Psychopharmacological Effects Research Articles

Mexican calea (Calea zacatechichi Schltdl.) interferes with cholinergic and dopaminergic pathways and causes neuroglial toxicity

Ethnopharmacological relevanceThe use of “Mexican calea” (Calea zacatechichi Schltdl.) in ritualistic ceremonies, due to its dream-inducing effects, was until recently limited to indigenous communities in Mexico. However, the plant has recently gained popularity in Western societies being commonly used in recreational settings. Despite the traditional and recreational uses, mechanisms underlying its reported oneirogenic effects remain unknown, with no data available on its neurotoxic profile. Aim of the studyThe scarcity of toxicological data and the unknown role of major neurotransmitter systems in the dream-inducing properties of the plant prompted us to investigate which neurotransmitters might be affected upon its consumption, as well as the potential cytotoxic effects on neurons and microglial cells. Furthermore, we aimed to explore a relationship between the recorded effects and specific constituents. Materials and methodsEffects on cholinergic and monoaminergic pathways were investigated using enzymatic assays, with the latter also being conducted in neuronal SH-SY5Y cells along with the impact on glutamate-induced excitotoxicity. Investigation of the neurotoxic profile was approached in neuronal SH-SY5Y and microglial BV-2 cells, evaluating effects on metabolic performance and membrane integrity using MTT and LDH leakage assays, respectively. Potential interference with oxidative stress was monitored by assessing free radical's levels, as well as 5-lipoxygenase mediated lipid peroxidation. Phenolic constituents were identified through HPLC-DAD-ESI(Ion Trap)MSn analysis. ResultsBased on the significant inhibition upon acetylcholinesterase (p < 0.05) and tyrosinase (IC50 = 60.87 ± 7.3 μg/mL; p < 0.05), the aqueous extract obtained from the aerial parts of C. zacatechichi interferes with the cholinergic and dopaminergic systems, but has no impact against monoamine oxidase A. Additionally, a notable cytotoxic effect was observed in SH-SY5Y and BV-2 cells at concentrations as low as 125 and 500 μg/mL (p < 0.05), respectively, LDH leakage suggesting apoptosis may occur at these concentrations, with necroptosis observed at higher ones. Despite the neurocytotoxic profile, these effects appear to be independent of radical stress, as the C. zacatechichi extract scavenged nitric oxide and superoxide radicals at concentrations as low as 62.5 μg/mL, significantly inhibiting also 5-lipoxygenase (IC50 = 72.60 ± 7.3 μg/mL; p < 0.05). Qualitative and quantitative analysis using HPLC-DAD-ESI(Ion Trap)MSn enabled the identification of 28 constituents, with 24 of them being previously unreported in this species. These include a series of dicaffeoylquinic, caffeoylpentoside, and feruloylquinic acids, along with 8 flavonols not previously known to occur in the species, mainly 3-O-monoglycosylated derivatives of quercetin, kaempferol, and isorhamnetin. ConclusionsOur findings regarding the neuroglial toxicity elicited by C. zacatechichi emphasize the necessity for a thorough elucidation of the plant's toxicity profile. Additionally, evidence is provided that the aerial parts of the plant inhibit both acetylcholinesterase and tyrosinase, potentially linking its psychopharmacological effects to the cholinergic and dopaminergic systems, with an apparent contribution from specific phenolic constituents previously unknown to occur in the species. Collectively, our results lay the groundwork for a regulatory framework on the consumption of C. zacatechichi in recreational settings and contribute to elucidating previous contradictory findings regarding the mechanisms underlying the dream-inducing effects of the plant.

Drug-drug interactions of plant alkaloids derived from herbal medicines on the phase II UGT enzymes: an introductory review.

Herbal medicines are widely used as alternative or complementary therapies to treat and prevent chronic diseases. However, these can lead to drug-drug interactions (DDIs) that affect the glucuronidation reaction of UDP glucuronosyltransferases (UGTs), which convert drugs into metabolites. Plant extracts derived from medicinal herbs contain a diverse array of compounds categorized into different functional groups. While numerous studies have examined the inhibition of UGT enzymes by various herbal compounds, it remains unclear which group of compounds exerts the most significant impact on DDIs in the glucuronidation reaction. Recently, alkaloids derived from medicinal herbs, including kratom (Mitragyna speciosa), have gained attention due to their diverse pharmacological properties. This review primarily focuses on the DDIs of plant alkaloids from medicinal herbs, including kratom on the phase II UGT enzymes. Kratom is a new emerging herbal product in Western countries that is often used to self-treat chronic pain, opioid withdrawal, or as a replacement for prescription and non-prescription opioids. Kratom is well-known for its psychoactive alkaloids, which have a variety of psychopharmacological effects. However, the metabolism mechanism of kratom alkaloids, particularly on the phase II pathway, is still poorly understood. Simultaneously using kratom or other herbal products containing alkaloids with prescribed medicines may have an impact on the drug metabolism involving the phase II UGT enzymes. To ensure the safety and efficacy of treatments, gaining a better understanding of the DDIs when using herbal products with conventional medicine is crucial.

