Lifetime use of MDMA/ecstasy and psilocybin is associated with reduced odds of major depressive episodes

Background: Depression is a major mental health issue worldwide, with high rates of chronicity and non-recovery associated with the condition. Existing treatments such as antidepressant medication and psychological treatments have modest effectiveness, suggesting the need for alternative interventions. Aim: The aim of this study was to examine the relationships between MDMA (3,4-methylenedioxymethamphetamine)/ecstasy and psilocybin use and major depressive episodes (MDEs). Methods: This observational study used data from a large ( N = 213,437) nationally representative sample of US adults to test the association of lifetime use of MDMA/ecstasy, psilocybin and other classic psychedelics (lysergic acid diethylamide (LSD), peyote, mescaline), other illegal substances (e.g. cocaine, phencyclidine (PCP)), and legal/medicinal substances of misuse (e.g. pain relievers, tranquilizers) with lifetime, past year, and past year severe MDEs. Results: Results revealed that lifetime MDMA/ecstasy use was associated with significantly lowered odds of a lifetime MDE (adjusted odds ratio (aOR) = 0.84; p < 0.001), past year MDE (aOR = 0.84; p < 0.001), and past year severe MDE (aOR = 0.82; p < 0.001). Psilocybin was associated with significantly lowered odds of a past year MDE (aOR = 0.90; p < 0.05) and past year severe MDE (aOR = 0.87; p < 0.05). All other substances either shared no relationship with a MDE or conferred increased odds of an MDE. Conclusions: These results suggest that MDMA/ecstasy and psilocybin use is associated with lower risk of depression. Experimental studies are needed to test whether there is a causal association between use of these compounds and the alleviation of depressive symptoms.

A Vilnius Transcript of the Health Garden: A Codicological Study

This article is devoted to the history of cultural relations between the Grand Duchy of Lithuania and Moscovian Rus’ as well as the artifacts that testify to it. The object of the research is a Vilnius transcript of the Health Garden (a translation of Gart der Gesundheit (1492) into Russian) kept in the Wróblewski Library of the Lithuanian Academy of Sciences (LMAVB RS F22–25). The aim of the article is to present a revised codicological description of the object, identifying the features of the Vilnius transcript and its links with the culture of the Grand Duchy of Lithuania. This aim is achieved by using codicological, comparative and textual methods, compiling a detailed codicological description of the copy, analyzing the architecture and internal structures of the code, and identifying differences or similarities between the Vilnius, Flor, Uvarov, and Shelonin copies of the Health Garden. Based on the gathered data, the circumstances of compiling the code are clarified. The study identified the following features of the Code. The large-scale codex, created in Moscow between the 17th and 18th centuries, is not a homogeneous object. It consists of two different editions: the index is closer to the Uvarov transcript and the main text to the Kharkov / Flor transcript. The second feature is careful preparation of the transcript. The codex was drafted as an exemplary edition of an old manuscript and is richly illustrated. Colored pigments were used for decoration, leaving traces of gilding. The edges of the Codex block were painted and decorated in ornamental prints. This allows us to consider the high social status of the client of the code. The third feature is the completeness of the text of the Vilnius copy. It consists of the most comprehensive block of indexes; the main text has been supplemented with new objects, enriched with new images; the text contains as many as 237 names of medicinal substances and 38 minerals in Russian. The remarks and additions contained in the previous transcripts became an integral part of the texts of the Vilnius transcript. The identified features, overlapping formal features, and organization scheme of the text, as well as the same manner of illustration, gave reason to search for a place where all the mentioned copies – Flor, Uvarov, Shelonin – as well as other old prints or their translations could have been seen by the creators of the Vilnius transcript. It is believed that such a place could have been the The Apothecary Chancery. Some Polonisms are found in the text; the works of authors from the Polish-Lithuanian Commonwealth were used in the Rus’ at that time and thus encourage a closer look at the translations and the search for citizens from the Polish-Lithuanian Commonwealth who could have participated in the works. The research clarifies the available knowledge about the transcript kept in Vilnius. The information gathered is expected to help book historians clarify the origin of the codex, its production environment, and its place in the Gart der Gesundheit’s line of translations and transcripts; this paper will make it possible to identify other stored fragments. The article is supplemented with a comparative table of the structure and content of the Vilnius transcript of the Health Garden and a decor picture of the code block.

