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MDMA

Combining Cognitive-Behavioral Conjoint Therapy for PTSD with 3,4-Methylenedioxymethamphetamine (MDMA): A Case Example.

March 19, 2019 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

Treatments for posttraumatic stress disorder (PTSD) have evolved significantly in the past 35 years. From what was historically viewed as a pervasive, intractable condition have emerged multiple evidence-based intervention options. These treatments, predominantly cognitive behavioral in orientation, provide significant symptom improvement in 50-60% of recipients. The treatment of PTSD with MDMA-assisted psychotherapy using a supportive, non-directive approach has yielded promising results. It is unknown, however, how different therapeutic modalities could impact or improve outcomes. Therefore, to capitalize on the strengths of both approaches, Cognitive Behavioral Conjoint Therapy for PTSD (CBCT) was combined with MDMA in a small pilot trial. The current article provides a case study of one couple involved in the trial, chosen to provide a demographically representative example of the study participants and a case with a severe trauma history, to offer a detailed account of the methodology and choices made to integrate CBCT and MDMA, as well as an account of their experience through the treatment and their treatment gains. This article offers a description of the combination of CBCT for PTSD and MDMA, and demonstrates that it can produce reductions in PTSD symptoms and improvements in relationship satisfaction.
Wagner, A. C., Mithoefer, M. C., Mithoefer, A. T., & Monson, C. M. (2019). Combining cognitive-behavioral conjoint therapy for PTSD with 3, 4-methylenedioxymethamphetamine (MDMA): A case example. Journal of psychoactive drugs, 51(2), 166-173., https://doi.org/10.1080/02791072.2019.1589028
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Recreational use of psychedelics is associated with elevated personality trait openness: Exploration of associations with brain serotonin markers

February 28, 2019 / MDMA, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

BACKGROUND:

Recent studies have suggested therapeutic benefits of psychedelics for a variety of mental health conditions. The understanding of how single psychedelic administrations can induce long-lasting effects are, in large, still lacking. However, recent studies in both healthy and clinical populations suggest a role for personality changes.

AIM:

To test support for some of these plausible mechanisms we evaluated (cross-sectional) associations between recreational use of psychedelics and 3,4-methylene-dioxymethamphetamine (MDMA) and (a) personality measures and (b) key markers of cerebral serotonergic signalling (serotonin transporter and serotonin-2A-receptor binding).

METHODS:

In 10 psychedelic-preferring recreational users, 14 MDMA-preferring users and 21 non-using controls, personality was assessed using the ‘big five’ instrument Revised NEO Personality Inventory (NEO-PI-R). Frontal serotonin transporter and serotonin-2A-receptor binding potentials were quantified using [11C]DASB and [18F]altanserin positron emission tomography, respectively.

RESULTS:

Of the five NEO-PI-R traits, only openness to experience scores differed between the three groups; psychedelic-preferring recreational users showing higher openness to experience scores when compared with both MDMA-preferring users and controls. Openness to experience scores were positively associated with lifetime number of psychedelic exposures, and among all MDMA-preferring user/psychedelic-preferring recreational user individuals, frontal serotonin transporter binding – but not frontal serotonin-2A-receptor binding – was positively associated with openness to experience.

CONCLUSION:

Our findings from this cross-sectional study support increasing evidence of a positive association between psychedelic experiences and openness to experience, and (a) expands this to the context of ‘recreational’ psychedelics use, and (b) links serotonergic neurotransmission to openness to experience. A modulation of personality induced by psychedelic experiences may have important therapeutic implications via its impact on peoples’ value systems, cognitive flexibility, and individual and social behaviour.

Erritzoe, D., Smith, J., Fisher, P. M., Carhart-Harris, R., Frokjaer, V. G., & Knudsen, G. M. (2019). Recreational use of psychedelics is associated with elevated personality trait openness: Exploration of associations with brain serotonin markers. Journal of Psychopharmacology., 10.1177/0269881119827891
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Greater empathy in MDMA users

February 5, 2019 / MDMA, Papers, Psychology, Publications / By / , , , , ,

Abstract

Background:

3,4-Methylenedioxymethamphetamine (MDMA) is widely known for its positive acute effects on social behaviour, such as increasing empathy, whilst also attenuating the negative impact of social exclusion. However there is a scarcity of research that investigates the long-term impact of recreational MDMA use on these fundamental social processes.