Potential effect of ketamine in treatment for dextromethorphan use disorder exploding in Japanese young population

In Japan, the landscape of clinical practice for substance use disorder is changing significantly, primarily due to an increase in patients using over-the-counter drugs. A major concern is the rising number of patients misusing dextromethorphan (DXM). These patients with DXM use disorders often have severe trauma-related and mood symptoms, and therefore try to cope with those symptoms by self-medicating with DXM. In this article, we propose that ketamine, which has similar psychopharmacological effects to DXM, may be a useful alternative pharmacological treatment for these patients.

Technical and health governance aspects of the external quality assessment system for classical and new psychoactive substances analysis testing in blood

New psychoactive substances (NPS) are uncontrolled analogues of existing drugs or newly synthesized chemicals that exhibit psychopharmacological effects. Due to their diverse nature, composition, and increasing prevalence, they present significant challenges to the healthcare system and drug control policies. In response, healthcare system laboratories have developed analytical methods to detect NPS in biological samples. As a Regional Reference Centre, the Sicilian CRQ Laboratory (Regional Laboratory for Quality Control) developed and conducted an External Quality Assessment (EQA) study to assess, in collaboration with the Istituto Superiore di Sanità (ISS), the ability of different Italian laboratories to identify NPS and traditional drugs of abuse (DOA) in biological matrices.Two blood samples were spiked with substances from various drug classes, including synthetic cannabinoids, cathinones, synthetic opiates, and benzodiazepines, at concentrations ranging from 2 to 10 ng/mL. The blood samples were freeze-dried to ensure the stability of DOA and NPS. Twenty-two laboratories from the Italian healthcare system participated in this assessment. The information provided by the laboratories during the registration in an in-house platform included a general description of the laboratory, analytical technique, and the chosen panels of analytes. The same platform was employed to collect and statistically analyze the data and record laboratory feedback and comments.The evaluation of the results revealed that the participating laboratories employed three different techniques for analyzing the samples: GC-MS, LC-MS, and immunoenzymatic methods. Approximately 90 % of the laboratories utilized LC-MS techniques. Around 40 % of false negative results were obtained, with the worst results in the identification of 5-chloro AB PINACA. The results showed that laboratories that used LC-MS methods obtained better specificity and sensitivity compared to the laboratories using other techniques.The results obtained from this first assessment underscore the importance of external quality control schemes in identifying the most effective analytical techniques for detecting trace molecules in biological matrices. Since the judicial authorities have not yet established cut-off values for NPS, this EQA will enable participating laboratories to share their analytical methods and expertise, aiming to establish common criteria for NPS identification.

A Meta-Analysis of fMRI Activation Studies of Ketamine in Healthy Participants

IntroductionThere has been rapidly growing interest in understanding the pharmaceutical and clinical properties of psychedelic and dissociative drugs, with a particular focus on ketamine. This compound, long known for its anesthetic and dissociative properties, has garnered attention due to its potential to rapidly alleviate symptoms of depression, especially in individuals with treatment-resistant depression (TRD) or acute suicidal ideation or behavior. However, while ketamine’s psychopharmacological effects are increasingly well-documented, the specific patterns of its neural impact remain a subject of exploration and basic questions remain about its effects on functional activation in both clinical and healthy populations.ObjectivesThis meta-analysis seeks to contribute to the evolving landscape of neuroscience research on dissociative drugs such as ketamine by comprehensively examining the effects of acute ketamine administration on neural activation, as measured by functional magnetic resonance imaging (fMRI), in healthy participants.MethodsWe conducted a meta-analysis of existing fMRI activation studies of ketamine using multilevel kernel density analysis (MKDA). Following a comprehensive PubMed search, we quantitatively synthesized all published primary fMRI whole-brain activation studies of the effects of ketamine in healthy subjects with no overlapping samples (N=18). This approach also incorporated ensemble thresholding (α=0.05-0.0001) to minimize cluster-size detection bias and Monte Carlo simulations to correct for multiple comparisons.ResultsOur meta-analysis revealed statistically significant (p&lt;0.05-0.0001; FWE-corrected) alterations in neural activation in multiple cortical and subcortical regions following the administration of ketamine to healthy participants (N=306).ConclusionsThese results offer valuable insights into the functional neuroanatomical effects caused by acute ketamine administration. These findings may also inform development of therapeutic applications of ketamine for various psychiatric and neurological conditions. Future studies should investigate the neural effects of ketamine administration, including both short-term and long-term effects, in clinical populations and their relation to clinical and functional improvements.Disclosure of InterestNone Declared

The novel psychoactive substance 25E-NBOMe induces reward-related behaviors via dopamine D1 receptor signaling in male rodents.

