Martin Kuchar

University of Chemistry and Technology, Prague | VSCHT · Department of Chemistry of Natural Compounds

Introduction: An altered neurodevelopmental trajectory associated with prenatal exposure to ∆-9-tetrahydrocannabinol (THC) leads to aberrant cognitive processing through a perturbation in the effectors of hippocampal plasticity in the juvenile offspring. As adolescence presents a unique window of opportunity for “brain reprogramming”, we aimed at a...

Alcohol binge drinking is common among adolescents and may challenge the signalling systems that process affective stimuli, including calcitonin gene-related peptide (CGRP) signalling. Here, we employed a rat model of adolescent binge drinking to evaluate reward-, social- and aversion-related behaviour, glucocorticoid output and CGRP levels in affe...

Ghrelin je hormon, který u člověka podporuje chuť k jídlu, a je proto někdy označován jako „hormon hladu“. V lidském organismu se váže na receptor GHS-R1a, což vede k uvolňování růstového hormonu. Sektretagoga růstového hormonu (growth hormone secretagogues, GHSs) jsou skupina látek, které interagují s receptorem GHS-R1a podobně jako ghrelin, a pod...

Introduction Psilocybin is one of the most extensively studied psychedelic drugs with a broad therapeutic potential. Despite the fact that its psychoactivity is mainly attributed to the agonism at 5-HT 2A receptors, it has high binding affinity also to 5-HT 2C and 5-HT 1A receptors and indirectly modulates the dopaminergic system. Psilocybin and it...

Psilocybin is investigated as a fast-acting antidepressant used in conjunction with psychotherapy. Intact cognitive functions, including memory, are one of the basic conditions of effective psychedelic-assisted therapy. While cognitive and memory processing is attenuated on various domains during psilocybin intoxication, the effect of psilocybin on...

Recently, the number of structural modifications of synthetic cathinones has been growing making them the second largest group of new psychoactive substances in Europe. Although they are abused because of their various psychoactive effects, some compounds from this group also serve as pharmaceuticals. Since synthetic cathinones are chiral molecules...

An increasing number of products containing synthetic cannabinoids pose a growing crisis to public health worldwide. Recently, a rising number of cases of serious adverse health effects, intoxications, and death cases associated with synthetic cannabinoids were reported. The current study represents the comprehensive structural analysis of three ne...

Introduction: N-2-methoxy-benzylated (“NBOMe”) analogues of phenethylamine are a group of new psychoactive substances (NPS) with reported strong psychedelic effects in sub-milligram doses linked to a number of severe intoxications, including fatal ones. In our present work, we provide a detailed investigation of pharmacokinetics and acute behaviour...

Na celosvětovém trhu dochází k rapidnímu nárůstu padělaných farmak na léčbu erektilní dysfunkce, které jsou k dostání pouze na lékařský předpis. Obsah jejich účinné látky bývá několikrát překročen, nebo účinná látky zcela chybí. Tyto padělky obsahují nejrůznější příměsi a doposud neprostudované strukturní deriváty původních sloučenin, což představu...

Previous evidence suggests that prenatal exposure to THC (pTHC) derails the neurodevelopmental trajectories towards a vulnerable phenotype for impaired emotional regulation and limbic memory. Here we aimed to investigate pTHC effect on hippocampus-related cognitive functions and markers of neuroplasticity in adolescent male offspring. Wistar rats w...

Adolescent exposure to cannabinoids as a postnatal environmental insult may increase the risk of psychosis in subjects exposed to perinatal insult, as suggested by the two-hit hypothesis of schizophrenia. Here, we hypothesized that peripubertal Δ9-tetrahydrocannabinol (aTHC) may affect the impact of prenatal methylazoxymethanol acetate (MAM) or per...

This work presents a potentiometric approach for the detection of two cathinone derivatives, namely mephedrone (4‐MMC) and clephedrone (4‐CMC). Contrary to neutral‐carriers (dibenzo‐18‐crown‐6‐ether and calix[4]arene), cation‐exchanger (tetraphenylborate sodium) as active component of ion‐selective membrane showed near‐Nernstian response (+47 mV/de...

