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MDMA

Potential Psychiatric Uses for MDMA

Abstract

Phase 2 trials of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy have demonstrated initial safety and efficacy for treatment of PTSD, with potential for expansion to depression and anxiety disorders. In these trials, single doses of MDMA are administered in a model of medication-assisted psychotherapy, differing from trials involving daily drug administration without psychotherapy. This model presents an opportunity to utilize accelerated regulatory pathways, such as FDA Breakthrough Therapy Designation, to most effectively and expeditiously test such novel approaches.

Klosinski, B. B., & Mithoefer, M. C. (2016). Potential Psychiatric Uses for MDMA. Clinical Pharmacology & Therapeutics. 10.1002/cpt.565
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Psychological effects of MDMA

Abstract

Zinberg’s Interaction Model implies that the content of a drug-induced experience is a function of the pharmacological properties of the drug, the set (the user’s characteristics e.g. motivation and personality), and the setting (the physical and social context). The current research investigated the function of the set and setting and their role in shaping the psychological effects of 3,4-methylenedioxmethamphetamine (MDMA), as well as their role in reducing the risk of drug abuse.
An online survey was distributed among adult MDMA polydrug users (n = 158) and MDMA-naïve controls (alcohol, nicotine and cannabis users, n = 138). Participants answered questions regarding their pattern of drug use, their motivation for MDMA use and the setting (e.g. clubbing, home with friends), as well as the subjective effects of MDMA. Participants also completed a range of self-report measures of self-reflection and insight, emotional intelligence, and personality, as well as a drug dependency measure.
MDMA users displayed higher levels of self-reflection and insight, openness to new experience and lower levels of neuroticism and conscientiousness, in comparison to the control group. The significant predictors of self-reflection and insight were openness, emotional intelligence, MDMA use, extraversion and neuroticism. When the analysis was rerun only for the MDMA group, the significant predictors of self-reflection and insight were openness, emotional intelligence and self-insight effects of MDMA. High levels of self-reported negative effects of MDMA were predictors of a problematic drug use.
These findings suggest that there might be a relationship between MDMA use and higher levels of self-reflection and insight; however, longitudinal studies are required to further investigate the causality of this relationship. The results add to existing evidence that MDMA has potential for altering emotional experiences. Further research utilising a prospective design is warranted.

Wieliczko, M. J. (2016). Psychological effects of MDMA (Doctoral dissertation, Canterbury Christ Church University).

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The Relationship between depression and use of ecstasy among adolescents in Taiwan

Abstract

Introduction: The aim of this cross-sectional study was to examine the relationship between depression and ecstasy use among adolescents in Taiwan by controlling for the effects of demographic characteristics and cannabis use.

Methods: A total of 10,262 adolescents aged 12-18 years completed research questionnaires that assessed their severity of depression, status of ecstasy use, and history of cannabis use. The participants were grouped into non-users, ex-users, and current users. Severity of depression among these three adolescent groups was compared using analysis of covariance (ANCOVA), considering the history of cannabis use and demographic characteristics as covariates.
Results: After controlling for history of cannabis use and age, the study found that current ecstasy users experienced more severe depressive symptoms than ex-users and non-users. The difference between ex-users and non-users was not significant.
Conclusion: This study found that current ecstasy users had more severe depressive symptoms than non-users and ex-users. Psychological health professionals must monitor depressive symptoms among adolescent ecstasy users and provide emotional regulation strategies and psychological intervention for those with significant depression.
Lee, K. H., Su, C. H., Hsiao, R. C., Yen, C. N., & Yen, C. F. (2016). The Relationship between depression and use of ecstasy among adolescents in Taiwan. Neuropsychiatry (London), 6(4), 124-127. 10.4172/Neuropsychiatry.1000130
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Psychedelic Psychotherapy Insights From 25 Years of Research

Abstract

Presented at a conference titled “Psychedelic Science 2013,” highlighting the resumption of investigations with psychedelic substances (i.e., psilocybin, DMT, LSD, MDMA, etc.) in the United States and Europe after a dormant period of more than two decades, the author presents insights and perspectives gleaned from his 25 years of clinical research experience. After acknowledging the vastness and potential significance of this research frontier, the article focuses on the “cartography of inner space”; the unique therapeutic potential of transcendental states of consciousness; the entelechy of the interpersonally grounded psyche; the importance of integration in drug-free therapy sessions; the roles of expectation, religious education and faith; the role of music; and future research directions.

