OPEN Foundation

Day: 1 July 2020

The Effects of 3,4-methylenedioxymethamphetamine on Neurogenesis in the Hippocampus of Male Rats

Abstract

Introduction: The administration of 3,4-methylenedioxymethamphetamine (MDMA) or ecstasy causes memory impairment, whereas neurogenesis improves memory and learning. Hence, this study evaluated the effects of MDMA on neurogenesis in the hippocampus of male rats.

Methods: Adult male Wistar rats received Intraperitoneal (IP) injections of MDMA (10 mg/ kg). We assessed nestin, sex-determining region Y-box 2 (Sox2), and NeuroD expressions according to the immunohistochemistry analyses.

Results: MDMA reduced the expressions of nestin, Sox2, and NeuroD compared with the control groups. The reduction in NeuroD expression was age-related.

Conclusion: MDMA possibly has negative effects on neurogenesis, which specifically results from impaired survival of newborn cells.

Soleimani Asl, S., Ghasemi Moravej, F., Kowsari, G., Farhadi, M. H., Pourhaydar, B., Ghasemi Hamidabadi, H., & Mehdizadeh, M. (2020). The Effects of 3,4-methylenedioxymethamphetamine on Neurogenesis in the Hippocampus of Male Rats. Basic and clinical neuroscience, 11(4), 457–464. https://doi.org/10.32598/bcn.9.10.420

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Synthesis and characterization of high-purity N,N-dimethyltryptamine hemifumarate for human clinical trials

Abstract

Since 2006, there has been a resurgent interest in the pharmacology and therapeutics of psychedelic drugs. Psilocybin, the 4-phosphoryl ester of N,N-dimethyltryptamine (DMT), has been studied most often, but DMT itself is also appealing because of its brief but profound psychological effects and its presence as an endogenous substance in mammalian brain. Although there have been a few studies of ayahuasca, a DMT-containing water infusion, only one human study with pure DMT has been reported since the early 2000s. Newly planned clinical trials to assess the safety and efficacy of DMT in humans with major depressive disorders require high-purity water-soluble DMT for intravenous administration. Accordingly, we synthesized and characterized DMT hemifumarate for these upcoming studies. The synthetic approach of Speeter and Anthony was slightly modified to gain some efficiency in time. In particular, this is the first known report to use aluminum hydride, generated in situ from lithium aluminum hydride, to reduce the intermediate 2-(1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide to DMT. A quench protocol was developed to produce a good yield of exceptionally pure free base DMT upon workup, which was then converted to the hemifumarate salt. Analysis of the final product included differential scanning calorimetry, thermogravimetric analysis, gas chromatography-mass spectrometry (GC-MS), 1 H and 13 C nuclear magnetic resonance spectroscopy, high-performance liquid chromatography, residual solvent analysis by GC headspace sampling, X-ray powder diffraction analysis, and residual lithium analysis by inductively coupled plasma-mass spectrometry. The DMT hemifumarate was minimally 99.9% pure, with no significant impurities or residual solvents, thus meeting regulatory standards for administration to humans.

Cozzi, N. V., & Daley, P. F. (2020). Synthesis and characterization of high‐purity N, N‐dimethyltryptamine hemifumarate for human clinical trials. Drug Testing and Analysis12(10), 1483-1493.; 10.1002/dta.2889

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27 June - Spiritual & Existential Dimensions in Psychedelic Care: Challenges & Insights

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