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MDMA

Recreational 3,4-methylenedioxy-N-methylamphetamine (MDMA) or 'ecstasy' and self-focused compassion: Preliminary steps in the development of a therapeutic psychopharmacology of contemplative practices

September 1, 2015 / MDMA, Papers, Personality, Psychology, Publications / By / , , , , , ,

Abstract

3,4-methylenedioxy-N-methylamphetamine (MDMA) produces diverse pro-social effects. Cognitive training methods rooted in Eastern contemplative practices also produce these effects through the development of a compassionate mindset. Given this similarity, we propose that one potential mechanism of action of MDMA in psychotherapy is through enhancing effects on intrapersonal attitudes (i.e. pro-social attitudes towards the self). We provide a preliminary test of this idea. Recreational MDMA (ecstasy) users were tested on two occasions, having consumed or not consumed ecstasy. Self-critical and self-compassionate responses to self-threatening scenarios were assessed before (T1) and after (T2) ecstasy use (or non-use), and then after compassionate imagery (T3). Moderating roles of dispositional self-criticism and avoidant attachment were examined. Separately, compassionate imagery and ecstasy produced similar sociotropic effects, as well as increases in self-compassion and reductions in self-criticism. Higher attachment-related avoidance was associated with additive effects of compassionate imagery and ecstasy on self-compassion. Findings were in line with MDMA’s neuropharmacological profile, its phenomenological effects and its proposed adjunctive use in psychotherapy. However, although conditions were balanced, the experiment was non-blind and MDMA dose/purity was not determined. Controlled studies with pharmaceutically pure MDMA are still needed to test these effects rigorously.

Kamboj, S. K., Kilford, E. J., Minchin, S., Moss, A., Lawn, W., Das, R. K., … & Freeman, T. P. (2015). Recreational 3, 4-methylenedioxy-N-methylamphetamine (MDMA) or ‘ecstasy’and self-focused compassion: preliminary steps in the development of a therapeutic psychopharmacology of contemplative practices. Journal of Psychopharmacology, 0269881115587143.

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MDMA, cannabis, and cocaine produce acute dissociative symptoms

August 30, 2015 / MDMA, Other subjects, Other substances, Papers, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. We explored the dissociative potential of three recreational drugs (3,4-methylenedioxymethamphetamine (MDMA), cannabis, and cocaine) during intoxication and compared their effects to literature reports of dissociative states in various samples. Two placebo-controlled studies were conducted. In Study 1 (N=16), participants received single doses of 25, 50, and 100 mg of MDMA, and placebo. In Study 2 (N=21), cannabis (THC 300 µg/kg), cocaine (HCl 300 mg), and placebo were administered. Dissociative symptoms as measured with the Clinician-Administered Dissociative States Scale (CADSS) significantly increased under the influence of MDMA and cannabis. To a lesser extent, this was also true for cocaine. Dissociative symptoms following MDMA and cannabis largely exceeded those observed in schizophrenia patients, were comparable with those observed in Special Forces soldiers undergoing survival training, but were lower compared with ketamine-induced dissociation. Cocaine produced dissociative symptoms that were comparable with those observed in schizophrenia patients, but markedly less than those in Special Forces soldiers and ketamine users. Thus, MDMA and cannabis can produce dissociative symptoms that resemble dissociative pathology. The study of drug induced dissociation is important, because it may shed light on the mechanisms involved in dissociative psychopathology.

van Heugten-Van der Kloet, D., Giesbrecht, T., van Wel, J., Bosker, W. M., Kuypers, K. P., Theunissen, E. L., … & Ramaekers, J. G. (2015). MDMA, cannabis, and cocaine produce acute dissociative symptoms. Psychiatry research, 228(3), 907-912. http://dx.doi.org/10.1016/j.psychres.2015.04.028

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5-HTTLPR Genotype Moderates the Effects of Past Ecstasy Use on Verbal Memory Performance in Adolescent and Emerging Adults: A Pilot Study

July 31, 2015 / MDMA, Neuroscience, Other subjects, Papers, Psychopharmacology, Publications / By / , , , ,

Abstract

OBJECTIVE: Ecstasy use is associated with memory deficits. Serotonin transporter gene (5-HTTLPR) polymorphisms have been linked with memory function in healthy samples. The present pilot study investigated the influence of 5-HTTLPR polymorphisms on memory performance in ecstasy users, marijuana-using controls, and non-drug-using controls, after a minimum of 7 days of abstinence.

