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MDMA

The History of MDMA as an Underground Drug in the United States, 1960-1979

March 3, 2016 / History, MDMA, New substances, Papers, Publications / By / ,

Abstract

MDMA (3,4-methylenedioxy-methylamphetamine, a.k.a. “ecstasy”) was first synthesized in 1912 and resynthesized more than once for pharmaceutical reasons before it became a popular recreational drug. Partially based on previously overlooked U.S. government documentation, this article reconstructs the early history of MDMA as a recreational drug in the U.S. from 1960 to 1979. According to the literature, MDMA was introduced as a street drug at the end of the 1960s. The first forensic detection of MDMA “on the street” was reported in 1970 in Chicago. It appears that MDMA was first synthesized by underground chemists in search of “legal alternatives” for the closely related and highly sought-after drug MDA, which was scheduled under the Controlled Substances Act (CSA) in 1970. Until 1974, nearly all MDMA street samples seized came from the U.S. Midwest, the first “hot region” of MDMA use. In Canada, MDMA was first detected in 1974 and scheduled in 1976. From 1975 to 1979, MDMA was found in street samples in more than 10 U.S. states, the West Coast becoming the major “hot region” of MDMA use. Recreational use of MDMA spread across the U.S. in the early 1980s, and in 1985 it was scheduled under the CSA.

Passie, T., & Benzenhöfer, U. (2016). The history of MDMA as an underground drug in the United States, 1960–1979. Journal of psychoactive drugs, 48(2), 67-75., 10.1080/02791072.2015.1128580

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Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective

February 23, 2016 / MDMA, Other subjects, Papers, Psychiatry, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND:

Ecstasy use has been associated with short-term and long-term memory deficits on a standard Word Learning Task (WLT). The clinical relevance of this has been debated and is currently unknown. The present study aimed at evaluating the clinical relevance of verbal memory impairment in Ecstasy users. To that end, clinical memory impairment was defined as decrement in memory performance that exceeded the cut-off value of 1.5 times the standard deviation of the average score in the healthy control sample. The primary question was whether being an Ecstasy user (E-user) was predictive of having clinically deficient memory performance compared to a healthy control group.

METHODS:

WLT data were pooled from four experimental MDMA studies that compared memory performance during placebo and MDMA intoxication. Control data were taken from healthy volunteers with no drug use history who completed the WLT as part of a placebo-controlled clinical trial. This resulted in a sample size of 65 E-users and 65 age- and gender-matched healthy drug-naïve controls. All participants were recruited by similar means and were tested at the same testing facilities using identical standard operating procedures. Data were analyzed using linear mixed-effects models, Bayes factor, and logistic regressions.

RESULTS:

Findings were that verbal memory performance of placebo-treated E-users did not differ from that of controls, and there was substantial evidence in favor of the null hypothesis. History of use was not predictive of memory impairment. During MDMA intoxication of E-users, verbal memory was impaired.

CONCLUSION:

The combination of the acute and long-term findings demonstrates that, while clinically relevant memory impairment is present during intoxication, it is absent during abstinence. This suggests that use of Ecstasy/MDMA does not lead to clinically deficient memory performance in the long term. Additionally, it has to be investigated whether the current findings apply to more complex cognitive measures in diverse ‘user categories’ using a combination of genetics, imaging techniques and neuropsychological assessments.

Kuypers, K. P., Theunissen, E. L., van Wel, J. H., Perna, E. B. D. S. F., Linssen, A., Sambeth, A., … & Ramaekers, J. G. (2016). Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective. PloS one, 11(2), e0149438. http://dx.doi.org/10.1371/journal.pone.0149438

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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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Effects of MDMA Injections on the Behavior of Socially-Housed Long-Tailed Macaques (Macaca fascicularis)

February 3, 2016 / MDMA, Other subjects, Papers, Psychology, Publications / By / , , ,

Abstract

3,4-methylenedioxy-N-methyl amphetamine (MDMA) is one of the few known molecules to increase human and rodent prosocial behaviors. However, this effect has never been assessed on the social behavior of non-human primates. In our study, we subcutaneously injected three different doses of MDMA (1.0, 1.5 or 2.0mg/kg) to a group of three, socially housed, young male long-tailed macaques. More than 200 hours of behavioral data were recorded, during 68 behavioral sessions, by an automatic color-based video device that tracked the 3D positions of each animal and of a toy. This data was then categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play). In addition, received and given social grooming was manually scored. Results show several significant dose-dependent behavioral effects. At 1.5mg/kg only, MDMA induces a significant increase in social grooming behavior, thus confirming the prosocial effect of MDMA in macaques. Additionally, at 1.5 and 2.0 mg/kg MDMA injection substantially decreases foraging behavior, which is consistent with the known anorexigenic effect of this compound. Furthermore, at 2.0 mg/kg MDMA injection induces an increase in locomotor behavior, which is also in accordance with its known stimulant property. Interestingly, MDMA injected at 1.0mg/kg increases the rate of object play, which might be interpreted as a decrease of the inhibition to manipulate a unique object in presence of others, or, as an increase of the intrinsic motivation to manipulate this object. Together, our results support the effectiveness of MDMA to study the complex neurobiology of primates’ social behaviors.

