OPEN Foundation

J. Coyle

Effects of the Psychedelic Amphetamine MDA (3,4-Methylenedioxyamphetamine) in Healthy Volunteers.

April 9, 2019 / MDMA, Other substances, Papers, Psychology, Psychopharmacology, Publications, Safety / By / , , , , , ,

Abstract

Entactogens such as 3,4-Methylenedioxymethamphetamine (MDMA, “molly”, “ecstasy”) appear to have unusual, potentially therapeutic, emotional effects. Understanding their mechanisms can benefit from clinical experiments with related drugs. Yet the first known drug with such properties, 3,4-Methylenedioxyamphetamine (MDA), remains poorly studied and its pharmacokinetics in humans are unknown. We conducted a within-subjects, double-blind, placebo-controlled study of 1.4 mg/kg oral racemic MDA and compared results to those from our prior similar studies with 1.5 mg/kg oral racemic MDMA. MDA was well-tolerated by participants. MDA induced robust increases in heart rate and blood pressure and increased cortisol and prolactin to a similar degree as MDMA. MDA self-report effects shared features with MDMA as well as with classical psychedelics. MDA self-report effects lasted longer than those of MDMA, with MDA effects remaining elevated at 8 h while MDMA effects resolved by 6 h. Cmax and AUC0-∞ for MDA were 229 ± 39 (mean ± SD) and 3636 ± 958 µg/L for MDA and 92 ± 61 and 1544 ± 741 µg/L for the metabolite 4-hydroxy-3-methoxyamphetamine (HMA). There was considerable between-subject variation in MDA/HMA ratios. The similarity of MDA and MDMA pharmacokinetics suggests that the greater duration of MDA effects is due to pharmacodynamics rather than pharmacokinetics.
Baggott, M. J., Garrison, K. J., Coyle, J. R., Galloway, G. P., Barnes, A. J., Huestis, M. A., & Mendelson, J. E. (2019). Effects of the psychedelic amphetamine MDA (3, 4-methylenedioxyamphetamine) in healthy volunteers. Journal of psychoactive drugs, 1-10., https://doi.org/10.1080/02791072.2019.1593560
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Effects of 3,4-methylenedioxymethamphetamine on socioemotional feelings, authenticity, and autobiographical disclosure in healthy volunteers in a controlled setting

February 15, 2016 / MDMA, Papers, Personality, Psychiatry, Psychology, Psychotherapy, Publications / By / , , , , ,

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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Quantitative Analysis of Narrative Reports of Psychedelic Drugs

June 1, 2012 / Ayahuasca, Cacti / Mescaline, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Other disciplines, Other subjects, Other substances, Papers, Publications, Salvia / Salvinorin A / By / , ,

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

December 8, 2010 / Other subjects, Papers, Psychopharmacology, Publications, Salvia / Salvinorin A / By / , , , , , ,

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

December 2, 2010 / Other subjects, Other substances, Papers, Psychology, Publications / By / , , , , ,

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

September 21, 2010 / HPPD, LSD, Neuroscience, Other disciplines, Other subjects, Other substances, Papers, Publications / By / , , , ,

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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30 April - Q&A with Rick Strassman

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