Preparation and Characterization of Indomethacin Supramolecular Systems with β-Cyclodextrin in Order to Estimate Photostability Improvement

Cyclodextrins have found wide application in contemporary chemistry, pharmacy and medicine. Because of their unique properties, cyclodextrins are constantly used in research on solubility or stability improvement, as well as other physicochemical properties of medicinal substances. Indomethacin (IND) is a photolabile molecule that also attracts the interest of researchers due to its therapeutic potential and the need to overcome its problematic photosensitivity. Supramolecular complexes of indomethacin with β-cyclodextrin (CD) are already known, and they show greater stability compared to complexes with other types of cyclodextrins. So far, however, the sensitivity to light of physical mixtures and inclusion complexes in the solid phase has not been studied, and their various stoichiometries have not yet been investigated. Due to this fact, the aim of the present study is to obtain supramolecular systems (inclusion complexes and physical mixtures) of indomethacin with three different amounts of β-cyclodextrin. Assessment of the photochemical stability of indomethacin-β-cyclodextrin systems in the solid state is performed in order to find the best correlation between IND stability and the amount of CD. Comparative analysis of physicochemical degradation for stoichiometry systems [CD:IND] = [1:1], [0.5:1] and [0.1:1] is performed by using ultraviolet spectroscopy, transmission—FTIR, reflection—ATR-FTIR infrared spectroscopy and DSC calorimetry.

Preparation, Characterization and Preliminary in vivo Testing of Liposomated Antiidiotypic Antibodies Against Morphine Derivatives

Artificial membrane structures containing medicinal substances are highly promising for the development of new drugs. Liposomal preparations are actively used in medical practice due to their high efficacy and relatively low toxicity. Our aim was to encapsulate anti-idiotypic antibodies into a liposomal composition with the purpose of improving their immunogenic properties. Following the preparation of a liposomal composition by the dehydration/rehydration method using ultrasonic treatment, the size, zeta potential, and loading efficiency of liposomes were investigated. Preliminary in vivo studies were conducted to evaluate the adjuvant properties of liposomes of varying size. Loaded liposomes of the smallest diameter (about 110 nm) showed the potential of enhancing the immune response similar to that obtained using Freund’s adjuvant. These results justify further research into the properties of liposomes loaded with antibodies.

Modern possibilities of herbal medicine in the treatment of acute inflammatory diseases of the upper respiratory tract

The article provides data on the effectiveness of the use of the drug in the treatment of acute, chronic and recurrent diseases of the respiratory tract and ENT organs. The drug is an extract of Pelargonium sidoides. From the standpoint of modern pharmacology, it is known that the use of natural products based on plant materials ensures safety and the absence of pronounced side effects. The main active ingredients of pelargonium are phenolic compounds: coumarins, flavonoids and phenolic acids. The article details the biochemical and pharmacological properties of each of the above groups of compounds. It has been shown that the presence of several classes of phenolic compounds simultaneously contributes to the potentiation of the pharmacological effects of each group separately. Therefore, drug has a pronounced polytropic effect: antiviral, antibacterial, immunomodulatory, mucolytic, anti-inflammatory, antioxidant, cytoprotective. The article presents the results of numerous domestic and foreign randomized, placebo-controlled studies demonstrating its high efficacy and safety in the treatment of ENT diseases, upper respiratory tract infections and bronchitis, not only in adults, but also in children over 1 year old. On the basis of the analyzed and presented material, the authors concluded that the use of a natural-based drug in the treatment of acute respiratory infection is effective and safe, both as monotherapy and in combination with other medicinal substances. He is able to quickly eliminate not only the symptoms of inflammation, but also to support the body with any ailments of this type.

