OPEN Foundation

M. Baggott

The effects of MDMA on socio-emotional processing: Does MDMA differ from other stimulants?

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.

Bershad, A. K., Miller, M. A., Baggott, M. J., & de Wit, H. (2016). The effects of MDMA on socio-emotional processing: Does MDMA differ from other stimulants?. Journal of Psychopharmacology, 0269881116663120.
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Effects of 3,4-methylenedioxymethamphetamine on socioemotional feelings, authenticity, and autobiographical disclosure in healthy volunteers in a controlled setting

Abstract

The drug 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”, “molly”) is a widely used illicit drug and experimental adjunct to psychotherapy. MDMA has unusual, poorly understood socioemotional effects, including feelings of interpersonal closeness and sociability. To better understand these effects, we conducted a small (n=12) within-subjects double-blind placebo controlled study of the effects of 1.5 mg/kg oral MDMA on social emotions and autobiographical disclosure in a controlled setting. MDMA displayed both sedative- and stimulant-like effects, including increased self-report anxiety. At the same time, MDMA positively altered evaluation of the self (i.e. increasing feelings of authenticity) while decreasing concerns about negative evaluation by others (i.e. decreasing social anxiety). Consistent with these feelings, MDMA increased how comfortable participants felt describing emotional memories. Overall, MDMA produced a prosocial syndrome that seemed to facilitate emotional disclosure and that appears consistent with the suggestion that it represents a novel pharmacological class.

Baggott, M. J., Coyle, J. R., Siegrist, J. D., Garrison, K. J., Galloway, G. P., & Mendelson, J. E. (2016). Effects of 3, 4-methylenedioxymethamphetamine on socioemotional feelings, authenticity, and autobiographical disclosure in healthy volunteers in a controlled setting. Journal of psychopharmacology (Oxford, England). dx.doi.org/10.1177/0269881115626348

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Psychedelics and creativity: a review of the quantitative literature

Abstract

After a 40-year hiatus, the question of whether psychedelics can increase creativity is being asked with renewed vigor. This article critically reviews the conceptual issues of studying psychedelic-induced creativity by summarizing the limited evidence on the question and suggesting two broader frameworks. There are two important challenges to researchers on this topic. One is to separate creativity from other effects of the drug that may be mistaken for creativity. The second is to develop operational measures to quantify it. This article reviews the major studies assessing creativity (or related constructs) induced by psychedelics, including a reanalysis of raw data from one study. Results are modest and inconclusive but are consistent with reports that psychedelics give rise to unusual or novel thoughts. Given the lack of robust changes in creativity measures, I suggest creativity may be too specific of a construct to accurately and fully characterize the putatively beneficial cognitive changes that psychedelic users report. Feelings of creativity may be an inconsistent result of a more general effect of these drugs, such as alterations in availability of mental representations or changes in Bayesian inference. Ultimately, creativity may not be a sufficiently creative construct to capture the beneficial effects of psychedelics.

Baggott, M. J. (2015). Psychedelics and creativity: a review of the quantitative literature. PeerJ PrePrints, 3, e1468. https://dx.doi.org/10.7287/peerj.preprints.1202v1
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Intimate insight: MDMA changes how people talk about significant others

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/
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A brief survey of drug use and other activities preceding mystical-religious experiences

Abstract

Many people report having had mystical-religious experiences. The prevalence of these experiences has increased over time, which suggests changing cultural factors may contribute the experience. I conducted an online survey of 6,209 adults to determine how common different activities, including drug use, were before the onset of a mystical-religious experience. 19.6% (1,045) reported having had a mystical-religious experience and were asked a follow-up question on their activities before the experience. The most commonly endorsed pre-onset activity categories were: Prayer, meditation, or contemplation (37.2%); Being outdoors in nature (19.6%); and Religious ceremony, practice, or ritual (16.1%). Less commonly, respondents reported fasting (5.7%) or drug use (4.7%). A large percent (35.2%) reported not engaging in any of these activities before their experiences. Psychoactive drugs and nature are precedents to mystical-religious experience that are not selectively associated with traditional religious institutions and deserve additional study.

Baggott MJ. (2015) A brief survey of drug use and other activities preceding mystical-religious experiences Available at: https://github.com/mattbaggott/mysticalsurvey/blob/master/results/Baggott%20mystical%20survey%20March2015.pdf.
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Quantitative Analysis of Narrative Reports of Psychedelic Drugs

Abstract

Background

Psychedelic drugs facilitate profound changes in consciousness and have potential to provide insights into the nature of human mental processes and their relation to brain physiology. Yet published scientific literature reflects a very limited understanding of the effects of these drugs, especially for newer synthetic compounds. The number of clinical trials and range of drugs formally studied is dwarfed by the number of written descriptions of the many drugs taken by people. Analysis of these descriptions using machine-learning techniques can provide a framework for learning about these drug use experiences.

Methods

We collected 1000 reports of 10 drugs from the drug information website Erowid.org and formed a term-document frequency matrix. Using variable selection and a random-forest classifier, we identified a subset of words that differentiated between drugs.