Methoxphenidine was originally patented for its properties to treat neurotoxic injury. However, due to the side effects, it failed to become pharmaceutic and later reappeared on the black market among...

After cannabis, the most commonly used illicit substance worldwide is amphetamine and its derivatives, such as methamphetamine, with an ever-increasing number of synthetic modifications. Thus, fast and reliable methods are...

The ongoing Covid-19 pandemics showed the need for the effective decontamination of environment and surfaces. One of the options could be the use of gas ozone. Ozone has been well known for its disinfection properties, which were in the past used to decontaminate water. In this article, we present a development of an easy-made and ready-to-use port...

New psychoactive substances and among them synthetic cathinones represent a significant threat to human health globally. However, within such a large pool of substances derived from a natural compound ((S)-cathinone), substances with important pharmaceutical uses can be identified, as already documented by bupropione. Therefore, this work aimed to...

Since not only psilocybin (PSB) but also PSB-containing mushrooms are used for psychedelic therapy and microdosing, it is necessary to know their concentration variability in wild-grown mushrooms. This article aimed to determine the PSB, psilocin (PS), baeocystin (BA), norbaeocystin (NB), and aeruginascin (AE) concentrations in a large sample set o...

Classified as an adaptogen, Maral root (Rhaponticum carthamoides, Leuzea carthamoides) is a herb that has long been used in Siberian as well as Russian alternative medicine. With over 200 substances found, this plant is a great source of bioactive compounds which have significant beneficial effects on human health and physical enhancement. Simultan...

Background Alcohol binge drinking may compromise the functioning of the nucleus accumbens (NAc), i.e. the neural hub for processing reward and aversive responses. Methods As socially stressful events pose particular challenges at developmental stages, this research applied the resident–intruder paradigm as a model of social stress, to highlight be...

Rationale: Serotonergic psychedelics are being studied as novel treatments for mental health disorders and as facilitators of improved well-being, mental function, and creativity. Recent studies have found mixed results concerning the effects of low doses of psychedelics ("microdosing") on these domains. However, microdosing is generally investiga...

N-(2-methoxybenzyl)phenethylamines (NBOMes) are a family of potent 5-HT2A agonists containing substances emerging on the illicit drug market as a replacement for N,N-diethyllysergamide (LSD). Despite the increasing use of NBOMes for diagnostic, research and recreational purposes, only a limited number of studies have focussed on their in vivo effec...

Aim Novel benzodiazepines, emerged on the recreational drug market in past few years, have caused serious problems in many countries, including intoxications and fatalities. Not only, that limited information is still available on their dosage, the situation may be even more complicated if a combination of these designer drugs occurs. Method For i...

Aim Ostarine, also called enobosarm or MK-2866, is one of the Selective Androgen Receptor Modulators (SARMs). A number of preclinical data suggest the beneficial use of these substances to increase muscle mass growth and bone density. Unlike anabolic steroids, they have suppressed androgenic side effects and are therefore thought to be useful in th...

Aim Endocrine disruptors (EDs) are a group of organic pollutants, which have negative effect on the hormonal systems of organism. For example, they can be toxic for the hormonal systems in fish, resulting in decrease in fertility. Conventional wastewater treatment is not successful in removal of EDs, therefore heterogenous photocatalysis is studied...

Aim Deschloroketamine (DCK), a structural analogue of ketamine, has recently emerged on the illicit drug market as a recreational drug with a modestly long duration of action. Despite it being widely used by recreational users, no systematic research on its effects has been performed to-date. For this reason, we investigated the pharmacokinetic, ph...

Aim Frequent detection of antibiotics in aquatic environment represents a global ecologic problem due to the fact, that these compounds are not fully biodegradable during conventional purification processes in wastewater treatment plants. The presence of antibiotics cause that the bacteria present in water and in animal or human bodies build resist...