METHOD: Data were collected from 116 young adults (18-25 years-old), including 45 controls, 42 marijuana users, and 29 ecstasy users, and were balanced for 5-HTTLPR genotype. Participants were abstinent seven days prior to completing memory testing. Three MANCOVAs and one ANCOVA were run to examine whether drug group, 5-HTTLPR genotype, and their interactions predicted verbal and visual memory after controlling for gender, past year alcohol use, other drug use, and nicotine cotinine levels.

RESULTS: MANCOVA and ANCOVA analysis revealed a significant interaction between drug group and genotype (p = .03) such that ecstasy users with the L/L genotype performed significantly worse on CVLT-2 total recall (p = .05), short (p = .008) and long delay free recall (p = .01), and recognition (p = .006), with the reverse pattern found in controls. Ecstasy did not significantly predict visual memory. 5-HTTLPR genotype significantly predicted memory for faces (p = .02); short allele carriers performed better than those with L/L genotype.

CONCLUSIONS: 5-HTTLPR genotype moderated the effects of ecstasy on verbal memory, with L/L carriers performing worse compared to controls. Future research should continue to examine individual differences in ecstasy’s impact on neurocognitive performance as well as relationships with neuronal structure. Additional screening and prevention efforts focused on adolescents and emerging adults are necessary to prevent ecstasy consumption.

Wright, N. E., Strong, J. A., Gilbart, E. R., Shollenbarger, S. G., & Lisdahl, K. M. (2015). 5-HTTLPR Genotype Moderates the Effects of Past Ecstasy Use on Verbal Memory Performance in Adolescent and Emerging Adults: A Pilot Study. PloS one, 10(7), e0134708. http://dx.doi.org/10.1371/journal.pone.0134708

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Greater sexual risk-taking in female and male recreational MDMA/ecstasy users compared with alcohol drinkers: a questionnaire study

July 30, 2015 / MDMA, Other subjects, Papers, Publications, Sociology / By / ,

Abstract

AIMS: Previous studies have shown increased sexual risk-taking in experienced MDMA/ecstasy users. The main objectives of this study were to compare levels of sexual risk-taking between a young student sample of predominantly heterosexual MDMA users and alcohol-drinker controls and investigate potential gender differences.

METHODS: Recreational drug use and sexual risk questionnaires were completed by 20 MDMA users (10 females, 10 males) and 20 non-user controls (10 females, 10 males). They were predominantly university students, aged between 20-22 years, mainly heterosexual (n = 37), with three bisexual participants.

RESULTS: MDMA users displayed significantly greater levels of sexual risk-taking than the alcohol-drinker controls. It involved significantly higher rates of casual sex, non-condom use during sex, and penetrative sexual risks. This increase in sexual riskiness occurred to a similar extent in males and females.

CONCLUSIONS: These findings indicate that both female and male ecstasy/MDMA users reported more risky sexual behaviours, than the non-user controls. Further research into the sexual behaviour and sexual risk-taking of heterosexual MDMA users should be conducted because much of the past literature has focused on homosexual participants.

May, A. L., & Parrott, A. C. (2015). Greater sexual risk‐taking in female and male recreational MDMA/ecstasy users compared with alcohol drinkers: a questionnaire study. Human Psychopharmacology: Clinical and Experimental, 30(4), 272-275. http://dx.doi.org/10.1002/hup.2432

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The potential utility of some legal highs in CNS disorders

July 29, 2015 / Anxiety disorders / PTSD, Depression, Ketamine, LSD, MDMA, Medicine, Mushrooms / Psilocybin, Other subjects, Other substances, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Substance Use Disorder / By / ,

Abstract

Over the last decade there has been an explosion of new drugs of abuse, so called legal highs or novel psychoactive substances (NPS). Many of these abused drugs have unknown pharmacology, but their biological effects can be anticipated from their molecular structure and possibly also from online user reports. When considered with the findings that some prescription medications are increasingly abused and that some abused drugs have been tested clinically one could argue that there has been a blurring of the line between drugs of abuse and clinically used drugs. In this review we examine these legal highs/NPS and consider whether, based on their known or predicted pharmacology, some might have the potential to be clinically useful in CNS disorders.