Method:

Sixty-seven individuals were split into three groups based on their drug-use history: poly-drug MDMA users (n = 25), poly-drug users who do not use MDMA (n = 19), alcohol-only users (n = 23), and were tested in an independent groups design. Participants completed both a self-report measure of emotional and cognitive empathy, along with the Multifaceted Empathy Task – a computerised assessment of empathy – and the Cyberball Game – a social exclusion paradigm.

Results:

MDMA users had significantly greater subjective emotional empathy, and greater cognitive empathy on the computer task compared with the poly-drug users who do not use MDMA. There were no significant differences in subjective responses to social exclusion between the groups. Indices of MDMA use did not correlate with empathy.

Conclusions:

Long-term MDMA users in this sample exhibited normal psychosocial functioning in regard to empathy and social pain and had higher subjective emotional empathy. This conflicts with previous suggestions that moderate, long-term MDMA use may cause heightened social distress, and is further evidence of the safety of the drug, which is relevant to considerations of its therapeutic use.
Carlyle, M., Stevens, T., Fawaz, L., Marsh, B., Kosmider, S., & Morgan, C. J. (2019). Greater empathy in MDMA users. Journal of Psychopharmacology, 0269881119826594., 10.1177/0269881119826594
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Perceived Benefits of MDMA-Assisted Psychotherapy beyond Symptom Reduction: Qualitative Follow-Up Study of a Clinical Trial for Individuals with Treatment-Resistant PTSD.

January 7, 2019 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

We present select findings from a long-term follow-up qualitative study of MDMA-assisted psychotherapy for veterans, firefighters, and police officers suffering from chronic, treatment-resistant PTSD. Semi-structured qualitative interviews were conducted at participants’ one-year follow-up after a recently completed phase 2 clinical trial. Available interviews from 19 of 24 participants were analyzed. This qualitative analysis sought to complement, clarify, and expand upon the quantitative findings obtained from the Clinician Administered PTSD Scale (CAPS-IV) and supported by the Long-Term Follow-Up (LTFU) Questionnaire. Pertinent data from interview transcripts were coded and analyzed using an interpretative phenomenological analysis (IPA) methodological framework. We explore prominent thematic elements from participant accounts to better understand the outcomes experienced in this trial. All participants reported experiencing lasting personal benefits and enhanced quality of life that extend beyond quantifiable symptom reduction. We explore a range of treatment benefits beyond symptom reduction to highlight the utility of qualitative investigations of the process and effects of MDMA-assisted psychotherapy. Limitations and challenges encountered in conducting this study are discussed along with recommendations for improved qualitative research protocols in future clinical trials.
Barone, W., Beck, J., Mitsunaga-Whitten, M., & Perl, P. (2019). Perceived Benefits of MDMA-Assisted Psychotherapy beyond Symptom Reduction: Qualitative Follow-Up Study of a Clinical Trial for Individuals with Treatment-Resistant PTSD. Journal of psychoactive drugs, 1-10., https://doi.org/10.1080/02791072.2019.1580805
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Role of serotonin transporter and receptor gene variations in the acute effects of MDMA in healthy subjects

