Wagner, M., Mithoefer, M., Mithoefer, A., MacAulay, R., Jerome, L., Bazaar-Klosinski, B., & Doblin, R. (2016). B-56Investigation of Personality Change Following MDMA-Assisted Psychotherapy for Post Traumatic Stress Disorder. Archives of Clinical Neuropsychology, 31(6), 634-634. 10.1093/arclin/acw043.131
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MDMA, better known as the recreational drug “ecstasy,” is well known for stimulating a feeling of closeness and empathy in its users. We advocate that exploring its mechanism of action could lead to new treatments for psychiatric conditions characterized by impairments in social behavior.
Heifets, B. D., & Malenka, R. C. (2016). MDMA as a Probe and Treatment for Social Behaviors. Cell, 166(2), 269-272. http://dx.doi.org/10.1016/j.cell.2016.06.045
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There is a range of therapies to treat Post Traumatic Stress Disorder (PTSD) but treatment resistance remains high, with many sufferers experiencing the chronic condition. Engagement in trauma-focused psychotherapy is difficult for some patients with PTSD, especially those with extreme affect dysregulation associated with recall of traumatic memories. In recent years there have been a number of neuroscientific and clinical studies examining the potential role for adjunctive drug-assisted psychotherapy using 3,4,-methylenedioxmethamphetamine (MDMA) as a treatment for PTSD. re-visiting of a novel approach to trauma-focused psychotherapy with Used just two or three times, under careful medical supervision and specialised psychotherapy support MDMA appears to facilitate the recall of traumatic memories without the user feeling overwhelmed by the negative affect that usually accompanies such memories. This therapeutic approach began in the 1980s and was subsequently shelved in the midst of public health concerns surrounding the recreational use of the drug ecstasy. When pharmaceutical grade MDMA is used in a clinical setting it does not share the same risk profiles as ecstasy. Recent phase one neurophysiological studies and phase two clinical studies are showing promise as a potential new approach to managing treatment-resistant PTSD.
Sessa, B. (2016). MDMA and PTSD Treatment. Neuroscience Letters. http://dx.doi.org/10.1016/j.neulet.2016.07.004
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Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse. This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the molecular to the behavioral level, and presenting the most up-to-date information on clinically oriented research with these substances, with important ramifications for their potential therapeutic value.
Garcia-Romeu, A., Kersgaard, B., & Addy, P. H. (2016). Clinical applications of hallucinogens: A review. Experimental and clinical psychopharmacology, 24(4), 229. 10.1037/pha0000084
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Rationale: The synthetic phenethylamines are recreational drugs known to produce psychostimulant effects. However, their abuse potential has not been widely studied.
Objectives: Here, we investigated the rewarding and the hallucinatory effects of 2,5-dimetoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA) in comparison with the classical 3,4-methylenedioxymethamphetamine (MDMA). In addition, the role of serotonin 5-HT2-like receptor on the abovementioned effects was evaluated.
Methods: Zebrafish were intramuscularly (i.m.) treated with a wide range of doses of DOB (0.1–20 mg/kg), PMA (0.0005–2 mg/kg), or MDMA (0.5–160 mg/kg). Animals were submitted to a conditioned place preference (CPP) task, to investigation of the rewarding properties, and to the evaluation of hallucinatory behavior in terms of appearance of a trance-like behavior. The serotonin 5-HT2 subtype receptor antagonist ritanserin (0.025–2.5 mg/kg) in association with the maximal effective dose of MDMA, DOB, and PMA was given i.m., and the effect on CPP or hallucinatory behavior was evaluated.
Results: MDMA and its derivatives exhibited CPP in a biphasic fashion, being PMA the most potent. This effect was accompanied, for DOB (2 mg/kg) and PMA (0.1 mg/kg), by a trance-like hallucinatory behavior. MDMA at a high dose as 160 mg/kg did not induce any hallucinatory behavior. Ritanserin significantly blocked the rewarding and hallucinatory effects suggesting the involvement of serotonin 5HT2 subtype receptor.