Davidson, C., & Schifano, F. (2015). The potential utility of some legal highs in CNS disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. https://dx.doi.org/10.1016/j.pnpbp.2015.07.010
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Developmental outcomes of 3,4-methylenedioxymethamphetamine (ecstasy)-exposed infants in the UK

July 28, 2015 / MDMA, Neuroscience, Other subjects, Papers, Psychiatry, Publications, Safety / By / , , , , , ,

Abstract

OBJECTIVE: This paper aims to review findings from a longitudinal study of prenatal methylenedioxymethamphetamine (MDMA, “ecstasy”) on infant development.

METHODS: In a prospective, longitudinal cohort design, we followed 28 MDMA-exposed and 68 non-MDMA-exposed infants from birth to 2 years of age. Women recruited voluntarily into a study of recreational drug use during pregnancy were interviewed to obtain type, frequency, and amount of recreational drug use. Their children were followed for a 2-year period after birth. A large number of drug and environmental covariates were controlled. Infants were seen at 1, 4, 12, 18, and 24 months using standardized normative tests of mental and motor development.

RESULTS: There were no differences between MDMA-exposed and non-MDMA-exposed infants at birth except that MDMA-exposed infants were more likely to be male. Motor delays were evident in MDMA infants at each age and amount of MDMA exposure predicted motor deficits at 12 months in a dose-dependent fashion.

CONCLUSIONS: Prenatal MDMA exposure is related to fine and gross motor delays in the first 2 years of life. Follow-up studies are needed to determine long-term effects.

Singer, L. T., Moore, D. G., Min, M. O., Goodwin, J., Turner, J. J., Fulton, S., & Parrott, A. C. (2015). Developmental outcomes of 3, 4‐methylenedioxymethamphetamine (ecstasy)‐exposed infants in the UK. Human Psychopharmacology: Clinical and Experimental, 30(4), 290-294. http://dx.doi.org/0.1002/hup.2459

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Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities

July 14, 2015 / DMT, LSD, MDMA, Medicine, Neuroscience, Other substances, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By /

Abstract

Classical psychedelics are psychoactive substances, which, besides their psychopharmacological activity, have also been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation, and cell survival via activating NF-κB and mitogen-activated protein kinases. Recently, several neurotransmitter receptors involved in the pharmacology of psychedelics, such as serotonin and sigma-1 receptors, have also been shown to play crucial roles in numerous immunological processes. This emerging field also offers promising treatment modalities in the therapy of various diseases including autoimmune and chronic inflammatory conditions, infections, and cancer. However, the scarcity of available review literature renders the topic unclear and obscure, mostly posing psychedelics as illicit drugs of abuse and not as physiologically relevant molecules or as possible agents of future pharmacotherapies. In this paper, the immunomodulatory potential of classical serotonergic psychedelics, including N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-iodoamphetamine, and 3,4-methylenedioxy-methamphetamine will be discussed from a perspective of molecular immunology and pharmacology. Special attention will be given to the functional interaction of serotonin and sigma-1 receptors and their cross-talk with toll-like and RIG-I-like pattern-recognition receptor-mediated signaling. Furthermore, novel approaches will be suggested feasible for the treatment of diseases with chronic inflammatory etiology and pathology, such as atherosclerosis, rheumatoid arthritis, multiple sclerosis, schizophrenia, depression, and Alzheimer’s disease.

Szabo, A. Psychedelics and immunomodulation: Novel approaches and therapeutic opportunities. Frontiers in Immunology, 0. https://dx.doi.org/10.3389/fimmu.2015.00358
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Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers

June 9, 2015 / MDMA, Neuroscience, Other subjects, Papers, Psychopharmacology, Publications / By / ,

Abstract

While hippocampus is a brain region particularly susceptible to the effects of MDMA, the cellular and molecular changes induced by MDMA are still to be fully elucidated, being the dosage regimen, the species and the developmental stage under study great variables. This study compared the effects of one and four days of MDMA administration following a binge paradigm (3×5 mg/kg, i.p., every 2 h) on inducing hippocampal neurochemical changes in adolescent (PND 37) and young adult (PND 58) rats. The results showed that chronic MDMA caused hippocampal protein deficits in adolescent and young adult rats at different levels: (1) impaired serotonergic (5-HT2A and 5-HT2C post-synaptic receptors) and GABAergic (GAD2 enzyme) signaling, and (2) decreased structural cytoskeletal neurofilament proteins (NF-H, NF-M and NF-L). Interestingly, these effects were not accompanied by an increase in apoptotic markers. In fact, chronic MDMA inhibited proteins of the apoptotic pathway (i.e., pro-apoptotic FADD, Bax and cytochrome c) leading to an inhibition of cell death markers (i.e., p-JNK1/2, cleavage of PARP-1) and suggesting regulatory mechanisms in response to the neurochemical changes caused by the drug. The data, together with the observed lack of GFAP activation, support the view that chronic MDMA effects, regardless of the rat developmental age, extends beyond neurotransmitter systems to impair other hippocampal structural cell markers. Interestingly, inhibitory changes in proteins from the apoptotic pathway might be taking place to overcome the protein deficits caused by MDMA.

