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MDMA

Depressive mood ratings are reduced by MDMA in female polydrug ecstasy users homozygous for the l-allele of the serotonin transporter

January 18, 2018 / MDMA, Neuroscience, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

MDMA exerts its main effects via the serotonergic system and the serotonin transporter. The gene coding for this transporter determines the expression rate of the transporter. Previously it was shown that healthy individuals with the short allelic variant (‘s-group’) of the 5-HTTLPR-polymorphism displayed more anxiety and negative mood, and had a lower transcriptional efficiency compared to individuals who are homozygous for the l-allele (‘l-group’). The present study aimed to investigate the role of the 5-HTTLPR polymorphism in MDMA-induced mood effects. Four placebo-controlled, within-subject studies were pooled, including in total 63 polydrug ecstasy users (Ns-group = 48; Nl-group = 15) receiving MDMA 75 mg and placebo on two test days, separated by minimally 7 days. Mood was assessed by means of the Profile of Mood States. Findings showed that MDMA induced -independent of sex- a positive mood state, and as a side effect also increased two negative affect states, anxiety and confusion. Anxiety ratings were higher in the l-group and independent of treatment or sex. Depression ratings were lowered by MDMA in the female l-group. Findings indicate that the MDMA-induced reduction in self-rated depressive feelings is sex- and genotype-dependent, with females homozygous for the l-allele showing this beneficial effect.
Kuypers, K. P. C., de la Torre, R., Farre, M., Xicota, L., Perna, E. D. S. F., Theunissen, E. L., & Ramaekers, J. G. (2018). Depressive mood ratings are reduced by MDMA in female polydrug ecstasy users homozygous for the l-allele of the serotonin transporter. Scientific reports, 8(1), 1061. 10.1038/s41598-018-19618-1
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Key interindividual determinants in MDMA pharmacodynamics.

January 16, 2018 / MDMA, Medicine, Papers, Psychology, Psychotherapy, Publications, Safety / By / , , , ,

Abstract

MDMA, 3,4-methylenedioxymethamphetamine, is a synthetic phenethylamine derivative with structural and pharmacological similarities to both amphetamines and mescaline. MDMA produces characteristic amphetamine-like actions (euphoria, well-being), increases empathy, and induces pro-social effects that seem to motivate its recreational consumption and provide a basis for its potential therapeutic use. Areas covered: The aim of this review is to present the main interindividual determinants in MDMA pharmacodynamics. The principal sources of pharmacodynamic variability are reviewed, with special emphasis on sex-gender, race-ethnicity, genetic differences, interactions, and MDMA acute toxicity, as well as possible therapeutic use. Expert opinion: Acute MDMA effects are more pronounced in women than they are in men. Very limited data on the relationship between race-ethnicity and MDMA effects are available. MDMA metabolism includes some polymorphic enzymes that can slightly modify plasma concentrations and effects. Although a considerable number of studies exist about the acute effects of MDMA, the small number of subjects in each trial limits evaluation of the different interindividual factors and does not permit a clear conclusion about their influence. These issues should be considered when studying possible MDMA therapeutic use.
Papaseit, E., Torrens, M., Pérez-Mañá, C., Muga, R., & Farré, M. (2018). Key interindividual determinants in MDMA pharmacodynamics. Expert opinion on drug metabolism & toxicology, (just-accepted). 10.1080/17425255.2018.1424832
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Current Perspective on MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder

January 6, 2018 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / ,

Abstract

The present paper discusses the current literature with regard to substance-assisted psychotherapy with Methylenedioxymethamphetamine (MDMA) for posttraumatic stress disorder (PTSD). The aim of the paper is to give a comprehensive overview of the development from MDMA’s early application in psychotherapy to its present and future role in the treatment of PTSD. It is further attempted to increase the attention for MDMA’s therapeutic potential by providing a thorough depiction of the scientific evidence regarding its theorized mechanism of action and potential harms of its application in the clinical setting (e.g., misattribution of therapeutic gains to medication instead of psychological changes). Empirical support for the use of MDMA-assisted psychotherapy, including the randomized, double-blind, placebo-controlled trails that have been conducted since 2008, is discussed. Thus far, an overall remission rate of 66.2% and low rates of adverse effects have been found in the six phase two trials conducted in clinical settings with 105 blinded subjects with chronic PTSD. The results seem to support MDMA’s safe and effective use as an adjunct to psychotherapy. Even though preliminary studies may look promising, more studies of its application in a psychotherapeutic context are needed in order to establish MDMA as a potential adjunct to therapy.