December 27, 2018 / MDMA, Neuroscience, Papers, Publications / By / , ,

Abstract

Methylenedioxymethamphetamine (MDMA; ecstasy) is used recreationally and has been investigated as an adjunct to psychotherapy. Most acute effects of MDMA can be attributed to activation of the serotonin (5-hydroxytryptamine [5-HT]) system. Genetic variants, such as single-nucleotide polymorphisms (SNPs) and polymorphic regions in 5-HT system genes, may contribute to interindividual differences in the acute effects of MDMA. We characterized the effects of common genetic variants within selected genes that encode the 5-HT system (TPH1 [tryptophan 5-hydroxylase 1] rs1800532 and rs1799913, TPH2 [tryptophan 5-hydroxylase 2] rs7305115, HTR1A [5-HT1A receptor] rs6295, HTR1B [5-HT1B receptor] rs6296, HTR2A [5-HT2A receptor] rs6313, and SLC6A4 [serotonin transporter] 5-HTTLPR and rs25531) on the physiological and subjective response to 125 mg MDMA compared with placebo in 124 healthy subjects. Data were pooled from eight randomized, double-blind, placebo-controlled studies that were conducted in the same laboratory. TPH2 rs7305115, HTR2A rs6313, and SLC6A4 5-HTTLPR polymorphisms tended to moderately alter some effects of MDMA. However, after correcting for multiple comparisons, none of the tested genetic polymorphisms significantly influenced the response to MDMA. Variations in genes that encode key targets in the 5-HT system did not significantly influence the effects of MDMA in healthy subjects. Interindividual differences in the 5-HT system may thus play a marginal role when MDMA is used recreationally or therapeutically.

Vizeli, P., Meyer zu Schwabedissen, H. E., & Liechti, M. E. (2018). Role of serotonin transporter and receptor gene variations in the acute effects of MDMA in healthy subjects. ACS chemical neuroscience., 10.1021/acschemneuro.8b00590
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Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions.

December 12, 2018 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / ,

Abstract

BACKGROUND:
For a number of mental health disorders, including posttraumatic stress disorders (PTSD), there are not many available treatment options. Recently, there has been renewed interest in the potential of methylenedioxymethamphetamine (MDMA) to restore function for patients with these disorders. The primary hypothesis is that MDMA, via prosocial effects, increases the ability of patients to address the underlying psychopathology of the disorder. However, the use of MDMA poses potential problems of neurotoxicity, in addition to its own potential for misuse.
METHODS:
In this article, the proposed potential of MDMA as an adjunct to psychotherapy for PTSD is evaluated. The rationale for the use of MDMA and the positive results of studies that have administered MDMA in the treatment of PTSD are provided (pros). A description of potential adverse effects of treatment is also presented (cons). An overview of MDMA pharmacology and pharmacokinetics and a description of potential adverse effects of treatments are also presented. Methylenedioxymethamphetamine-produced oxytocin release and decreased expression of fear conditioning as well as one of the MDMA enantiomers (the n R- entaniomer) are suggested as potential mechanisms for the beneficial effects of MDMA in PTSD (suggestions).
RESULTS:
There is some evidence that MDMA facilitates recovery of PTSD. However, the significant adverse effects of MDMA raise concern for its adoption as a pharmacotherapy. Alternative potential treatments with less adverse effects and that are based on the ubiquitous pharmacology of MDMA are presented.
CONCLUSIONS:
We suggest that additional research investigating the basis for the putative beneficial effects of MDMA might reveal an effective treatment with fewer adverse effects. Suggestions of alternative treatments based on the behavioral pharmacology and toxicology of MDMA and its enantiomers are presented.
Schenk, S., & Newcombe, D. (2018). Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions. Journal of clinical psychopharmacology, 38(6), 632-638., 10.1097/JCP.0000000000000962
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3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats

December 4, 2018 / Anxiety Disorders / PTSD, MDMA, Psychology, Publications / By / , , , , , ,

Abstract

Clinical trials have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) paired with psychotherapy is more effective at reducing symptoms of post-traumatic stress disorder(PTSD) than psychotherapy or pharmacotherapy, alone or in combination. The processes through which MDMA acts to enhance psychotherapy are not well understood. Given that fear memories contribute to PTSD symptomology, MDMA could augment psychotherapy by targeting fear memories. The current studies investigated the effects of a single administration of MDMA on extinction and reconsolidation of cued and contextual fear memory in adult, male Long-Evans rats. Rats were exposed to contextual or auditory fear conditioning followed by systemic administration of saline or varying doses of MDMA (between 1 and 10 mg/kg) either 30 min before fear extinction training or immediately after brief fear memory retrieval (i.e. during the reconsolidation phase). MDMA administered prior to fear extinction training failed to enhance fear extinction memory, and in fact impaired drug-free cued fear extinction recall without impacting later fear relapse. MDMA administered during the reconsolidation phase, but not outside of the reconsolidation phase, produced a delayed and persistent reduction in conditioned fear. These findings are consistent with a general memory-disrupting effect of MDMA and suggest that MDMA could augment psychotherapy by modifying fear memories during reconsolidation without necessarily enhancing their extinction.

