In vitro assessment of the cytotoxic, genotoxic and oxidative stress effects of the synthetic cannabinoid JWH-018 in human SH-SY5Y neuronal cells

Background: JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as “spice,” “herbal incense,” or “herbal blend,” as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use. JWH-018 has qualitatively similar but quantitatively greater pharmacological effects than cannabis, leading to intoxications and even deaths. The mechanisms of action of the drug’s toxicity require research, and thus, the aim of the present study was to investigate the toxicological profile of JWH-018 in human SH-SY5Y neuronal cells. Methods: SH-SY5Y neuronal cells were exposed to increasing concentrations from 5 to 150 μM JWH-018 over 24 h. Cytotoxicity, DNA damage, the apoptotic/necrotic rate, and oxidative stress were assessed following SH-SY5Y exposure. Results: JWH-018 did not produce a significant decrease in SH-SY5Y cell viability, did not alter apoptotic/necrotic rate, and did not cause genotoxicity in SH-SY5Y cells with 24-h exposure. Glutathione reductase and catalase activities were significantly reduced; however, there was no significant change in glutathione peroxidase activity. Also, JWH-018 treatment significantly decreased glutathione concentrations, significantly increased protein carbonylation, and significantly increased malondialdehyde (MDA) concentrations. For significance, all P < 0.05. Discussion/Conclusion: JWH-018 produced oxidative stress in SH-SY5Y cells that could be an underlying mechanism of JWH-018 neurotoxicity. Additional in vivo animal and human-based studies are needed to confirm our findings.

ON THE NEED TO EXPAND THE BOUNDARIES OF ELECTRONIC DOCUMENT CIRCULATION IN CRIMINAL PROCEEDINGS OF RUSSIA, INCLUDING THE EXTENSION OF THE ELECTRONIC FORM FOR THE PROCEDURE OF APPROVAL OF PROCEDURAL ACTIONS AND DECISIONS

The article is devoted to the questions concerning electronic document circulation in criminal legal proceedings of Russia. In particular, it is a question of problems of accurate understanding of “the electronic document”, applied in criminal legal proceedings; delimitation of use of electronic document circulation in criminally-remedial relations; correction of the circle of persons, having an opportunity to use electronic documents in criminal legal proceedings. In the article, a possibility of formation of electronic materials of check of the message on a crime, and also electronic materials of ex-traditional check which is passed about the decision of a question on delivery of the person for criminal prosecution is considered. Besides, the article proves the requirement of distribution of a legal regulation of electronic document circulation on a stage of excitation of criminal case and on the manufactures covered by the international cooperation in sphere of criminally-remedial relations, including manufacture about delivery of the person for criminal prosecution and sentence execution. Arguments in favour of necessity of involving for the electronic document circulation which is carried out within the limits of criminal legal proceedings, along with judges of inspectors, investigators, public prosecutors, heads of investigatory body and chiefs of division of inquiry are resulted. The conclusion about necessity of expansion of criminally-remedial space for use of electronic document circulation is formulated. Conclusions which are done by the authors are based on the analysis of existing theoretical representations and Russian criminally-remedial legislation. Article materials are intended for students, post-graduate students, teachers of legal high schools, science officers, and also workers of law enforcement bodies.

Cardiac arrest in a young healthy male patient secondary to kratom ingestion: is this ’legal high' substance more dangerous than initially thought ?

Kratom is a psychoactive herb that has stimulant properties at low doses and has opioid-like properties at higher doses. It has been used for centuries in southeast Asia as a stimulant but has gained increasing popularity as a substitute for opioids in western countries as it is easily available. As most cases of kratom use involve other drugs too, the Food and Drug Administration (FDA) has stopped short of restricting kratom due to difficulty in assessing the adverse effects of kratom alone. We present the case of a young healthy 35-year-old man who suffered a cardiac arrest due to kratom use with no other coingestants. He was subsequently intubated and found to have systolic dysfunction and small brain infarcts. Fortunately, he made a successful recovery and was discharged after a stay at thebehavioural health centre. Our case highlights the potential adverse effects of kratom and the need to regulate its use.

New psychoactive substances: psychiatrist's view

Appearing not long ago, new psychoactive substances (designer drugs), including synthetic cannabinoids, derivatives of cathinone, phenethylamines, new stimulants, synthetic opioids, tryptamine derivatives, phencyclidine, piperazine, the GABA (A/B) receptors agonists, have become a serious problem for consumers and for physicians. Consumers of these substances are attracted primarily by the intensity of psychoactive effects, and the «legal high» declared by the black manufacturers, which indicates that significant difficulties in a laboratory identification of new surfactants. Designer drugs, when ingested, can be influenced on many neurotransmitter pathways/receptors: dopamine, cannabinoid (CB1), GABA (A/B), 5-HT2A, glutamate, and k-opioid receptors (KOR), the imbalance of which leads to the development of polymorphic psychotic disorders.