Ballesta, S., Reymond, G., Pozzobon, M., & Duhamel, J. R. (2016). Effects of MDMA Injections on the Behavior of Socially-Housed Long-Tailed Macaques (Macaca fascicularis). PloS one, 11(2), e0147136. http://dx.doi.org/10.1371/journal.pone.0147136
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Oxytocin receptor gene variation predicts subjective responses to MDMA

January 20, 2016 / MDMA, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , , ,

Abstract

3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) enhances desire to socialize and feelings of empathy, which are thought to be related to increased oxytocin levels. Thus, variation in the oxytocin receptor gene (OXTR) may influence responses to the drug. Here we examined the influence of a single OXTR nucleotide polymorphism (SNP) on responses to MDMA in humans. Based on findings that carriers of the A allele at rs53576 exhibit reduced sensitivity to oxytocin-induced social behavior, we hypothesized that these individuals would show reduced subjective responses to MDMA, including sociability. In this 3-session, double blind, within-subjects study, healthy volunteers with past MDMA experience (N = 68) received a MDMA (0, 0.75 mg/kg and 1.5 mg/kg) and provided self-report ratings of sociability, anxiety, and drug effects. These responses were examined in relation to rs53576. MDMA (1.5 mg/kg) did not increase sociability in individuals with the A/A genotype as it did in G allele carriers. The genotypic groups did not differ in responses at the lower MDMA dose, or in cardiovascular or other subjective responses. These findings are consistent with the idea that MDMA-induced sociability is mediated by oxytocin, and that variation in the oxytocin receptor gene may influence responses to the drug.

Bershad, A. K., Weafer, J. J., Kirkpatrick, M. G., Wardle, M. C., Miller, M. A., & de Wit, H. (2016). Oxytocin receptor gene variation predicts subjective responses to MDMA. Social neuroscience. http://dx.doi.org/10.1080/17470919.2016.1143026

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Psychedelic Medicine: Is it a False Dawn or a Renaissance?

January 1, 2016 / Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Other substances, Papers, Psychiatry, Psychotherapy, Publications / By /

Abstract

Aim: There has been renewed interest in “psychedelics” in the last 10 years and their usefulness in Psychiatric treatment explored. The aim of the article is to highlight current controversies surrounding psychedelics medicinal uses and address imminent international legislation changes and the effects these will have in the face of new evidence showing their efficacy in some resistant mental health diagnoses.
Conclusion: Possession and use of drugs that fall under the category of psychedelics is criminalized universally. They are considered to have no medical use and high potential for abuse. The dissensus about their use in treatment of mental disorders continues and there is a lack of compelling evidence proving their efficacy. Their use has far been limited to a handful of research centers, due to their criminalization, but the evidence is building and becoming very hard to ignore.
Ali, A. Y. (2016). Psychedelic Medicine: Is it a False Dawn or a Renaissance?. International Journal of Emergency Mental Health and Human Resilience, 2016.
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As Molly Takes The Party Toll: MDMA Toxicity Presenting With Pulmonary Hemorrhage

January 1, 2016 / MDMA, Medicine, Other subjects, Papers, Publications / By / , , ,

Khalid, F., Kowsika, S., Ghobrial, I., & Rehman, S. (2016). As Molly Takes The Party Toll: MDMA Toxicity Presenting With Pulmonary Hemorrhage. In A46. LUNG DISEASE DUE TO OTC AND ILLICITS: CASE REPORTS (pp. A1616-A1616). American Thoracic Society.
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Influence of caffeine on 3,4-methylenedioxymethamphetamine-induced dopaminergic neuron degeneration and neuroinflammation is age-dependent

January 1, 2016 / MDMA, Neuroscience, Other subjects, Papers, Psychopharmacology, Publications, Safety / By / , , , , , ,

