This review (2016) compares MDMA with other stimulant drugs with regard to their social effects. The authors conclude that MDMA produces distinct effects in a variety of domains.

Abstract

“±3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that enhances sociability and feelings of closeness with others. These “prosocial” effects appear to motivate the recreational use of MDMA and may also form the basis of its potential as an adjunct to psychotherapy. However, the extent to which MDMA differs from prototypic stimulant drugs, such as dextroamphetamine, methamphetamine, and methylphenidate, in either its behavioral effects or mechanisms of action, is not fully known. The purpose of this review is to evaluate human laboratory findings of the social effects of MDMA compared to other stimulants, ranging from simple subjective ratings of sociability to more complex elements of social processing and behavior. We also review the neurochemical mechanisms by which these drugs may impact sociability. Together, the findings reviewed here lay the groundwork for better understanding the socially enhancing effects of MDMA that distinguish it from other stimulant drugs, especially as these effects relate to the reinforcing and potentially therapeutic effects of the drug.”

Authors: Anya K. Bershad, Melissa A. Miller, Matthew J. Baggott & Harriet de Wit

Summary

Introduction

Psychostimulant drugs produce feelings of euphoria and stimulation, increase confidence and enhance social interaction, and may be used as an adjunct to psychotherapy. MDMA is known for its unusual prosocial and “empathogenic” subjective effects, and may be used as a novel pharmacological class.

This review complements a recent paper on the psychosocial effects of MDMA, which concluded that MDMA has “prosocial” effects and dampens reactivity to negative emotional stimuli. It also examines the possible differences between MDMA and prototypic stimulant drugs, and how the mechanism of action may explain these effects.

MDMA is a popular recreational drug that enhances sociability and feelings of closeness with others. The extent to which MDMA differs from prototypic stimulant drugs in either its behavioral effects or mechanisms of action is not fully known.

Here, we review the effects of MDMA and other stimulants on self-report ratings, behavioral tasks, and social interactions in placebo-controlled, double-blind studies in human volunteers. We also discuss the potential neurochemical mechanisms of the observed prosocial effects.

Methods

Relevant articles were selected from PubMed and Google Scholar searches and reference lists of articles that included a sample of healthy human volunteers and assessed some aspect of socio-emotional function.

Self-report effects

MDMA and other psychostimulants increase feelings of sociability, euphoria, and positive mood, and these effects are based on self-reports of users. There are no corresponding naturalistic studies of social effects of other stimulants such as methamphetamine.

MDMA produces feelings of friendliness and sociability, and increases self-reports of feeling “social,” “stimulated,” “friendly”, and “talkative”, but also increases self-reports of feeling “closeness”, “trust”, and “openness” to others. These effects may be related to its effects on serotonin.

MDMA may increase feelings of social connectedness by dampening anxiety in social settings. However, there is mixed evidence that MDMA’s prosocial effects are secondary to a general anxiolytic effect, and MDMA may specifically dampen social anxiety versus other forms of anxiety.

MDMA increases feelings of authenticity, including self-regard and self-acceptance, which are associated with lessened defensiveness and feeling that one is able to be oneself. This finding is consistent with a recent naturalistic self-report study indicating that illicit ecstasy preparations increase self-compassion.

Social perception

Studies have investigated the acute effects of MDMA and other simulants on aspects of social perception, including the degree to which individuals respond to social and sexual visual stimuli and recognize emotions in the faces of others.

Responses to social images and empathy

Several studies have examined the effects of MDMA and other stimulants on ratings of positivity or negativity of images depicting social or nonsocial scenes. MDMA increased positive ratings of positive social images, but decreased positive ratings of positive images without social content.

MDMA and other stimulants have been shown to increase both explicit and implicit emotional empathy for positive situations, especially in men. However, methylphenidate did not increase emotional empathy for positive situations.

While there have been slight inconsistencies across studies, MDMA appears to increase emotional empathy, especially for positive situations. Although the drug use history of the participants may have little effect, it remains possible.

Studies have examined the effects of drugs on the cognitive component of empathy, which involves inferring the mental states of others. Facial expressions are potent social cues that signal how others are feeling. The findings from studies with MDMA are mixed, but tend to show that MDMA acts differentially on identification of positive and negative expressions. In contrast, d-amphetamine and methylphenidate enhanced the ability to identify both positive and negative expressions.

MDMA increases positive facial EMG responses to happy faces and attenuates amygdala activity during presentation of angry faces. The ventral striatum is activated during reward anticipation of both social and nonsocial reward. MDMA reduces social anxiety by dampening responses to negative emotional stimuli and increasing responses to positive stimuli, and these effects may be partly a result of the drug’s serotonergic activity.

