OPEN Foundation

H. de Wit

The Ups and Downs of 3,4-Methylenedioxymethamphetamine: Linking Subjective Effects to Spontaneous Brain Function

October 15, 2015 / MDMA, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , ,

Abstract

Psychoactive drugs, especially drugs with so-called psychedelic properties, exert profound effects on sensory perception, cognition, and emotion by modulating target neurotransmitter systems. The compound 3,4-methylenedioxymethamphetamine (MDMA) exerts stimulant and psychedelic effects through its actions on dopamine, norepinephrine, and serotonin (5-hydroxytryptamine, [5-HT]) transporters, by inhibiting their reuptake and stimulating their release. In addition to producing euphoria and positive mood, MDMA appears to produce unique “prosocial” or “empathogenic” feelings.

de Wit, H., Gorka, S. M., & Phan, K. L. (2015). The Ups and Downs of 3, 4-Methylenedioxymethamphetamine: Linking Subjective Effects to Spontaneous Brain Function. Biological psychiatry, 78(8), 519-521. http://dx.doi.org/10.1016/j.biopsych.2015.08.015
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Intimate insight: MDMA changes how people talk about significant others

April 28, 2015 / MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

Rationale: ±3,4-methylenedioxymethamphetamine (MDMA) is widely believed to increase sociability. The drug alters speech production and fluency, and may influence speech content. Here, we investigated the effect of MDMA on speech content, which may reveal how this drug affects social interactions.

Method: Thirty-five healthy volunteers with prior MDMA experience completed this two-session, within-subjects, double-blind study during which they received 1.5 mg/kg oral MDMA and placebo. Participants completed a five-minute standardized talking task during which they discussed a close personal relationship (e.g. a friend or family member) with a research assistant. The conversations were analyzed for selected content categories (e.g. words pertaining to affect, social interaction, and cognition), using both a standard dictionary method (Pennebaker’s Linguistic Inquiry and Word Count: LIWC) and a machine learning method using random forest classifiers.

Results: Both analytic methods revealed that MDMA altered speech content relative to placebo. Using LIWC scores, the drug increased use of social and sexual words, consistent with reports that MDMA increases willingness to disclose. Using the machine learning algorithm, we found that MDMA increased use of social words and words relating to both positive and negative emotions.

Conclusions: These findings are consistent with reports that MDMA acutely alters speech content, specifically increasing emotional and social content during a brief semistructured dyadic interaction. Studying effects of psychoactive drugs on speech content may offer new insights into drug effects on mental states, and on emotional and psychosocial interaction.

Baggott, M. J., Kirkpatrick, M. G., Bedi, G., & de Wit, H. (2015). Intimate insight: MDMA changes how people talk about significant others. Journal of Psychopharmacology, 0269881115581962. https://dx.doi.org/10.1177/0269881115581962
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Prosocial effects of MDMA: A measure of generosity

March 3, 2015 / MDMA, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , , ,

Abstract

Background: 3,4-methylenedioxymethamphetamine (MDMA) produces “prosocial” effects that contribute to its recreational use. Few studies have examined the cognitive and behavioral mechanisms by which MDMA produces these effects. Here we examined the effect of MDMA on a specific prosocial effect, i.e. generosity, using a task in which participants make decisions about whether they or another person will receive money (Welfare Trade-Off Task; WTT).

Methods: The project included one study without drug administration and one with MDMA. In Study 1, we administered the WTT to healthy adults (N = 361) and examined their performance in relation to measures of personality and socioeconomic status. In Study 2, healthy volunteers with MDMA experience (N = 32) completed the WTT after MDMA administration (0, 0.5, or 1.0 mg/kg).

Results: As expected, in both studies participants were more generous with a close friend than an acquaintance or stranger. In Study 1, WTT generosity was related to household income and trait Agreeableness. In Study 2, MDMA (1.0 mg/kg) increased generosity toward a friend but not a stranger, whereas MDMA (0.5 mg/kg) slightly increased generosity toward a stranger, especially among female participants.

Conclusions: These data indicate that the WTT is a valuable, novel tool to assess a component of prosocial behavior, i.e. generosity to others. The findings support growing evidence that MDMA produces prosocial effects, but, as with oxytocin, these appear to depend on the social proximity of the relationships. The brain mechanisms underlying the construct of generosity, or the effects of MDMA on this measure, remain to be determined.

Kirkpatrick, M., Delton, A. W., de Wit, H., & Robertson, T. E. (2015). Prosocial effects of MDMA: A measure of generosity. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881115573806
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A window into the intoxicated mind? Speech as an index of psychoactive drug effects.

