circle. EOG data were collected with 4-mm Ag/AgCl electrodes attached 1.5 cm from the outer canthus of each eye and analyzed by trained, blinded scorers.

Statistical analysis was conducted using SPSS. MDMA and MA were compared using linear contrasts, and touch task data was analyzed using repeated measures ANOVAs, with dose and touch velocity as within-subject factors.

RESULTS

Subjective drug effects increased with increasing doses of MDMA and MA. The higher dose of MDMA increased ratings of “dislike drug” and “want more” while all doses increased ratings of “feel high”.

The higher dose of MDMA and MA significantly increased ratings of “anxious”, “insightful” and “stimulated”, as well as “sociable” and “lonely”. The 1.5 mg/kg dose of MDMA tended to increase ratings of “playful” and “loving”, but not of confident, friendly, or dizzy.

MA and both doses of MDMA significantly increased MAP and heart rate in rats.

Self-report ratings of pleasantness differed across two velocities, with slow touch being rated as more pleasant than non-optimal touch. Both doses of MDMA increased self-reported ratings of pleasantness for slow touch.

MDMA had a linear dose effect on zygomatic responses at both velocities, but no significant drug velocity interaction was observed.

Fast touch elicited greater muscle activity than slow touch, but the drug/dose had no significant effect on this measure.

There was no significant difference in ratings of static and fast touch, and there was no significant main effect of drug/dose or drug/dose velocity interaction.

No significant effects of velocity or drug were found on zygomatic reactivity, though MDMA increased zygomatic activity.

MDMA increased the number of times participants looked toward happy faces before neutral faces, but did not affect gazes toward other emotion types. MA increased the first gaze toward angry faces, but MDMA did not.

During the placebo session, 23 participants correctly guessed what they had received, while the others guessed that they had taken valium, MDMA, MA, or marijuana. During the MDMA session, 17 participants correctly guessed what they had received, while the others guessed that they had taken valium, MDMA, MA, or placebo.

DISCUSSION

In this study, MDMA increased pleasantness ratings of affective touch at the CT-optimal frequency, without significantly affecting pleasantness of non-optimal touch, and tended to increase zygomatic reactivity to touch at both frequencies, but did not significantly affect corrugator activity.

We examined affective responses to soft touch, using subjective ratings and psychophysical indices. Our results suggest that MDMA enhances pleasantness ratings of affective touch, which is consistent with previous evidence that MDMA may act directly upon the neural circuits involved in responding to affective touch.

In our study, MDMA increased zygomatic reactivity to both velocities of touch, and this increase was correlated with pleasantness ratings. This suggests that MDMA enhances positive psychophysiological responses to both CT-optimal and non-optimal touch.

MDMA alters responses to affective touch by altering serotonergic and oxytocinergic signaling. MDMA increases plasma oxytocin levels, and some studies have found that oxytocin levels are correlated with the prosocial effects of MDMA.

The increase in oxytocin levels observed after the administration of MDMA may be secondary to the drug’s effects on the serotonergic system. Pretreatment with a selective serotonin reuptake inhibitor (SSRI) attenuates some subjective effects of MDMA, but not the social effects.

MDMA may have some subjective effects that are caused by the serotonergic system, noradrenergic system, and dopaminergic system. The effects may be inhibited by certain drugs.

MDMA has been shown to enhance the pleasantness of social touch in patients with PTSD and autism spectrum disorder, and may help normalize affective responses to touch in these populations.

MDMA enhanced attention bias toward happy faces, as measured by eye movements, and may underlie its effectiveness in a therapeutic context.

Our study had a number of strengths, including double-blind conditions, a standardized and sensitive indicator of psychoactive drug effects, and the use of two doses of MDMA and a comparison drug to demonstrate the pharmacological profile of the drug.

This study tested the effects of MDMA on responses to affective touch applied to non-glabrous skin areas. It is not known if individuals with psychiatric symptoms would respond similarly to the drug, and the study was conducted in a highly controlled laboratory environment.

This study examined the effects of MDMA on responses to affective touch, and compared these effects with another prototypical psychostimulant, MA. MDMA enhanced the pleasantness of CT-optimal touch, and biased visual attention to positive emotional faces.