Richards, W. A. (2016). Psychedelic Psychotherapy Insights From 25 Years of Research. Journal of Humanistic Psychology, 0022167816670996.
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A Case of 3,4-Dimethoxyamphetamine (3,4-DMA) and 3,4 Methylendioxymethamphetamine (MDMA) Toxicity with Possible Metabolic Interaction

Abstract

BACKGROUND: We present a case of “ecstasy” ingestion revealing 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-dimethoxyamphetamine (3,4-DMA) and absence of cytochrome P450 (CYP)-2D6 MDMA metabolites.

CASE REPORT: A 19-year-old presented following a seizure. Initial vital signs were normal. Laboratories were normal with the exception of sodium 127 mEq/L and urine drugs of abuse screen positive for amphetamines. Twelve hours later, serum sodium was 114 mEq/L and a second seizure occurred. After receiving hypertonic saline (3%), the patient had improvement in mental status and admitted to taking “ecstasy” at a rave prior to her initial presentation. Liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS) of serum and urine revealed MDMA, 3,4-DMA, and the CYP-2B6 MDMA metabolites 3,4-methylendioxyamphetamine (MDA) and 4-hydroxy-3-methoxyamphetamine (HMA). The CYP2D6 metabolites of MDMA, 3,4-dihydromethamphetamine (HHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), were detected at very low levels.

CONCLUSION: This case highlights the polypharmacy which may exist among users of psychoactive illicit substances and demonstrates that concurrent use of MDMA and 3,4-DMA may predispose patients to severe toxicity. Toxicologists and other healthcare providers should be aware of this potential toxicity.

Darracq, M. A., Thornton, S. L., Minns, A. B., & Gerona, R. R. (2016). A Case of 3, 4-Dimethoxyamphetamine (3, 4-DMA) and 3, 4 Methylendioxymethamphetamine (MDMA) Toxicity with Possible Metabolic Interaction. Journal of Psychoactive Drugs, 1-4. 10.1080/02791072.2016.1225324
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The effects of ecstasy on neurotransmitter systems: a review on the findings of molecular imaging studies

Abstract

Rationale: Ecstasy is a commonly used psychoactive drug with 3,4-methylenedioxymethamphetamine (MDMA) as the main content. Importantly, it has been suggested that use of MDMA may be neurotoxic particularly for serotonergic (5-hydroxytryptamine (5-HT)) neurons. In the past decades, several molecular imaging studies examined directly in vivo the effects of ecstasy/MDMA on neurotransmitter systems.

Objectives: The objective of the present study is to review the effects of ecstasy/MDMA on neurotransmitter systems as assessed by molecular imaging studies in small animals, non-human primates and humans.

Methods: A search in PubMed was performed. Eighty-eight articles were found on which inclusion and exclusion criteria were applied.

Results: Thirty-three studies met the inclusion criteria; all were focused on the 5-HT or dopamine (DA) system. Importantly, 9 out of 11 of the animal studies that examined the effects of MDMA on 5-HT transporter (SERT) availability showed a significant loss of binding potential. In human studies, this was the case for 14 out of 16 studies, particularly in heavy users. In abstinent users, significant recovery of SERT binding was found over time. Most imaging studies in humans that focused on the DA system did not find any significant effect of ecstasy/MDMA use.

Conclusions: Preclinical and clinical molecular imaging studies on the effects of ecstasy/MDMA use/administration on neurotransmitter systems show quite consistent alterations of the 5-HT system. Particularly, in human studies, loss of SERT binding was observed in heavy ecstasy users, which might reflect 5-HT neurotoxicity, although alternative explanations (e.g. down-regulation of the SERT) cannot be excluded.

Vegting, Y., Reneman, L., & Booij, J. (2016). The effects of ecstasy on neurotransmitter systems: a review on the findings of molecular imaging studies. Psychopharmacology, 1-29. 10.1007/s00213-016-4396-5

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The effects of MDMA on socio-emotional processing: Does MDMA differ from other stimulants?