Conclusion: Collectively, these findings demonstrate for the first time that the rewarding properties of DOB and PMA are accompanied by hallucinatory behavior through a serotonergic system and reinforce zebrafish as an emerging experimental model for screening new hallucinogens.
Ponzoni, L., Daniela, B., & Sala, M. (2016). Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: role of serotonin 5HT2-type receptors. Psychopharmacology, 1-9. http://dx.doi.org/10.1007/s00213-016-4352-4
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Background: National surveys suggest ecstasy (3,4-methylenedioxymethamphetamine [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][MDMA]) use has decreased substantially among adolescents in the US since 2001; however, the recent phenomenon of “Molly” (ecstasy marketed as “pure MDMA”) may be leading to underreporting of use as not all users are aware that “Molly” is a form of ecstasy.
Methods: We examined 2014 data from Monitoring the Future, a nationally representative survey of high school seniors in the US (N = 6250, modal age: 18). Three randomly distributed survey forms asked about ecstasy use, and one included “Molly” in the definition. Self-reported lifetime, 12-month, and 30-day ecstasy use were compared to determine whether including “Molly” in the definition was associated with higher prevalence or frequency of use.
Results: The form including “Molly” in the definition had significantly higher prevalence than the two (combined) forms that did not. Lifetime use (8.0% vs. 5.5%) and 12-month use (5.1% vs. 3.6%) were significantly higher with “Molly” in the definition. Lifetime prevalence remained higher with “Molly” in the definition when controlling for correlates of ecstasy use; however, 12-month use did not. Differences in prevalence were associated with lifetime occasions of use, with lower concordance between forms at lower levels of lifetime occasions (e.g., 1–2 times). Survey form was not related to number of times used among more frequent users.
Conclusions: Prevalence of ecstasy use appears to be underestimated when “Molly” is not included in the definition of ecstasy/MDMA. Surveys should include “Molly” in the definition of ecstasy to more adequately assess prevalence of use.
Palamar, J. J., Keyes, K., & Cleland, C. M. (2016). Underreporting of ecstasy use among high school seniors in the US. Drug and Alcohol Dependence. http://dx.doi.org/10.1016/j.drugalcdep.2016.06.001
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Acute exposure to ±3,4-methylenedioxymethamphetamine (MDMA) preferentially increases release of serotonin (5-HT), and a role of 5-HT in many of the behavioral effects of acute exposure to MDMA has been demonstrated. A role of 5-HT in MDMA self-administration in rats has not, however, been adequately determined. Therefore, the present study measured the effect of pharmacological manipulation of some 5-HT receptor subtypes on self-administration of MDMA. Rats received extensive experience with self-administered MDMA prior to tests with 5-HT ligands. Doses of the 5-HT1A antagonist, WAY 100635 (0.1-1.0mg/kg), 5-HT1B antagonist, GR 127935 (1.0-3.0mg/kg), and the 5-HT2A antagonist, ketanserin (1.0-3.0mg/kg) that have previously been shown to decrease self-administration of other psychostimulants and that decreased MDMA-produced hyperactivity in the present study did not alter MDMA self-administration. Experimenter-administered injections of MDMA (10.0mg/kg, ip) reinstated extinguished drug-taking behavior, but this also was not decreased by any of the antagonists. In contrast, both WAY 100635 and ketanserin, but not GR 127935, decreased cocaine-produced drug seeking in rats that had been trained to self-administered cocaine. The 5-HT1A agonist, 8-OH-DPAT (0.1-1.0mg/kg), but not the 5-HT1B/1A agonist, RU 24969 (0.3-3.0mg/kg), decreased drug-seeking produced by the reintroduction of a light stimulus that had been paired with self-administered MDMA infusions. These findings suggest a limited role of activation of 5-HT1A, 5-HT1B or 5-HT2 receptor mechanisms in MDMA self-administration or in MDMA-produced drug-seeking following extinction. The data suggest, however, that 5-HT1A agonists inhibit cue-induced drug-seeking following extinction of MDMA self-administration and might, therefore, be useful adjuncts to therapies to limit relapse to MDMA use.