Novel psychoactive substances (NPSs) are new psychotropic drugs designed to evade substance regulatory policies. 25E-NBOMe (2-(4-ethyl-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine) has recently been identified as an NPS, and its recreational misuse has been reported to be rapidly increasing. However, the psychopharmacological effects and mechanisms of 25E-NBOMe have not been studied. We examined the abuse potential of 25E-NBOMe using the conditioned place preference in male mice and self-administration paradigms in male rats. Additionally, immunoblot assay, enzyme-linked immunosorbent assay, and microdialysis were used to determine the molecular effects of 25E-NBOMe in the nucleus accumbens (NAc). Our data demonstrated that 25E-NBOMe induces conditioned place preference, and the dopaminergic signaling in the NAc mediates these. Following 25E-NBOMe administration, expression of dopamine transporter and dopamine D1 receptor (D1DR) were enhanced in the NAc of male mice, and NAc dopamine levels were reduced in both male mice and rats. Induction of intracellular dopaminergic pathways, DARPP32, and phosphorylation of CREB in the NAc of male mice was also observed. Significantly, pharmacological blockade of D1DR or chemogenetic inhibition of D1DR-expressing medium spiny neurons in the NAc attenuated 25E-NBOMe-induced conditioned place preference in male mice. We also examined the hallucinogenic properties of 25E-NBOMe using the head twitch response test in male mice and found that this behavior was mediated by serotonin 2A receptor activity. Our findings demonstrate that D1DR signaling may govern the addictive potential of 25E-NBOMe. Moreover, our study provides new insights into the potential mechanisms of substance use disorder and the improvement of controlled substance management.

Review of the Efficacy and Safety of Cannabidiol with a Focus on Children and Adolescents in the Treatment of Psychiatric Symptoms and Disorders

Abstract: Cannabidiol (CBD) is a plant-derived cannabinoid found in cannabis and hemp plants with broad psychopharmacologic effects and poorly understood mechanisms of action that may include antioxidant and anti-inflammatory properties and central nervous system (CNS) modulation of endocannabinoid, glutamatergic, and serotonergic neurotransmission. This article reviews existing data on the safety and efficacy of CBD for mental and physical health indications in the pediatric population and for psychiatric disorders in adults, with a focus on clinical trials. Searches of PubMed and PsycINFO for articles through October 2021 focused on clinical trials on “cannabidiol” and “seizure” or “psychiatry” in youth and adults, identifying 686 articles that were then screened and evaluated for relevance. Research into the safety and efficacy of CBD led to the United States Food and Drug Administration's approval of Epidolex, a purified pharmaceuticalgrade CBD medicine, for treating drug-resistant seizures in Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. Beyond treatment for rare seizure disorders, CBD has received growing public interest in recent years as a “natural” treatment for various other medical and psychiatric conditions, resulting in a rapidly expanding multi-billion-dollar US market for CBD dietary/health supplements and a growing number of Americans reporting regular use. However, the growing demand and broad claims of purported benefits have greatly outpaced the body of literature substantiating its use. Further, limited safety data in pediatric populations, drug-to-drug interactions between CBD and prescribed medications, and issues related to mislabeling and contamination have blunted enthusiasm for CBD in the pediatric healthcare community and indicate a need for additional research.

Examining acute psychopharmacological effects of nicotine vaping versus heated tobacco products in a randomised crossover study of product naïve adult smokers