Thal, S. B., & Lommen, M. J. (2018). Current Perspective on MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder. Journal of Contemporary Psychotherapy, 1-10. 10.1007/s10879-017-9379-2
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First Network Meeting for European MDMA Researchers & Therapists

December 6, 2021 / Articles, Events, MDMA, Publications, Research / By

Endegeest CastleIn early December, the first network meeting for European MDMA researchers and therapists was held in scenic Castle Endegeest, near the city of Leiden in the Netherlands.

The meeting was organised by OPEN and the Dutch therapist team responsible for conducting the first Dutch open-label study for MDMA-assisted psychotherapy for people suffering from severe PTSD. MAPS provided additional support for this event.
The group consisted of psychologists and psychiatrists from seven countries: Wales, England, Czech Republic, Germany, Israel and Canada besides the Dutch. This was a small and intimate meeting, with the primary aim to build a network of like-minded European MDMA-therapists. Saturday was a day full of lectures, sharing of research plans and objectives, and discussions on therapeutic modalities. Rick Doblin, executive director of MAPS called in from the American West Coast to share what the future holds in terms of clinical trials and regulatory processes, providing an inspirational message of support. The day ended with a screening of the Israeli documentary Trip of Compassion, on the Israeli phase 2 clinical trials for MDMA-assisted treatment for PTSD. One of the therapists involved in the study was present to provide context, to explain what was happening during the session from the therapist’s perspective, and to answer questions from the audience. This powerful document was the highlight of the day for most people.
On the last day, participants were able to undergo a one hour music therapy session, facilitated by a leading specialist, which turned out to be a meaningful and insightful experience for most people. The session provided not only personal insights but also gave the participants specific ideas on the role of music and specific sounds and songs. An impressive testament to the power of music in the right setting.
Finally, the first draft to establish a platform to help coordinate and facilitate MDMA-related research and therapy was well received by participants and will be expanded and presented in the near future.

Acute effects of methylphenidate, modafinil and MDMA on negative emotion processing

December 1, 2017 / MDMA, Other subjects, Papers, Psychology, Publications / By / , , , , ,

Abstract

BACKGROUND:
Stimulants such as methylphenidate (MPH) and modafinil are frequently used as cognitive enhancers in healthy people, whereas 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is proposed to enhance mood and empathy in healthy subjects. However, comparative data on the effects of MPH and modafinil on negative emotions in healthy subjects have been widely missing. The aim of this study was to compare the acute effects of MPH and modafinil on the neural correlates of fearful face processing using MDMA as a positive control.
METHODS:
Using a double-blind within-subject placebo-controlled cross-over design, 60 mg MPH, 600 mg modafinil, and 125 mg MDMA were administrated to 22 healthy subjects, while performing an event-related fMRI task to assess brain activation in response to fearful faces. Negative mood states were assessed with the State-Trait Anxiety Inventory and subjective ratings.
RESULTS:
Relative to placebo, modafinil, but not MPH or MDMA, increased brain activation within a limbic-cortical-striatal-pallidal-thalamic circuit during fearful face processing. Modafinil but not MPH also increased amydgala responses to fearful faces compared with MDMA. Furthermore, activation in the middle and inferior frontal gyrus in response to fearful faces correlated positively with subjective feelings of fearfulness and depressiveness after modafinil administration.
CONCLUSIONS:
In spite of the cognitive enhancement effects of 600 mg modafinil in healthy people, potential adverse effects on emotion processing should be considered.
Schmidt, A., Müller, F., Dolder, P. C., Schmid, Y., Zanchi, D., Egloff, L., … & Borgwardt, S. (2017). Acute effects of methylphenidate, modafinil and MDMA on negative emotion processing. International Journal of Neuropsychopharmacology, pyx112. 10.1093/ijnp/pyx112
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Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine

November 25, 2017 / Depression, Ketamine, MDMA, Papers, Psychiatry, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Rationale