April 3, 2014 / MDMA, Other subjects, Other substances, Papers, Personality, Psychiatry, Psychology, Publications / By / , , , , ,

Abstract

Abused drugs can profoundly alter mental states in ways that may motivate drug use. These effects are usually assessed with self-report, an approach that is vulnerable to biases. Analyzing speech during intoxication may present a more direct, objective measure, offering a unique ‘window’ into the mind. Here, we employed computational analyses of speech semantic and topological structure after ±3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) and methamphetamine in 13 ecstasy users. In 4 sessions, participants completed a 10-min speech task after MDMA (0.75 and 1.5 mg/kg), methamphetamine (20 mg), or placebo. Latent Semantic Analyses identified the semantic proximity between speech content and concepts relevant to drug effects. Graph-based analyses identified topological speech characteristics. Group-level drug effects on semantic distances and topology were assessed. Machine-learning analyses (with leave-one-out cross-validation) assessed whether speech characteristics could predict drug condition in the individual subject. Speech after MDMA (1.5 mg/kg) had greater semantic proximity than placebo to the concepts friend, support, intimacy, and rapport. Speech on MDMA (0.75 mg/kg) had greater proximity to empathy than placebo. Conversely, speech on methamphetamine was further from compassion than placebo. Classifiers discriminated between MDMA (1.5 mg/kg) and placebo with 88% accuracy, and MDMA (1.5 mg/kg) and methamphetamine with 84% accuracy. For the two MDMA doses, the classifier performed at chance. These data suggest that automated semantic speech analyses can capture subtle alterations in mental state, accurately discriminating between drugs. The findings also illustrate the potential for automated speech-based approaches to characterize clinically relevant alterations to mental state, including those occurring in psychiatric illness.

Bedi, G., Cecchi, G. A., Slezak, D. F., Carrillo, F., Sigman, M., & de Wit, H. (2014). A window into the intoxicated mind? speech as an index of psychoactive drug effects. Neuropsychopharmacology. https://dx.doi.org/10.1038/npp.2014.80

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MDMA decreases the effects of simulated social rejection

February 8, 2014 / Anxiety disorders / PTSD, MDMA, Papers, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , ,

Abstract

3-4-Methylenedioxymethamphetamine (MDMA) increases self-reported positive social feelings and decreases the ability to detect social threat in faces, but its effects on experiences of social acceptance and rejection have not been determined. We examined how an acute dose of MDMA affects subjective and autonomic responses to simulated social acceptance and rejection. We predicted that MDMA would decrease subjective responses to rejection. On an exploratory basis, we also examined the effect of MDMA on respiratory sinus arrhythmia (RSA), a measure of parasympathetic cardiac control often thought to index social engagement and emotional regulation. Over three sessions, healthy adult volunteers with previous MDMA experience (N = 36) received capsules containing placebo, 0.75 or 1.5 mg/kg of MDMA under counter-balanced double-blind conditions. During expected peak drug effect, participants played two rounds of a virtual social simulation task called “Cyberball” during which they experienced acceptance in one round and rejection in the other. During the task we also obtained electrocardiograms (ECGs), from which we calculated RSA. After each round, participants answered questionnaires about their mood and self-esteem. As predicted, MDMA decreased the effect of simulated social rejection on self-reported mood and self-esteem and decreased perceived intensity of rejection, measured as the percent of ball tosses participants reported receiving. Consistent with its sympathomimetic properties, MDMA decreased RSA as compared to placebo. Our finding that MDMA decreases perceptions of rejection in simulated social situations extends previous results indicating that MDMA reduces perception of social threat in faces. Together these findings suggest a cognitive mechanism by which MDMA might produce pro-social behavior and feelings and how the drug might function as an adjunct to psychotherapy. These phenomena merit further study in non-simulated social environments.

Frye, C. G., Wardle, M. C., Norman, G. J., & de Wit, H. (2014). MDMA decreases the effects of simulated social rejection. Pharmacology Biochemistry and Behavior, 117, 1-6. https://dx.doi.org/10.1016/j.pbb.2013.11.030

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Is Ecstasy an “Empathogen”? Effects of ±3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others

December 15, 2010 / MDMA, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , ,

Abstract

Background: Users of MDMA (“ecstasy”) report that the drug produces unusual psychological effects, including increased empathy and prosocial feelings. These “empathogenic” effects are cited as reasons for recreational ecstasy use and also form the basis for the proposed use of MDMA in psychotherapy. However, they have yet to be characterized in controlled studies. Here, we investigate effects of MDMA on an important social cognitive capacity, the identification of emotional expression in others, and on socially relevant mood states.

Methods: Over four sessions, healthy ecstasy-using volunteers (n = 21) received MDMA (.75, 1.5 mg/kg), methamphetamine (METH) (20 mg), and placebo under double-blind, randomized conditions. They completed self-report ratings of relevant affective states and undertook tasks in which they identified emotions from images of faces, pictures of eyes, and vocal cues.

Results: MDMA (1.5 mg/kg) significantly increased ratings of feeling “loving” and “friendly”, and MDMA (.75 mg/kg) increased “loneliness”. Both MDMA (1.5 mg/kg) and METH increased “playfulness”; only METH increased “sociability”. MDMA (1.5 mg/kg) robustly decreased accuracy of facial fear recognition relative to placebo.

Conclusion: The drug MDMA increased “empathogenic” feelings but reduced accurate identification of threat-related facial emotional signals in others, findings consistent with increased social approach behavior rather than empathy. This effect of MDMA on social cognition has implications for both recreational and therapeutic use. In recreational users, acute drug effects might alter social risk-taking while intoxicated. Socioemotional processing alterations such as those documented here might underlie possible psychotherapeutic benefits of this drug; further investigation of such mechanisms could inform treatment design to maximize active components of MDMA-assisted psychotherapy.

Bedia, G., Hymana, D., & de Wit, H. (2010). Is Ecstasy an “Empathogen”? Effects of ±3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others. Biological Psychiatry, 68(12), 1134-1140. http://dx.doi.org/10.1016/j.biopsych.2010.08.003
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30 April - Q&A with Rick Strassman

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