MDMA for the treatment of mood disorder: all talk no substance?

Abstract

2007]. This postulate is based on the acute pharmacology of MDMA and is consistent with the hallmark theory of depression, the monoamine hypothesis [Krishnan and Nestler, 2008]. MDMA rapidly increases availability of extracellular 5-hydroxytryptamine (5-HT) at the synapse, mirroring the action of commonly prescribed antidepressants. However, current first-line treatments for depression, such as selective serotonin reuptake inhibitors (SSRIs), typically take about 6 weeks to produce optimum therapeutic change [Frazer and Benmansour, 2002]; MDMA could offer instantaneous relief. This rapid onset is an attractive prospect for treatment-resistant depression (TRD), where currently the only therapeutic option is electroconvulsive therapy (ECT). Although there is a theoretical basis, at present experimental evidence of antidepressant action of MDMA is low, with just one rodent [Majumder et al. 2011] and one volunteer study [Majumder et al. 2012] suggesting direct rapid-onset antidepressant action. MDMA is a controlled substance in most countries, typically in the most restrictive category (Class A in the UK). Despite this, MDMA is already in clinical trials for anxiety disorders such as post-traumatic stress disorder (PTSD), as an adjunct to psychotherapy where it is thought to assist therapy sessions by strengthening the

Psilocybin and MDMA for the treatment of trauma-related psychopathology

“…However, the dosing regimens employed in these studies employed doses over 10 times the average recreational dose used, with multiple dosing sessions sometimes given in rapid succession. This response is unlikely with the lower doses used in modern clinical research (Patel & Titheradge, 2015).…”

“…Mice deficient in the serotonin transporter do not respond to MDMA (Fox et al, 2007) and SSRIs act to attenuate the effects of MDMA, suggesting antagonistic competition to SERT in both animal and human models (Liechti & Vollenweider, 2000;Schmidt & Taylor, 1987). This mechanism suggests MDMA may be a suitable candidate for antidepressant treatment under a similar pharmacological rationale to the therapeutic use of SSRIs (Patel & Titheradge, 2015;White et al, 2008). Post-mortem brain tissue analysis, as well as measurements using cerebrospinal fluid in animal models, have demonstrated 5-HT depletion following acute, MDMA-induced 5-HT release (Schmidt et al, 1986;Taffe et al, 2003).…”

A Review of 3,4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy

“…Other contemporary areas of research with MDMA therapy include the potential for MDMA-assisted psychotherapy in treating mood disorders ( 73 ) and, relatedly, as an alternative to electro-convulsive therapy ( 74 ).…”

Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy

“…Since the mid 2000s, however, there has been a resurgence of interest in MDMA as a medicine to treat various conditions. Considerable research concerning its pharmacological effects and efficacy as a tool in psychotherapy, including several clinical studies in human volunteers, has been conducted recently ( Danforth et al, 2018 ; de la Torre et al, 2004 ; Jerome et al, 2013 ; Parrott, 2007 ; Patel and Titheradge, 2015 ; Sessa et al, 2019 ). At the forefront of this new wave of research is the Multidisciplinary Association for Psychedelic Studies (MAPS), who conducted an early trial with MDMA in humans and published the results in 2011 ( Mithoefer et al, 2011 ), which opened new avenues of research.…”