Aim The increasing prevalence of New Psychoactive Substances (NPS) on the drug market exerts considerable pressure on the development of novel detection techniques, especially those suitable for analyses directly on a crime scene. Raman and IR spectroscopy usually fulfil such needs; however, they have limitations (e.g. fluorescence in Raman and som...

Aim Methoxphenidine (MXP) is new psychoactive substance belonging to the group of dissociative anesthetics. It appeared on the black market in 2013, and MXP intoxications have been reported with at least three deaths since then. To understanding the mechanism of toxicity and effects of MXP, it is important to know its pharmacological properties (e....

Aim Methoxphenidine (MXP) belongs among dissociative anesthetics from the group of new psychoactive substances. According to the unofficial user experiences, MXP is less active than common dissociative anesthetics like ketamine, yet, several intoxications were associated with this substance up to this date. Within our previous work, we discovered t...

The objective of this prospective study was to examine the exposure to the main active metabolites of ciprofloxacin in critically ill patients and to examine the factors (demographic, laboratory and genetic) that could potentially affect the drug metabolic conversion of ciprofloxacin. The secondary aim was to develop a population pharmacokinetic mo...

The use of low sub-perceptual doses of psychedelics (“microdosing”) has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies severely limits our knowledge of microdosing and its effects. Moreover, research conducted in standard laboratory settings...

Psilocybin is a classical serotoninergic psychedelic that induces cognitive disruptions similar to psychosis. Gamma activity is affected in psychosis and is tightly related to cognitive processing. The 40 Hz auditory steady-state responses (ASSR) are frequently used as indicators to test the ability to generate gamma activity. Based on previous lit...

Contactless digital tags are increasingly penetrating into many areas of human activities. Digitalization of our environment requires an ever growing number of objects to be identified and tracked with machine-readable labels. Molecules offer immense potential to serve for this purpose, but our ability to write, read, and communicate molecular code...

There is an increased societal trend to engage in microdosing, in which small sub-hallucinogenic amounts of psychedelics are consumed on a regular basis. Following subjective reports that microdosing enhances the experience of nature and art, in the present study we set out to study the effects of psilocybin microdosing on feelings of awe and art p...

Serotonergic psychedelics are being studied as novel treatments for mental health disorders and as facilitators of improved well-being, mental function and creativity. Recent studies have found mixed results concerning the effects of low doses of psychedelics (microdosing) on these domains. However, microdosing is generally investigated using instr...

The black market for new psychoactive substances has been constantly evolving and the substances that appear on this market cause a considerable number of issues, in extreme cases leading to human deaths. While monitoring the drug black market, we detected a sample of a dissociative anesthetic methoxphenidine, the salt of which contained an unusual...

Background Microdoses of psychedelics (i.e. a sub-hallucinogenic dose taken every third day) can reduce symptoms of depression, anxiety and stress according to anecdotal reports and observational studies. Research with medium to high doses of psilocybin points towards potential underlying mechanisms, including the modulation of emotion and interoce...

Kynurenic acid is a neuroprotective metabolite of tryptophan formed by kynurenine aminotransferase (KAT) catalyzed transformation of kynurenine. However, its high brain levels are associated with cognitive deficit and with the pathophysiology of schizophrenia. Although several classes of KAT inhibitors have been published, the search for new inhibi...

The use of low sub-hallucinogenic doses of psychedelics (microdosing) has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies limits our knowledge of microdosing and its effects. Moreover, research conducted in laboratory settings might fail to c...

Naphyrone, also known as NRG-1, is a novel psychoactive substance (NPS), a cathinone with stimulatory properties available on the grey/illicit drug market for almost a decade. It is structurally related to infamously known powerful stimulants with the pyrovalerone structure, such as alpha-pyrrolidinovalerophenone (α-PVP) or methylenedioxypyrovalero...

Breast milk analysis provides useful information about acute newborn exposure to harmful substances, such as psychoactive drugs abused by a nursing mother. Since breast milk represents a complex matrix with large amounts of interfering compounds, a comprehensive sample pre-treatment is necessary. This work focuses on determination of amphetamines a...