Schenk, S., Foote, J., Aronsen, D., Bukholt, N., Highgate, Q., Van de Wetering, R., & Webster, J. (2016). Serotonin antagonists fail to alter MDMA self-administration in rats. Pharmacology Biochemistry and Behavior. http://dx.doi.org/10.1016/j.pbb.2016.06.002
This prospective study was designed to test whether the variables proposed by the Theory of Planned Behavior (TPB) were associated with baseline intention to implement and subsequent use of 2 MDMA/ecstasy-specific harm reduction interventions: preloading/postloading and pill testing/pill checking. Using targeted Facebook advertisements, an international sample of 391 recreational ecstasy users were recruited to complete questionnaires assessing their ecstasy consumption history, and their attitudes, subjective norms, perceived behavioral control, habit strength (past strategy use), and intention to use these two strategies. Attitudes, subjective norms, and perceived behavioral control were significantly associated with baseline intention to preload/postload and pill test/pill check. Out of the 391 baseline participants, 100 completed the two-month follow-up assessment. Baseline habit strength and frequency of ecstasy consumption during the three months prior to baseline were the only significant predictors of how often participants used the preloading/postloading strategy during the follow-up. Baseline intention to pill test/pill check was the only significant predictor of how often participants used this strategy during the follow-up. These findings provide partial support for TPB variables as both correlates of baseline intention to implement and predictors of subsequent use of these two strategies. Future investigations could assess whether factors related to ecstasy consumption (e.g., subjective level of intoxication, craving, negative consequences following consumption), and environmental factors (e.g., accessibility and availability of harm reduction resources) improve the prediction of how often ecstasy users employ these and other harm reduction strategies.
Davis, A. K., & Rosenberg, H. (2016). Using the Theory of Planned Behavior to predict implementation of harm reduction strategies among MDMA/ecstasy users. Psychology of Addictive Behaviors, 30(4), 500. http://dx.doi.org/10.1037/adb0000167
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Post-traumatic stress disorder (PTSD) is a serious condition that afflicts millions of individuals in the United States. Its complexity has resulted in physicians struggling to effectively implement and maintain treatment. Emerging studies suggest that ±3,4-Methylenedioxymethamphetamine (MDMA), or “ecstasy”, may prove beneficial in treating PTSD in combination with conventional psychotherapy. By acting on the 5-HT transporter in the brain, MDMA has been found to have positive effects on brain activity; encouraging neuroplasticity through the accumulation of brain-derived neurotrophic factor (BDNF). Integrating psychoactive drugs into polytrauma therapy will broaden our understanding of the components involved in maintaining wellness in the human psyche.
Baxter, A. (2016). ±3, 4-Methylenedioxymethamphetamine: Treating PTSD in The Modern World.
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Since the wars in Iraq and Afghanistan, posttraumatic stress disorder (PTSD) has become a major area of research and development. The most widely accepted treatment for PTSD is prolonged exposure (PE) therapy, but for many patients it is intolerable or ineffective. ±3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AP) has recently re-emerged as a new treatment option, with two clinical trials having been published and both producing promising results. However, these results have yet to be compared to existing treatments. The present paper seeks to bridge this gap in the literature. Often the statistical significance of clinical trials is overemphasized, while the magnitude of the treatment effects is overlooked. The current meta-analysis aims to provide a comparison of the cumulative effect size of the MDMA-AP studies with those of PE. Effect sizes were calculated for primary and secondary outcome measures in the MDMA-AP clinical trials and compared to those of a meta-analysis including several PE clinical trials. It was found that MDMA-AP had larger effect sizes in both clinician-observed outcomes than PE did (Hedges’ g=1.17 vs. g=1.08, respectively) and patient self-report outcomes (Hedges’ g=0.87 vs. g=0.77, respectively). The dropout rates of PE and MDMA-AP were also compared, revealing that MDMA-AP had a considerably lower percentage of patients dropping out than PE did. These results suggest that MDMA-AP offers a promising treatment for PTSD.
Amoroso, T., & Workman, M. (2016). Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy. Journal of psychopharmacology (Oxford, England). http://dx.doi.org/10.1177/0269881116642542
