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MDMA

The re-emergence of hallucinogenic research

February 20, 2018 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / ,

Abstract

Due to the intractability, at times, in the treatment of PTSD, clinicians and researchers continue to explore different options for treatment. This article discusses the renewed interest in hallucinogens for such treatment.
Begola, M. J., & Dowben, J. S. (2018). The re‐emergence of hallucinogenic research. Perspectives in psychiatric care. 10.1111/ppc.12263
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Psychedelics and related drugs: therapeutic possibilities, mechanisms and regulation

February 14, 2018 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

The word “psychedelic” derives from the Greek terms for mind—psyche—and “delos” which means “clear, manifest,” so in essence, psychedelic drugs can be seen as the prototype “window on the mind” concept. The term was originally coined in the 1950s to describe lysergic acid diethylamide (LSD), mescaline, and other hallucinogens, drugs that profoundly alter human experience. These have subsequently been shown to act primarily as agonists at the 5-HT2Areceptor in the brain. Research into the therapeutic potential and mechanisms of action of psychedelic and related drugs peaked in the late 1960s but then stagnated for 50 years after the 1971 UN Psychotropics Convention made psychedelic research with humans almost impossible to carry out (Kyzar et al. 2017).

Recently, however, this area is experiencing a renaissance as drugs often associated with recreational use—such as LSD, ketamine, and cannabis/cannabinoids—have been shown to have therapeutic potential in a range of disorders such as treatment-resistant depression, suicidal ideation, and some pediatric epilepsies. Further, recent pilot studies suggest that MDMA as well as the classic psychedelics, LSD, and psilocybin may contribute to the pharmacopeia for post-traumatic stress disorder (PTSD) and other difficult-to-treat psychiatric disorders. Research has also been stimulated by functional neuroimaging studies of single doses of psychedelics showing that they produce widespread changes in brain connectivity as well as profound alterations to perception and cognition. At the same time, as one would expect from a relatively fledgling area, many questions remain about mechanisms of action, safety, and efficacy. These include what type of psychological therapies best combine with which type of psychedelic drug, whether some types of drug have benefits even without psychological treatment, what the optimal doses are, from single dose through to intermittent or repeated dosing. The current renaissance in empirical psychedelic research stimulated this Special Issue of Psychopharmacology. The articles are grouped into three sections: Clinical efficacy and clinical issues; Effects and Mechanisms of action; Regulation and history.

Curran, H. V., Nutt, D., & de Wit, H. (2018). Psychedelics and related drugs: therapeutic possibilities, mechanisms and regulation. 10.1007/s00213-017-4822-3
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Key interindividual determinants in MDMA pharmacodynamics

February 14, 2018 / MDMA, Papers, Psychology, Publications / 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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Evaluating the abuse potential of psychedelic drugs for medical use in humans

February 7, 2018 / LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Psychology, Publications, Salvia / Salvinorin A, Substance Use Disorder / By / , ,

Abstract

Psychedelics comprise drugs come from various pharmacological classes including 5-HT2A agonists, indirect 5-HT agonists, e.g. MDMA, NMDA antagonists and κ-opioid receptor agonists. There is resurgence in developing psychedelics to treat psychiatric disorders with high unmet clinical need. Many, but not all, psychedelics are schedule 1 controlled drugs (CDs), i.e. no approved medical use. For existing psychedelics in development, regulatory approval will require a move from schedule 1 to a CD schedule for drugs with medical use, i.e. schedules 2-5. Although abuse of the psychedelics is well documented, a systematic preclinical and clinical evaluation of the risks they pose in a medical-use setting does not exist. We describe the non-clinical tests required for a regulatory evaluation of abuse/dependence risks, i.e. drug-discrimination, intravenous self-administration and physical dependence liability. A synopsis of the existing data for the various types of psychedelics is provided and we describe our findings with psychedelic drugs in these models. FDA recently issued its guidance on abuse/dependence evaluation of drug-candidates [59]. We critically review the guidance, discuss the impact this document will have on non-clinical abuse/dependence testing, and offer advice on how non-clinical abuse/dependence experiments can be designed to meet not only the expectations of FDA, but also other regulatory agencies. Finally, we offer views on how these non-clinical tests can be refined to provide more meaningful information to aid the assessment of the risks posed by CNS drug-candidates for abuse and physical dependence.
Heal, D. J., Gosden, J., & Smith, S. L. (2018). Evaluating the abuse potential of psychedelic drugs for medical use in humans. Neuropharmacology. 10.1016/j.neuropharm.2018.01.049
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Taking Psychedelics Seriously

January 22, 2018 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

Background: Psychiatric research in the 1950s and 1960s showed potential for psychedelic medications to markedly alleviate depression and suffering associated with terminal illness. More recent published studies have demonstrated the safety and efficacy of psilocybin, MDMA, and ketamine when administered in a medically supervised and monitored approach. A single or brief series of sessions often results in substantial and sustained improvement among people with treatment-resistant depression and anxiety, including those with serious medical conditions.

Need and Clinical Considerations: Palliative care clinicians occasionally encounter patients with emotional, existential, or spiritual suffering, which persists despite optimal existing treatments. Such suffering may rob people of a sense that life is worth living. Data from Oregon show that most terminally people who obtain prescriptions to intentionally end their lives are motivated by non-physical suffering. This paper overviews the history of this class of drugs and their therapeutic potential. Clinical cautions, adverse reactions, and important steps related to safe administration of psychedelics are presented, emphasizing careful patient screening, preparation, setting and supervision.

Conclusion: Even with an expanding evidence base confirming safety and benefits, political, regulatory, and industry issues impose challenges to the legitimate use of psychedelics. The federal expanded access program and right-to-try laws in multiple states provide precendents for giving terminally ill patients access to medications that have not yet earned FDA approval. Given the prevalence of persistent suffering and growing acceptance of physician-hastened death as a medical response, it is time to revisit the legitimate therapeutic use of psychedelics.

Byock, I. (2018). Taking Psychedelics Seriously. Journal of palliative medicine. 10.1089/jpm.2017.0684
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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, Papers, Psychology, 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, Papers, Psychiatry & Medicine, Psychology, Publications / 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, Psychology, 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 / MDMA, Publications / 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, 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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