Compounds from the N-benzylphenethylamine (NBPEA) class of novel psychoactive substances are being increasingly utilized in neurobiological and clinical research, as diagnostic tools, or for recreational purposes. To understand the pharmacology, safety, or potential toxicity of these substances, elucidating their metabolic fate is therefore of the...

The consumption of psychoactive substances is a worldwide problem and the sheer number of their seizures is alarming. These substances also include the synthetic drug 3,4–methylenedioxy-N-methylamphetamine (MDMA), also known as ecstasy, which is very often abused and widespread around the world. The number of ecstasy tablet seizures testifies to th...

High concentrations of pharmaceuticals have been detected in greywater effluents treated using up-to-date technologies. Finding a suitable additional treatment before this effluent is reused is urgently needed to ensure the reused water meets quality standards. This paper reports the use of heterogeneous photocatalysis on anatase and rutile nanopow...

Binge alcohol consumption among adolescents affects the developing neural networks underpinning reward and stress processing in the nucleus accumbens (NAc). This study explores in rats the long-lasting effects of early intermittent exposure to intoxicating alcohol levels at adolescence, on: (1) the response to natural positive stimuli and inescapab...

Background and purpose: Deschloroketamine (DCK), a structural analogue of ketamine, has recently emerged on the illicit drug market as a recreational drug with a modestly long duration of action. Despite it being widely used by recreational users, no systematic research on its effects has been performed to-date. Experimental approach: Pharmacoki...

The dubious online market in phosphodiesterase type 5 inhibitors is growing on a global scale. Counterfeit medical products can represent health issues for the user and cause medical mistrust. Within this work, genuine Cialis containing the active pharmaceutical ingredient (API) tadalafil, its generics available in the Czech Republic and the Cialis...

A long-term exposition of antibiotics represents a serious problem for the environment, especially for human health. Heterogeneous photocatalysis opens a green way for their removal. Here, we correlated the structural-textural properties of TiO2 photocatalysts with their photocatalytic performance in ampicillin abatement. The tested nanoparticles i...

The aim of this prospective PK study was to evaluate the pharmacokinetics of ciprofloxacin dosed within the first 36 h (early phase) and after 3 days of treatment (delayed phase) using individual and population PK analysis. The secondary aim of the study was to evaluate possible dosing implications of the observed PK differences between early and d...

Introduction: Microdosing refers to the repetitive administration of tiny doses of psychedelics (LSD, Psilocybin) over an extended period of time. This practice has been linked to alleged cognitive benefits, such as improved mood and creativity, potentiated by targeting serotonergic 5-HT2A receptors and facilitating cognitive flexibility. Nonethele...

The synthetic drug 3,4-methylenedioxy-N-methyl-amphetamine (MDMA), also known as ecstasy, is one of the most abused dance drugs spread around the world. The number of seizures of ecstasy tablets increases every year. As MDMA is a chiral substance with one chiral center, it may occur as two enantiomers. These enantiomers have different physiological...

N-Benzylphenethylamines are novel psychedelic substances increasingly used for research, diagnostic, or recreational purposes. To date, only a few metabolism studies have been conducted for N-2-methoxybenzylated compounds (NBOMes). Thus, the available 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe) metabolism data are lim...

Stability studies represent an essential component of pharmaceutical development, enabling critical evaluation of the therapeutic potential of an active pharmaceutical ingredient (API) or a final pharmaceutical product under the influence of various environmental factors. The aim of the present study was to investigate the chemical stability of can...

Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechani...

The aim of this work is to develop an impedimetric sensor using the principle of host-guest interaction for the detection of new psychoactive substances (NPSs). Synthesized 4′-(N-3-thiophenecarboxamido)benzo-15-crown-5 (TH3CA4AB15C5) was electrochemically deposited on the surface of a platinum disc electrode using cyclic voltammetry. Spectroscopic...

