Use of MDMA in the treatment of Post-traumatic Stress Disorder

Treballs Finals de Grau de Farmàcia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, 2018. Tutor: David Pubill.[eng] 3,4-methylenedioxy-N-methylamphetamine (MDMA; also known as "ecstasy") is a psychoactive drug that was first synthesized in 1912 by the pharmaceutical company Merck. This amphetamine derivative has been investigated for clinical purposes as it has various interesting mood-altering properties, although in the 1980s was Schedule-I controlled in the United Kingdom, which implies a non-approved medical use, potential for high abuse and illegallity in terms of possession. Since MDMA was banned, there has been a campaign to mantain interest in the potential therapeutic value of MDMA, including post-traumatic stress disorder (PTSD). PTSD is a prevalent and disabling disorder, frequently chronic and associated with significant morbidity, poor quality of life, and high personal, social and economic costs. For many patients, the traumatic memories are so powerful and distressing that they cannot bare the emotions subsequent to their recovery, and therefore find themselves unable to complete the therapy. MDMA has the ability to reduce the brain responses to threats, which may allow patients to engage fully in the treatment. This work analyzes the latest reports about this treatment and also revise evidence from randomized controlled trials (RCTs) for the efficacy of acute and long-term pharmacotherapy for PTSD, including the treatment of refractory PTSD with MDMA. Keywords: MDMA, MDMA psychotherapy, PTSD, post-traumatic stress disorder[cat] La 3,4-metilendioxi-N-metilamfetamina (MDMA; també coneguda com èxtasi) és una molècula psicoactiva que va ser sintetitzada per l'empresa farmacèutica Merck l'any 1912. Aquest derivat amfetamínic s'ha investigat amb objectius clínics degut a les seves propietats interessants d'alteració de l'estat d'ànim. Als anys 80 va ser categoritzat al Regne Unit com a substància de categoria 1, "Schedule I", i en conseqüència va definir-se com a substància sense ús mèdic aprovat, amb potencial d'abús alt i de possessió il·legal. Des que es va prohibir, hi ha hagut una campanya per mantenir interès en el seu potencial terapèutic, incloent el tractament del trastorn d'estrès post-traumàtic (TEPT). El TEPT és un trastorn prevalent i inhabilitant, freqüentment crònic i associat a una elevada morbiditat, qualitat baixa de vida i costs elevats personals, socials i econòmics. Per molts pacients, les memòries de la situació traumàtica que ha desencadenat en la malaltia són tan fortes i desagradables que no poden tolerar les emocions resultants de la recuperació, i per tant no poden completar la teràpia. L'MDMA té l'habilitat de reduïr les respostes neuronals a aquestes amenaces, fent que els pacients puguin afrontar el tractament de forma completa. Aquest treball analitza les últimes informacions sobre aquest tractament i també revisa l'evidència d'assajos clínics randomitzats per l'eficàcia de la farmacoteràpia a llarg plaç per el TEPT, incloent el tractament de TEPT refractari amb MDMA. Paraules clau: MDMA, psicoteràpia amb MDMA, TEPT, trastorn d'estrès post-traumàti

Quadratic differential systems with a weak focus of first order and a finite saddle-node

Planar quadratic differential systems occur in many areas of applied mathematics. Although more than one thousand papers were written on these systems, a complete understanding of this class is still missing. Classical problems, and in particular, Hilbert’s 16th problem, are still open for this class. One of the goals of recent researchers is the topological classification of quadratic systems. As this attempt is not possible in the whole class due to the large number of parameters, many subclasses are considered and studied in a methodical way to get the objective. The purpose of this Master’s thesis is to contribute to the previous research project by performing a global study of the class defined as the closure within real quadratic differential systems of the family Qwf1sn consisting of all quadratic systems possessing a weak focus of first order and a finite saddle-node. To do so, some recent techniques in qualitative theory will be used, as for example the theory of algebraic invariants and comitants developed by the Sibirsky’s School