MDMA and methylphenidate increase emotional responses to social stimuli, but not to sexual stimuli. This is consistent with user reports emphasizing increased emotional closeness and openness to sexual activity rather than sexual desire per se.

Social rejection

Responses to social cues can also be assessed using actual positive and negative social experiences. The computerized virtual ball-tossing game called Cyberball can be used to measure the effects of MDMA on perceptions of social rejection and acceptance. Frye et al. (2014) reported that MDMA reduced the effects of simulated social rejection on mood and self-esteem, and that the higher dose (1.5 mg/kg) also increased the estimated number of throws subjects received during the rejection condition.

Overall, these findings suggest that MDMA attenuates response to negative emotional stimuli and negative social experiences. This effect may help patients feel safer and more accepted in psychotherapy.

Speech

MDMA and other stimulants can alter many aspects of speech, including self-reports of feeling talkative, speech quantity, production, fluency, and content. However, MDMA does not affect speech production or verbal fluency, and may decrease synchronization between speakers.

Studies have investigated the effects of drugs on speech content, and have found that while both MDMA and prototypic stimulant drugs affect speech, their effects appear to be different, perhaps reflecting the different character of their social effects.

The evidence reviewed here suggests that stimulant drugs alter speech in ways that are consistent with their effects on social behaviors. MDMA appears to affect intimate social interaction and emotional openness.

Trust and reciprocity

MDMA (125 mg) increased prosocial behavior on the Social Value Orientation Task and increased ratings of trustworthiness of faces. Self-reported illicit ecstasy use was associated with more prosocial decisions on three cooperative behavior tasks. MDMA increased participants’ willingness to allocate money toward a friend (but not a stranger) in a Welfare Trade-Off Task, and this effect coincides with a report that the neuropeptide oxytocin selectively enhances trust among individual members of a social in-group.

Social interactions

In-person social interaction is another behavioral process that has been used to investigate the pro-social effects of drugs. MDMA can enhance social experiences and, in turn, the presence of others may heighten the rewarding effects of the drug.

MDMA increased perceptions of empathy from others in one study, which is distinguishable from reports that the drug increased empathy for others. This effect is consistent with reports that MDMA increased comfort when describing autobiographical memories to a researcher.

Kirkpatrick et al. (2015) examined the effects of MDMA in participants who were tested under social conditions, with another person, or isolated conditions. They found that participants who received MDMA in the presence of another participant showed the greatest increases in physiological responses to the drug. Two studies have investigated the effects of social settings on responses to d-amphetamine. One study found that subjects had greater physiological responses when tested with other participants compared with alone, but not subjective effects.

Mechanisms

MDMA preferentially increases serotonin and norepinephrine release and indirectly induces dopamine release as a consequence of serotonergic release, and directly inhibits dopamine reuptake. It also induces acetylcholine release and has low micromolar affinity for histamine H1 and muscarinic M1 and M2 receptors.

MDMA’s complex pharmacology makes it difficult to determine the exact mechanisms by which it produces its unusual prosocial effects. However, studies with humans indicate that both serotonergic and noradrenergic mechanisms are likely important.

MDMA elevates oxytocin levels in the blood and may be a contributing factor to the social effects of MDMA. However, methamphetamine does not appear to induce oxytocin release, lending weight to the possibility that different oxytocinergic effects may contribute to differential social effects of MDMA and prototypic stimulants.

MDMA may also stimulate vasopressin release, which may contribute to the prosocial effects of the drug. However, V1A vasopressin receptor antagonism with SR49059 only partially blocked the prosocial effects of MDMA in rodents.

The 5-HT1A antagonist pindolol had little effect on responses to MDMA in humans, and SSRIs attenuated self-reported effects of MDMA, but it is unclear to what extent non-serotonergic mechanisms contribute to self-reported social effects of MDMA.

MDMA affects both serotonin and norepinephrine, and both are involved in the social effects of MDMA. Reboxetine reduces only norepinephrine, but not serotonin, or the other social visual analog items.

Conclusions and further directions

MDMA has distinct effects that are distinguishable from prototypic stimulants across several social domains, including appraisal of social stimuli and naturalistic social interactions. However, relatively few studies have directly compared MDMA to other stimulants, and thus the full constellation of social effects remains to be determined.

Most studies included in this review are highly controlled laboratory-based investigations into emotion processing. Self-report ratings provide a critical index of the psychological effects of MDMA and prototypic stimulants, but these measures have their own limitations.

MDMA may strengthen the patient-therapist relationship, alter processing of external and internally generated emotional stimuli, and affect memory. It has been suggested that psychotherapy can be viewed as the activation of negative emotional memories within a positively valenced therapeutic context.