Perinatal exposure to Δ9-tetrahydrocannabinol (THC) affects brain development and might increase the incidence of psychopathology later in life, which seems to be related to a dysregulation of endocannabinoid and/or dopaminergic systems. We here evaluated the transcriptional regulation of the genes encoding for the cannabinoid CB1 receptor (Cnr1) a...

New psychoactive substances (NPSs) have become a popular alternative to illicit drugs of abuse. However, to determine their metabolic pathways in the human organism, a detailed knowledge of their structure is crucial. Here, we present a comprehensive spectroscopic structural study of the synthetic cathinones (clephedrone, flephedrone, brephedrone)...

We present a novel series of radioiodinated tracers and potential theranostics for diseases accompanied by pathological function of proteins involved in choline transport. Unlike choline analogues labeled with 11C or 18F that are currently used in the clinic, the iodinated compounds described herein are applicable in positron emission tomography, s...

Psilocybin, psilocin, baeocystin, norbaeocystin, and aeruginascin are tryptamines structurally similar to the neurotransmitter serotonin. Psilocybin and its pharmacologically active metabolite psilocin in particular are known for their psychoactive effects. These substances typically occur in most species of the genus Psilocybe (Fungi, Strophariace...

The dark web scene has been drawing the attention of law enforcement agencies and researchers alike. To date, most of the published works on the dark web are based on data gained by passive observation. To gain a more contextualized perspective, we conducted a study in which we selected three vendors on the ‘Dream Market’ dark web marketplace, from...

Mephedrone, a psychoactive compound derived from cathinone, is widely used as a designer drug. The determination of mephedrone and its metabolites is important for understanding its possible use in medicine. In this work, a method of capillary electrophoresis for the chiral separation of mephedrone and its metabolites was developed. Carboxymethylat...

New psychoactive substances (NPSs) are associated with a significant number of intoxications. With the number of readily available forms of these drugs rising every year, there are even risks for the general public. Consequently, there is a high demand for methods sufficiently sensitive to detect NPSs in samples found at the crime scene. Infrared (...

We have recently encountered a particularly concerning exemplars of counterfeit benzodiazepines, upon which we wish to report. The herein described Diazepam pills are very convincing counterfeits of a global pharmaceutical manufacturer, yet they contain a different Active Pharmaceutical Ingredient (API) ‐ etizolam. A bulk of over one million of the...

In the past two decades, supercritical fluid chromatography has evolved from a niche application to a comprehensive technology and a fully-fledged alternative to conventional high-performance liquid chromatography. Due to high miscibility of supercritical carbon dioxide with common organic solvents, the supercritical fluid chromatography offers a b...

Cannabidiol (CBD), a major non-psychoactive cannabinoid, has received a lot of attention due to its potential anti-inflammatory, pain-relieving, and anti-anxiety properties. This has led to a recent boom in CBD-rich commercial products, which are sold without prescription in the form of oils, candies, and cosmetics. Since these products are derived...

Naphthylpyrovalerone (naphyrone) is a pyrovalerone cathinone that potently inhibits monoamine transporters and provides stimulatory‐entactogenic effects. Little is known about the safety of naphyrone or its effects in vivo, and more research is needed to acquire knowledge about its fundamental effects on physiology and behaviour. Our objective was...

A single dose of the serotonin 2A receptor (5-HT2AR) agonist psilocybin can have long-lasting beneficial effects on mood, personality, and potentially on mindfulness, but underlying mechanisms are unknown. Here, we for the first time conduct a study that assesses psilocybin effects on cerebral 5-HT2AR binding with [¹¹C]Cimbi-36 positron emission to...

In this work, the 3-D structure of the well-known opioid drug heroin in a solution was investigated. The goal was to provide a complete and detailed description of the stable conformers with their relative abundances. This knowledge is very important from the pharmaceutical and forensic point of view as it could help significantly with deeper under...

Cannabis is a plant containing a mixture of chemical substances of unique composition, and therefore it has vast array of applications. Hemp fiber and shives are used in the paper, construction and textile industries. Hemp seeds and products have high nutritional value for humans. They contain significant amounts of essential amino acids and repres...