García-Cabrerizo, R., & García-Fuster, M. J. (2015). Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers. Neurotoxicology, 49, 104-113. http://dx.doi.org/10.1016/j.neuro.2015.06.001

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MDMA for the treatment of mood disorder: all talk no substance?

June 1, 2015 / Depression, MDMA, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / ,

Abstract

BACKGROUND:

Unipolar depression is the third highest contributor to the global burden of disease, yet current pharmacotherapies typically take about 6 weeks to have an effect. A rapid-onset agent is an attractive prospect, not only to alleviate symptoms before first-line antidepressants display therapeutic action, but as a further treatment option in nonresponsive cases. It has been suggested that 3,4-methylene-dioxymethamphetamine (MDMA) could play a part in the treatment of depression, either as a rapid-onset pharmacological agent or as an adjunct to psychotherapy. Whilst these hypotheses are in keeping with the monoamine theory of depression and the principles surrounding psychotherapy, explicit experimental evidence of an antidepressant effect of MDMA has rarely been established.

AIMS:

To address the hypothesis surrounding MDMA as a rapid-onset antidepressant by examining pharmacological, psychological and behavioural studies. We consider whether this therapy could be safe by looking at the translation of neurotoxicity data from animals to humans.

METHOD:

A literature review of the evidence supporting this hypothesis was performed.

CONCLUSIONS:

The pharmacology of MDMA offers a promising target as a rapid-onset agent and MDMA is currently being investigated for use in psychotherapy in anxiety disorders; translation from these studies for use in depression may be possible. However, experimental evidence and safety analysis are insufficient to confirm or reject this theory at present.

Patel, R., & Titheradge, D. (2015). MDMA for the treatment of mood disorder: all talk no substance?. Therapeutic Advances in Psychopharmacology, 2045125315583786. https://dx.doi.org/10.1177/2045125315583786
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Recreational 3,4-methylenedioxy-N-methylamphetamine (MDMA) or ‘ecstasy’ and self-focused compassion: Preliminary steps in the development of a therapeutic psychopharmacology of contemplative practices.

May 18, 2015 / MDMA, Papers, Personal development, Psychiatry, Psychology, Publications / By / , , , , , ,

Abstract

3,4-methylenedioxy-N-methylamphetamine (MDMA) produces diverse pro-social effects. Cognitive training methods rooted in Eastern contemplative practices also produce these effects through the development of a compassionate mindset. Given this similarity, we propose that one potential mechanism of action of MDMA in psychotherapy is through enhancing effects on intrapersonal attitudes (i.e. pro-social attitudes towards the self). We provide a preliminary test of this idea. Recreational MDMA (ecstasy) users were tested on two occasions, having consumed or not consumed ecstasy. Self-critical and self-compassionate responses to self-threatening scenarios were assessed before (T1) and after (T2) ecstasy use (or non-use), and then after compassionate imagery (T3). Moderating roles of dispositional self-criticism and avoidant attachment were examined. Separately, compassionate imagery and ecstasy produced similar sociotropic effects, as well as increases in self-compassion and reductions in self-criticism. Higher attachment-related avoidance was associated with additive effects of compassionate imagery and ecstasy on self-compassion. Findings were in line with MDMA’s neuropharmacological profile, its phenomenological effects and its proposed adjunctive use in psychotherapy. However, although conditions were balanced, the experiment was non-blind and MDMA dose/purity was not determined. Controlled studies with pharmaceutically pure MDMA are still needed to test these effects rigorously.

Kamboj, S. K., Kilford, E. J., Minchin, S., Moss, A., Lawn, W., Das, R. K., … & Freeman, T. P. (2015). Recreational 3, 4-methylenedioxy-N-methylamphetamine (MDMA) or ‘ecstasy’and self-focused compassion: Preliminary steps in the development of a therapeutic psychopharmacology of contemplative practices. Journal of Psychopharmacology, 0269881115587143.
Link to full text