Results

A random forest using a subset of 110 predictor variables classified with accuracy comparable to a random forest using the full set of 3934 predictors. Our estimated accuracy was 51.1%, which compares favorably to the 10% expected from chance. Reports of MDMA had the highest accuracy at 86.9%; those describing DPT had the lowest at 20.1%. Hierarchical clustering suggested similarities between certain drugs, such as DMT and Salvia divinorum.

Conclusion

Machine-learning techniques can reveal consistencies in descriptions of drug use experiences that vary by drug class. This may be useful for developing hypotheses about the pharmacology and toxicity of new and poorly characterized drugs.

Coyle, J. R., Presti, D. E., Baggott, M. J. (2012). Quantitative Analysis of Narrative Reports of Psychedelic Drugs.
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Lack of effect of sublingual salvinorin A, a naturally occurring kappa opioid, in humans: a placebo-controlled trial

Abstract

Rationale: Salvinorin A (SA) is a highly selective kappa opioid receptor agonist and the putative psychoactive compound in Salvia divinorum (SD), an increasingly abused hallucinogenic plant.

Objectives: The objectives of this study were to characterize the physiological and subjective effects of SA versus placebo and measure drug and metabolite levels.

Methods: Sublingual SA doses up to 4 mg were administered in dimethyl sulfoxide/polyethylene glycol 400 solution to eight SD-experienced subjects using a placebo-controlled ascending-dose design.

Results: No dose of SA produced significantly greater physiological or subjective effects than placebo. Furthermore, effects did not resemble reported “typical” effects of smoked SD. SA was detectable in plasma and urine, but was, in most cases, below the reliable limit of quantification (0.5 ng/mL).

Cconclusions: Our results suggest that the sublingual bioavailability of SA is low. Higher doses, alternate formulations, or alternate routes of administration will be necessary to study the effects of SA in humans.

Mendelson, J. E., Coyle, J. R., Lopez, J.C., Baggott, M. J., Flower, K., Everhart, E. T., … Cohen, B. M. (2010). Lack of effect of sublingual salvinorin A, a naturally occurring kappa opioid, in humans: a placebo-controlled trial. Psychopharmacology, 214(4), 933-939. http://dx.doi.org/10.1007/s00213-010-2103-5
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Investigating the Mechanisms of Hallucinogen-Induced Visions Using 3,4-Methylenedioxyamphetamine (MDA): A Randomized Controlled Trial in Humans

Abstract

Background: The mechanisms of drug-induced visions are poorly understood. Very few serotonergic hallucinogens have been studied in humans in decades, despite widespread use of these drugs and potential relevance of their mechanisms to hallucinations occurring in psychiatric and neurological disorders.

Methodology/Principal Findings: We investigated the mechanisms of hallucinogen-induced visions by measuring the visual and perceptual effects of the hallucinogenic serotonin 5-HT2AR receptor agonist and monoamine releaser, 3,4-methylenedioxyamphetamine (MDA), in a double-blind placebo-controlled study. We found that MDA increased self-report measures of mystical-type experience and other hallucinogen-like effects, including reported visual alterations. MDA produced a significant increase in closed-eye visions (CEVs), with considerable individual variation. Magnitude of CEVs after MDA was associated with lower performance on measures of contour integration and object recognition.

Conclusions/Significance: Drug-induced visions may have greater intensity in people with poor sensory or perceptual processing, suggesting common mechanisms with other hallucinatory syndromes. MDA is a potential tool to investigate mystical experiences and visual perception.

Baggott, M. J., Siegrist, J. D., Galloway, G. P., Robertson, L. C., Coyle, J. R., & Mendelson, J. E. (2010). Investigating the Mechanisms of Hallucinogen-Induced Visions Using 3,4-Methylenedioxyamphetamine (MDA): A Randomized Controlled Trial in Humans. PLoS ONE, 5(12), 1-13. http://dx.doi.org/10.1371/journal.pone.0014074
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Abnormal visual experiences in individuals with histories of hallucinogen use: A web-based questionnaire

Abstract

Despite longstanding reports of prolonged or reoccurring perceptual changes in a subset of hallucinogen users, very little is known about Hallucinogen Persisting Perception Disorder and related visual abnormalities in hallucinogen users. We used an online questionnaire to document the symptoms and relationship to drug use of unusual visual phenomena in hallucinogen users. 16,192 individuals viewed the information sheet and 2679 were included in the study. Of these, 224 reported having unrelated diagnoses associated with unusual visual experiences and were excluded from main analyses. Most (60.6%) of the remaining 2455 participants reported having experienced drug-free visual experiences that resembled hallucinogen effects. Probability of experiencing constant or near-constant symptoms was predicted by greater past exposure to specific hallucinogens, including lysergic acid diethylamide (LSD). Although symptoms were common, few (104, or 4.2% of the sample) found them distressing or impairing enough to consider seeking treatment. Visual changes in hallucinogen users may be more common than previously suspected and are worthy of further study.

Baggott, M. J., Coyle, J. R., Erowid, E., Erowid, F., & Robertson, L. C. (2011). Abnormal visual experiences in individuals with histories of hallucinogen use: A web-based questionnaire. Drug and alcohol dependence, 114(1), 61-67. http://dx.doi.org/10.1016/j.drugalcdep.2010.09.006
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