Hake, H. S., Davis, J. K., Wood, R. R., Tanner, M. K., Loetz, E. C., Sanchez, A., … & Greenwood, B. N. (2019). 3, 4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats. Physiology & behavior, 199, 343-350., 10.1016/j.physbeh.2018.12.007
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Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions.

December 1, 2018 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / ,

Abstract

BACKGROUND:
For a number of mental health disorders, including posttraumatic stress disorders (PTSD), there are not many available treatment options. Recently, there has been renewed interest in the potential of methylenedioxymethamphetamine (MDMA) to restore function for patients with these disorders. The primary hypothesis is that MDMA, via prosocial effects, increases the ability of patients to address the underlying psychopathology of the disorder. However, the use of MDMA poses potential problems of neurotoxicity, in addition to its own potential for misuse.
METHODS:
In this article, the proposed potential of MDMA as an adjunct to psychotherapy for PTSD is evaluated. The rationale for the use of MDMA and the positive results of studies that have administered MDMA in the treatment of PTSD are provided (pros). A description of potential adverse effects of treatment is also presented (cons). An overview of MDMA pharmacology and pharmacokinetics and a description of potential adverse effects of treatments are also presented. Methylenedioxymethamphetamine-produced oxytocin release and decreased expression of fear conditioning as well as one of the MDMA enantiomers (the n R- entaniomer) are suggested as potential mechanisms for the beneficial effects of MDMA in PTSD (suggestions).
RESULTS:
There is some evidence that MDMA facilitates recovery of PTSD. However, the significant adverse effects of MDMA raise concern for its adoption as a pharmacotherapy. Alternative potential treatments with less adverse effects and that are based on the ubiquitous pharmacology of MDMA are presented.
CONCLUSIONS:
We suggest that additional research investigating the basis for the putative beneficial effects of MDMA might reveal an effective treatment with fewer adverse effects. Suggestions of alternative treatments based on the behavioral pharmacology and toxicology of MDMA and its enantiomers are presented.
Schenk, S., & Newcombe, D. (2018). Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions. Journal of clinical psychopharmacology, 38(6), 632-638., 10.1097/JCP.0000000000000962
Link to full text

Neuroimaging of chronic MDMA (“ecstasy”) effects: A meta-analysis

November 12, 2018 / MDMA, Neuroscience, Papers, Publications / By / , , ,

Abstract

In this meta-analysis, we aimed to assess the evidence from neuroimaging studies for chronic alterations in the brains of MDMA users. The databases PubMed, Embase, and Web of Science were searched for studies published from inception to August 24, 2018, without any language restriction. Sixteen independent studies comprising 356 MDMA users and 311 controls were included. Of these, five studies investigated frontal and occipital N-acetylaspartate/creatine and myo-inositol/creatine ratios, three studies assessed basal ganglia blood flow and ten studies investigated serotonin transporter (SERT) density in various regions. We found significantly decreased SERT density in eight of 13 investigated regions. Meta-regression indicated a positive association with abstinence, but none with lifetime episodes of use. Therefore, other variables (such as doses taken per occasion) might be more important determinants. Positive associations between time of abstinence and SERT density might indicate that these alterations are reversible to some extent. Furthermore, there were no significant differences between user and control groups in terms of neurochemical ratios in the frontal and occipital lobes and blood flow in the basal ganglia. Overall, MDMA user groups showed heavy use patterns and study quality was poor.

Müller, F., Brändle, R., Liechti, M. E., & Borgwardt, S. (2018). Neuroimaging of chronic MDMA (“ecstasy”) effects: A meta-analysis of the literature. Neuroscience & Biobehavioral Reviews., 10.1016/j.neubiorev.2018.11.004
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