Abstract

±3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that enhances sociability and feelings of closeness with others. These “prosocial” effects appear to motivate the recreational use of MDMA and may also form the basis of its potential as an adjunct to psychotherapy. However, the extent to which MDMA differs from prototypic stimulant drugs, such as dextroamphetamine, methamphetamine, and methylphenidate, in either its behavioral effects or mechanisms of action, is not fully known. The purpose of this review is to evaluate human laboratory findings of the social effects of MDMA compared to other stimulants, ranging from simple subjective ratings of sociability to more complex elements of social processing and behavior. We also review the neurochemical mechanisms by which these drugs may impact sociability. Together, the findings reviewed here lay the groundwork for better understanding the socially enhancing effects of MDMA that distinguish it from other stimulant drugs, especially as these effects relate to the reinforcing and potentially therapeutic effects of the drug.

Bershad, A. K., Miller, M. A., Baggott, M. J., & de Wit, H. (2016). The effects of MDMA on socio-emotional processing: Does MDMA differ from other stimulants?. Journal of Psychopharmacology, 0269881116663120.
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Urinary and plasma oxytocin changes in response to MDMA or intranasal oxytocin administration

Abstract

BACKGROUND:
The neuropeptide oxytocin (OT) has received increased experimental attention for its putative role in both normal social functioning and several psychiatric disorders that are partially characterized by social dysfunction (e.g., autism spectrum disorders: ASD). Many human experimental studies measure circulating plasma levels of OT in order to examine the relationship between the hormone and behavior. Urinary OT (uOT) assays offer a simple, easy, and non-invasive method to measure peripheral hormone levels, but the correspondence between uOT and plasma OT (pOT) levels is unclear. Here, we conducted two within-subjects, double-blind studies exploring changes in uOT and pOT levels following administration of two drugs: MDMA, an oxytocin-releasing drug (Study 1), and intranasal oxytocin (INOT: Study 1 and 2).
METHODS:
In Study 1, 14 adult participants (2 females) were each administered either oral 1.5mg/kg MDMA or 40IU INOT across two different study sessions. In Study 2, 10 male participants (adolescents and young adults) diagnosed with ASD received either 40IU INOT or placebo across two different sessions. In both studies, blood and urine samples were collected before and after drug administration at each study session. For Study 1, 10 participants provided valid plasma and urine samples for the MDMA session, and 8 provided valid samples for the INOT session. For Study 2, all 10 participants provided valid samples for both INOT and placebo sessions. Pre- and post-administration levels of pOT and uOT were compared. Additionally, correlations between percent change from baseline uOT and pOT levels were examined.
RESULTS:
Study 1: Plasma OT and uOT levels significantly increased after administration of MDMA and INOT. Furthermore, uOT levels were positively correlated with pOT levels following administration of MDMA (r=0.57, p=0.042) but not INOT (r=0.51, p=0.097). Study 2: There was a significant increase in uOT levels after administration of INOT, but not after administration of placebo. Under both conditions, INOT and placebo, significant increases in pOT levels were not observed. Additionally, change from baseline uOT and pOT levels were positively correlated (r=0.57, p=0.021). There was no significant correlation between uOT and pOT levels following placebo administration.
CONCLUSION:
Our results show a measurable and significant increase in pOT and uOT levels after the administration of MDMA (Study 1) and INOT (Study 1 and Study 2). Additionally, a positive correlation between uOT and pOT levels was observed in both samples (healthy adults and ASD patients) in at least one condition. However, uOT and pOT levels were not correlated under all conditions, suggesting that uOT levels do not fully correspond to pOT levels in the time windows we measured. Future studies should further examine the relationship between levels of pOT and uOT in healthy and clinical populations on measures of social behavior because uOT may serve as an additional non-invasive method to measure peripheral OT changes.
Francis, S. M., Kirkpatrick, M. G., de Wit, H., & Jacob, S. (2016). Urinary and plasma oxytocin changes in response to MDMA or intranasal oxytocin administration. Psychoneuroendocrinology74, 92-100. 10.1016/j.psyneuen.2016.08.011
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