Nanodispersions of Polyelectrolytes Based on Humic Substances: Isolation, Physico-Chemical Characterization and Evaluation of Biological Activity

Natural polyelectrolytes, including in the form of complexes with colloidal particles, are increasingly used in pharmacy due to the possibility of regulated attachment of medicinal substances and their targeted delivery to the target organ. However, the formation, stability, and molecular-mass characteristics of polyelectrolyte nanodispersions (ND) vary depending on the nature and composition of the medium of their origin. This is due to the lack of standardized approaches to quality control and regulatory documentation for most natural ND. In this paper, we first introduced the isolation, followed by investigations into their physico-chemical properties and bioactivity. Using the dried droplet method, we were able to detect the “coffee ring effect”. Fractographic studies of the surface structure of EHA and FA dried samples using SEM showed its heterogeneity and the presence of submicron particles encapsulated in the internal molecular cavities of polyelectrolyte. FTIR spectroscopy revealed the ND chemical structure of benzo-α-pyron and benzo-γ-pyron, consisting of nanoparticles and a branched frame part. The main elements detected by X-ray fluorescence in humic substance extract and fulvic acid include Si, P, S, K, Ca, Mn, Fe, Cu, Zn, whereas Fe is in high concentrations. The UV-spectra and fluorescent radiation demonstrated the possibility of studying the effect of the fulvate chromone structure on its optical properties. It is shown that dilution of the initial solutions of polyelectrolytes 1:10 contributes to the detection of smaller nanoparticles and an increase in the absolute value of the negative ζ-potential as a factor of ND stability. A study of the EHS effect on the SARS-CoV-2 virus infectious titer in the Vero E6 cell showed the effective against virus both in the virucidal scheme (the SI is 11.90–22.43) and treatment/prevention scheme (the SI is 34.85–57.33). We assume that polyelectrolyte ND prevent the binding of the coronavirus spike glycoprotein to the receptor. Taking into account the results obtained, we expect that the developed approach can become unified for the standardization of the ND natural polyelectrolytes complex, which has great prospects for use in pharmacy and medicine as a drug with antiviral activity.

The Combination of Solid-State Chemistry and Medicinal Chemistry as the Basis for the Synthesis of Theranostics Platforms

This review presents the main patterns of synthesis for theranostics platforms. We examine various approaches to the interpretation of theranostics, statistics of publications drawn from the PubMed database, and the solid-state and medicinal chemistry methods used for the formation of nanotheranostic objects. We highlight and analyze chemical methods for the modification of nanoparticles, synthesis of spacers with functional end-groups, and the immobilization of medicinal substances and fluorophores. An overview of the modern solutions applied in various fields of medicine is provided, along with an outline of specific examples and an analysis of modern trends and development areas of theranostics as a part of personalized medicine.

Polymorphism control of active pharmaceutical ingredients

Рolymorphism is receiving increasing attention due to its influence on the physicochemical and pharmacological properties of the active pharmaceutical ingredients (API) while maintaining the molecular structure. This review is devoted to the problem of APIs phase state control both at the development stage and during the circulation of the drug. The term «polymorphism» has different definitions depending on the branch of science. There is no unambiguous solution to this issue in the regulatory documentation of pharmaceutical industry either. Based on the analysis of literary sources, the article presents a comparison of pharmacopeia methods, recommended in Russian and foreign regulatory documents for the analysis of polymorphism of medicinal substances, including state pharmacopeias of Russia, Belarus, Kazakhstan, the USA, and Japan, as well as international pharmacopeias of the European Economic Union and the Eurasian Economic Union. The trend on using a complex of high-tech equipment is revealed. A systematic approach to analysis based on X-ray diffraction, thermal, spectral, microscopic, biological, and physical methods for determining constants makes it possible not only to identify the polymorphic modification of API, but also to characterize its structure, morphology, physicochemical properties and pharmacological activity. In the Russian Federation, the phenomenon of polymorphism is being studied especially intensively, and some control methods, such as biological methods, are validated only in Russian pharmacopeia. A promising direction for further research is the improvement and harmonization of regulatory documentation within the framework of this chemical and technological field of pharmacy. A global approach will help to reduce not only the probability of poor-quality products entering the market, but also the costs of establishing the authenticity of the active pharmaceutical ingredient produced.

Application of the high-resolution HPLC–MS/MS method for identification and quantitative determination of impurities in the substance of the drug «Lomustine»

Due to the state program of the Russian Federation "Development of the pharmaceutical and medical industry" (Pharma-2020), extended until 2024, the interest in the possibility of organizing the production and quality control of imported medicinal substances directly on the territory of the Russian Federation has significantly increased. In this case, the drugs included in the lists of "Indispensible and essential drugs" and "Provision of necessary drugs" [1] are of particular importance. One of the drugs often used in the chemotherapy of malignant tumors is the drug "Lomustine", which includes 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea as an active ingredient [1-3].