Clinical data with 3,4-methylenedioxymethamphetamine (MDMA) in post-traumatic stress disorder (PTSD) patients recently stimulated interest on the potential therapeutic use of psychedelics in disorders characterized by maladaptive memories, including substance use disorders (SUD). The rationale for the use of MDMA in PTSD and SUD is being extended to a broader beneficial “psychedelic effect,” which is supporting further clinical investigations, in spite of the lack of mechanistic hypothesis. Considering that the retrieval of emotional memories reactivates specific brain mechanisms vulnerable to inhibition, interference, or strengthening (i.e., the reconsolidation process), it was proposed that the ability to retrieve and change these maladaptive memories might be a novel intervention for PTSD and SUD. The mechanisms underlying MDMA effects indicate memory reconsolidation modulation as a hypothetical process underlying its efficacy.

Objective

Mechanistic and clinical studies with other two classes of psychedelic substances, namely cannabinoids and ketamine, are providing data in support of a potential use in PTSD and SUD based on the modulation of traumatic and appetitive memory reconsolidation, respectively. Here, we review preclinical and clinical data on cannabinoids and ketamine effects on biobehavioral processes related to the reconsolidation of maladaptive memories.

Results

We report the findings supporting (or not) the working hypothesis linking the potential therapeutic effect of these substances to the underlying reconsolidation process. We also proposed possible approaches for testing the use of these two classes of drugs within the current paradigm of reconsolidation memory inhibition.

Conclusions

Metaplasticity may be the process in common between cannabinoids and ketamine/ketamine-like substance effects on the mediation and potential manipulation of maladaptive memories.

Fattore, L., Piva, A., Zanda, M. T., Fumagalli, G., & Chiamulera, C. (2017). Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine. Psychopharmacology, 1-13. 10.1007/s00213-017-4793-4
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Progress and promise for the MDMA drug development program

November 20, 2017 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , ,

Abstract

Pharmacotherapy is often used to target symptoms of posttraumatic stress disorder (PTSD), but does not provide definitive treatment, and side effects of daily medication are often problematic. Trauma-focused psychotherapies are more likely than drug treatment to achieve PTSD remission, but have high dropout rates and ineffective for a large percentage of patients. Therefore, research into drugs that might increase the effectiveness of psychotherapy is a logical avenue of investigation. The most promising drug studied as a catalyst to psychotherapy for PTSD thus far is 3,4-methylenedioxymethamphetamine (MDMA), commonly known as the recreational drug “Ecstasy.” MDMA stimulates the release of hormones and neurochemicals that affect key brain areas for emotion and memory processing. A series of recently completed phase 2 clinical trials of MDMA-assisted psychotherapy for treatment of PTSD show favorable safety outcomes and large effect sizes that warrant expansion into multi-site phase 3 trials, set to commence in 2018. The nonprofit sponsor of the MDMA drug development program, the Multidisciplinary Association for Psychedelic Studies (MAPS), is supporting these trials to explore whether MDMA, administered on only a few occasions, can increase the effectiveness of psychotherapy. Brain imaging techniques and animal models of fear extinction are elucidating neural mechanisms underlying the robust effects of MDMA on psychological processing; however, much remains to be learned about the complexities of MDMA effects as well as the complexities of PTSD itself.
Feduccia, A. A., Holland, J., & Mithoefer, M. C. (2017). Progress and promise for the MDMA drug development program. Psychopharmacology, 1-11. 10.1007/s00213-017-4779-2
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Studies with psychedelic drugs in human volunteers

November 18, 2017 / DMT, Ketamine, MDMA, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , ,