Abstract

Previous studies have demonstrated that caffeine administration to adult mice potentiates glial activation induced by 3,4-methylenedioxymethamphetamine (MDMA). As neuroinflammatory response seems to correlate with neurodegeneration, and the young brain is particularly vulnerable to neurotoxicity, we evaluated dopamine neuron degeneration and glial activation in the caudate-putamen (CPu) and substantia nigra pars compacta (SNc) of adolescent and adult mice. Mice were treated with MDMA (4 × 20 mg/kg), alone or with caffeine (10 mg/kg). Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, neuronal nitric oxide synthase (nNOS) were evaluated in CPu, whereas tyrosine hydroxylase (TH), glial fibrillary acidic protein, and CD11b were evaluated in CPu and SNc by immunohistochemistry. MDMA decreased TH in SNc of both adolescent and adult mice, whereas TH-positive fibers in CPu were only decreased in adults. In CPu of adolescent mice, caffeine potentiated MDMA-induced glial fibrillary acidic protein without altering CD11b, whereas in SNc caffeine did not influence MDMA-induced glial activation. nNOS, IL-1β, and TNF-α were increased by MDMA in CPu of adults, whereas in adolescents, levels were only elevated after combined MDMA plus caffeine. Caffeine alone modified only nNOS. Results suggest that the use of MDMA in association with caffeine during adolescence may exacerbate the neurotoxicity and neuroinflammation elicited by MDMA. Previous studies have demonstrated that caffeine potentiated glial activation induced by 3,4-methylenedioxymethamphetamine (MDMA) in adult mice. In this study, caffeine was shown to potentiate MDMA-induced dopamine neuron degeneration in substantia nigra pars compacta, astrogliosis, and TNF-α levels in caudate-putamen of adolescent mice. Results suggest that combined use of MDMA plus caffeine during adolescence may worsen the neurotoxicity and neuroinflammation elicited by MDMA.

Frau, L., Costa, G., Porceddu, P. F., Khairnar, A., Castelli, M. P., Ennas, M. G., … & Morelli, M. (2016). Influence of caffeine on 3, 4‐methylenedioxymethamphetamine‐induced dopaminergic neuron degeneration and neuroinflammation is age‐dependent. Journal of neurochemistry, 136(1), 148-162. http://dx.doi.org/10.1111/jnc.13377

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Neuroimaging in moderate MDMA use: A systematic review

December 30, 2015 / MDMA, Neuroscience, Papers, Publications, Safety / By / , , , , , ,

Abstract

MDMA (“ecstasy”) is widely used as a recreational drug, although there has been some debate about its neurotoxic effects in humans. However, most studies have investigated subjects with heavy use patterns, and the effects of transient MDMA use are unclear. In this review, we therefore focus on subjects with moderate use patterns, in order to assess the evidence for harmful effects. We searched for studies applying neuroimaging techniques in man. Studies were included if they provided at least one group with an average of <50 lifetime episodes of ecstasy use or an average lifetime consumption of <100 ecstasy tablets. All studies published before July 2015 were included. Of the 250 studies identified in the database search, 19 were included.

There is no convincing evidence that moderate MDMA use is associated with structural or functional brain alterations in neuroimaging measures. The lack of significant results was associated with high methodological heterogeneity in terms of dosages and co-consumption of other drugs, low quality of studies and small sample sizes.

Mueller, F., Lenz, C., Steiner, M., Dolder, P. C., Walter, M., Lang, U. E., … & Borgwardt, S. (2016). Neuroimaging in moderate MDMA use: A systematic review. Neuroscience & Biobehavioral Reviews, 62, 21-34. http://dx.doi.org/10.1016/j.neubiorev.2015.12.010
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The Psychopharmacology of ±3,4 Methylenedioxymethamphetamine and its Role in the Treatment of Posttraumatic Stress Disorder

November 18, 2015 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By /

Abstract

Prior to 1985, ± 3,4-methylenedioxymethamphetamine (MDMA) was readily used as a psychotherapeutic adjunct. As MDMA became popular in treating various psychiatric illnesses by mental health professionals, the public started to abuse the MDMA-containing recreational drug “ecstasy.” This alarmed the DEA, which led to emergency scheduling of MDMA as a Schedule I drug. Due to its scheduling in 1985, human research and clinical use has been limited. The majority of research on MDMA has been focused on the drug’s potential harmful effects rather than its possible therapeutic effects. The limitations on retrospective human studies and preclinical animal models of MDMA neurotoxicity are examined in this analysis. New research has shown that MDMA, used as a catalyst in psychotherapy, is effective in treating posttraumatic stress disorder (PTSD). This review also examines the psychopharmacological basis for the efficacy of MDMA-assisted psychotherapy. Specifically, the brain regions involved with both PTSD and those activated by MDMA (i.e., amygdala, anterior cingulate cortex, and hippocampus) are examined. Also, the possible neurochemical mechanisms involved in MDMA’s efficacy in treating PTSD are reviewed.

Amoroso, T. (2015). The Psychopharmacology of±3, 4 Methylenedioxymethamphetamine and its Role in the Treatment of Posttraumatic Stress Disorder. Journal of Psychoactive Drugs, 1-8. http://dx.doi.org/10.1080/02791072.2015.1094156

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