A polarizable ion model for the structure of molten AgI

The results are reported of the molecular dynamics simulations of the coherent static structure factor of molten AgI at 923 K using a polarizable ion model. This model is based on a rigid ion potential, to which the many body interactions due to the anions induced polarization are added. The calculated structure factor is in better agreement with recent neutron diffraction data than that obtained by using simple rigid ion pair potentials. The Voronoi-Delaunay method has been applied to study the relationship between voids in the spatial distribution of cations and the prepeak of the structure factor.Comment: 12 pages, 4 figure

Els gabinets de premsa com a mediadors entre els científics i els mitjans

L'impacte diari de la ciència en la societat actual fa necessari, cada vegada més, un coneixement públic de la ciència. La percepció que la societat té dels investigadors i dels descobriments científics depèn sobretot de com es comunica la ciència, qui ho comunica i per què. L'article segueix el flux de la notícia científica des dels seus creadors, els científics, fins a la interacció d'aquests amb els mitjans de comunicació, i se centra específicament en el paper que els gabinets de premsa tenen com a mediadors i difusors de la informació.Science’s ever growing impact on today’s society imposes a public understanding of science. Society’s perception of scientists and science breakthroughs depend mainly on the way science is communicated, who communicates it and their intention underneath it. The article follows the path of science news, from the source-scientists-their interaction with the media, concentrating specifically on the role of Press Departments as mediators between scientist sources and journalists

Mass and size dependence of single ion dynamics in molten monohalides

This work is concerned with four molten monohalides with different ionic radii ratios (RbCl, NaI, AgCl, and CuCl) and ideal isotopic systems of these salts with different ionic mass ratios. The velocity autocorrelation functions of the two ionic species in each melt have been studied by both a theoretical approximation and molecular dynamics simulations. It is found that their main features may be qualitatively predicted by considering suitable combinations of the second and fourth frequency moments of their spectra. The analysis of these two parameters allows us to determine how the structure (strongly dependent on the ionic size difference) and the ionic masses contribute to the shape of the velocity autocorrelation functions. The results show that the averaged microscopic motion of the small ions is mainly determined by the first neighboring shell of unlike ions, whereas the nearest shell of like ions also affects the dynamics of the large ions. This effect is more pronounced as the size difference is greater. Furthermore, it is concluded that the size differences encourage the rattling motion of the large ions, whereas the mass difference encourages the backscattering and oscillations of the velocity autocorrelation function of the light ions. A simple rule is derived to determine the interplay between these two effects. Comparison between the mass and nearest distance ratios enables the prediction as to which species will experience a more pronounced backscatteringmotion. The size difference effects prevail in the hydrodynamics regime and the self-diffusion coefficient of the small ions is higher than that of the large ones. The difference between the self-diffusion coefficient increases as the size differences increases.Postprint (published version

Br diffusion in molten NaBr explored by coherent quasielastic neutron scattering

Molten sodium bromide has been investigated by quasielastic neutron scattering focusing on the wave vector range around the first structure factor peak. The linewidth of the scattering function shows a narrowing around the wave number of the structure factor peak, known as deGennes narrowing. In a monatomic system, this narrowing or in the time domain slowing down, has been related to a self-diffusion process of the caged particle. Here we show that this methodology can be applied to the molten alkali halide NaBr. The incoherent scattering from the sodium ions at small wave vectors provides the self-diffusion coefficient of sodium and the dynamics of bromine ions can be studied at wave numbers around the structure factor peak. With input from molecular dynamics simulations on the partial structure factors, diffusion coefficients of the bromine ions can be obtained. These experimentally derived diffusion coefficients are in good agreement with molecular dynamics simulation results. This methodology to extract self-diffusion coefficients from coherent quasielastic neutron scattering is applicable to binary fluids in general when one particle dominates the scattering response at the structure factor maximum.Postprint (author's final draft