Abstract

Scientific curiosity and fascination have played a key role in human research with psychedelics along with the hope that perceptual alterations and heightened insight could benefit well-being and play a role in the treatment of various neuropsychiatric disorders. These motivations need to be tempered by a realistic assessment of the hurdles to be cleared for therapeutic use. Development of a psychedelic drug for treatment of a serious psychiatric disorder presents substantial although not insurmountable challenges. While the varied psychedelic agents described in this chapter share some properties, they have a range of pharmacologic effects that are reflected in the gradation in intensity of hallucinogenic effects from the classical agents to DMT, MDMA, ketamine, dextromethorphan and new drugs with activity in the serotonergic system. The common link seems to be serotonergic effects modulated by NMDA and other neurotransmitter effects. The range of hallucinogens suggest that they are distinct pharmacologic agents and will not be equally safe or effective in therapeutic targets. Newly synthesized specific and selective agents modeled on the legacy agents may be worth considering. Defining therapeutic targets that represent unmet medical need, addressing market and commercial issues, and finding treatment settings to safely test and use such drugs make the human testing of psychedelics not only interesting but also very challenging.
Sellers, E. M., Romach, M. K., & Leiderman, D. B. (2017). Studies with psychedelic drugs in human volunteers. Neuropharmacology. 10.1016/j.neuropharm.2017.11.029
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Why MDMA therapy for alcohol use disorder? And why now?

November 7, 2017 / MDMA, Papers, Psychiatry, Psychology, Psychotherapy, Publications, Substance Use Disorder / By /

Abstract

Alcohol use disorder represents a serious clinical, social and personal burden on its sufferers and a significant financial strain on society. Current treatments, both psychological and pharmacological are poor, with high rates of relapse after medical detoxification and dedicated treatment programs. The earliest historical roots of psychedelic drug-assisted psychotherapy in the 1950s were associated with Lysergic acid diethylamide (LSD)-assisted psychotherapy to treat what was then called, alcoholism. But results were varied and psychedelic therapy with LSD and other ‘classical’ psychedelics fell out of favour in the wake of socio-political pressures and cultural changes. A current revisiting of psychedelic clinical research is now targeting substance use disorders – and particularly alcohol use disorder – again. 3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy has never been formally explored as a treatment for any form of substance use disorder. But in recent years MDMA has risen in prominence as an agent to treat posttraumatic stress disorder (PTSD). With its unique receptor profile and a relatively well-tolerated subjective experience of drug effects when used clinically, MDMA Therapy is ideally suited to allow a patient to explore and address painful memories without being overwhelmed by negative affect. Given that alcohol use disorder is so often associated with early traumatic experiences, the author is proposing in a current on-going UK-based study that patients with alcohol use disorder who have undergone a medical detoxification from alcohol might benefit from a course of MDMA-assisted psychotherapy.

Sessa, B. (2017). Why MDMA therapy for alcohol use disorder? And why now?. Neuropharmacology. 10.1016/j.neuropharm.2017.11.004
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Additive Effects of 3,4-Methylenedioxymethamphetamine (MDMA) and Compassionate Imagery on Self-Compassion in Recreational Users of Ecstasy

November 4, 2017 / MDMA, Papers, Personality, Psychology, Psychotherapy, Publications / By / , , , , , ,

Abstract

3,4-Methylenedioxymethylamphetamine (MDMA;‘ecstasy’) produces prosocial subjective effects that may extend to affiliative feelings towards the self. Behavioural techniques can produce similar self-directed affiliation. For example, compassionate imagery (CI) and ecstasy reduce self-criticism and increase self-compassion to a similar extent, with the effects of CI enhanced in the presence of ecstasy. Here, we examine self-compassion and self-criticism in recreational users who consumed chemically verified MDMA in a within-subjects crossover study. In a naturalistic setting, polydrug-using participants performed a self-focused CI exercise on two occasions separated by ≥6 days: once having consumed self-sourced MDMA and once not. Effects on state self-criticism, self-compassion and emotional empathy were assessed before and after MDMA use (or over an extended baseline period on the occasion that MDMA was not consumed) and reassessed after CI. In participants (n = 20; 8 women) whose ecstasy contained MDMA and no other drug, CI and MDMA appeared to separately increase emotional empathy (to critical facial expressions) and self-compassion. The effects of CI and MDMA on self-compassion also appeared to be additive. Establishing the observed effects in controlled studies will be critical for determining the combined utility of these approaches in fostering adaptive self-attitudes in a therapeutic context.

Kamboj, S. K., Walldén, Y. S., Falconer, C. J., Alotaibi, M. R., Blagbrough, I. S., Husbands, S. M., & Freeman, T. P. (2017). Additive Effects of 3, 4-Methylenedioxymethamphetamine (MDMA) and Compassionate Imagery on Self-Compassion in Recreational Users of Ecstasy. Mindfulness, 1-12. 10.1007/s12671-017-0849-0
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