Nicotine vaping products (NVPs) and heated tobacco products (HTPs) are designed to replicate the sensory and behavioural aspects of smoking cigarettes while avoiding combustion. The success of these products as harm reduction tools will partially depend on their ability to satisfy smokers and alleviate nicotine-related withdrawal symptoms. This study aims to compare short-term effects of NVPs (Juul and Aspire PockeX) versus HTPs (IQOS) on smoking-related withdrawal relief, product satisfaction, intention to switch to NVP/HTP, perceptions and attitudes in UK adult cigarette smokers naïve to these products. In a randomized cross-over study, 45 participants visited the lab twice, at each visit trying one of the two products (NVP/HTP) and completing a questionnaire. Responses were normalized on a 0–100% scale and mean differences (MD) between NVP and HTP scores computed, with positive and negative MD values indicating greater endorsement for NVP and HTP, respectively. Cigarette cravings were reduced similarly (~ 20.0%) by both products (MD = 4.5%, 95%Confidence Interval (CI) − 4.8, 13.8). Direct positive effects (MD = − 3.5%, 95%CI − 7.2, 0.2) and adverse side effects (MD = 1.8%, 95%CI − 0.3, 3.8) were comparable after each product use, though marginally favouring HTPs. HTPs were perceived as more satisfying overall (MD = − 13.2%, 95%CI − 20.3 − 6.1) than NVPs but both were perceived as similarly addictive (MD = 3.6%, 95%CI − 4.6, 11.8), relative to cigarettes. Intention to switch to either product was comparable (MD = 4.0%, 95%CI − 5.7, 13.8). Comparison of acute use of NVP versus HTP in a sample of UK smokers naïve to these products suggests that HTPs are perceived as more satisfying than NVPs, though still less satisfying than cigarettes.Registration: The analysis plan was pre-registered, and it is available at https://osf.io/6ymdu

Design, Synthesis, and Biological Studies of Flavone-Based Esters and Acids as Potential P450 2A6 Inhibitors.

As a potential means for smoking cessation and consequently prevention of smoking-related diseases and mortality, in this study, our goal was to investigate the inhibition of nicotine metabolism by P450 2A6. Smoking is the main cause of many diseases and disabilities and harms nearly every organ of the body. As reported by the Centers for Disease Control and Prevention (CDC), more than 16 million Americans are living with diseases caused by smoking. On average, the life expectancy of a smoker is about 10 years less than a nonsmoker. Smoking cessation can substantially reduce the incidence of smoking-related diseases, including cancer. At least, 70 of the more than 7000 cigarette smoke components, including polycyclic aromatic hydrocarbons, N-nitrosamines, and aromatic amines, are known carcinogens. Nicotine is the compound responsible for the addictive and psychopharmacological effects of tobacco. Cytochrome P450 enzymes are responsible for the phase I metabolism of many tobacco components, including nicotine. Nicotine is mainly metabolized by cytochrome P450s 2A6 and 2A13 to cotinine. This metabolism decreases the amount of available nicotine in the bloodstream, leading to increased smoking behavior and thus exposure to tobacco toxicants and carcinogens. Here, we report the syntheses and P450 2A6 inhibitory activities of a number of new flavone-based esters and acids. Three of the flavone derivatives studied were found to be potent competitive inhibitors of the enzyme. Docking studies were used to determine the possible mechanisms of the activity of these inhibitors.

Особенности полового самосознания у больных с органическим расстройством личности и множественными расстройствами сексуального предпочтения

&lt;p style="text-align: justify;"&gt;The article analyzes the results of an empirical study aimed at assessing the dynamics of the parameters of sexual self-awareness and the tendency to aggressive behavior in interpersonal interaction in persons suffering from organic personality disorder with multiple disorders of sexual preference in the process of compulsory treatment. 30 patients were examined before and after the course of treatment (psychopharmacological effects in combination with antiandrogens and cognitive-behavioral psychotherapy). The following methods were used: &amp;ldquo;MyF&amp;rdquo;, &amp;ldquo;CTO&amp;rdquo;, &amp;ldquo;Coding&amp;rdquo;, the &amp;ldquo;Hands&amp;rdquo; test of Wagner. The changes in the psychological characteristics and parameters of sexual self-consciousness revealed in the course of the study allowed us to identify actual targets for psychotherapeutic influence and were taken into account by us when determining the assessment of the risk of relapse and the degree of social danger of patients.&lt;/p&gt;

Novel Psychopharmacological Herbs Relieve Behavioral Abnormalities and Hippocampal Dysfunctions in an Animal Model of Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is an anxiety disorder caused by traumatic or frightening events, with intensified anxiety, fear memories, and cognitive impairment caused by a dysfunctional hippocampus. Owing to its complex phenotype, currently prescribed treatments for PTSD are limited. This study investigated the psychopharmacological effects of novel COMBINATION herbal medicines on the hippocampus of a PTSD murine model induced by combining single prolonged stress (SPS) and foot shock (FS). We designed a novel herbal formula extract (HFE) from Chaenomeles sinensis, Glycyrrhiza uralensis, and Atractylodes macrocephala. SPS+FS mice were administered HFE (500 and 1000 mg/kg) once daily for 14 days. The effects of HFE of HFE on the hippocampus were analyzed using behavioral tests, immunostaining, Golgi staining, and Western blotting. HFE alleviated anxiety-like behavior and fear response, improved short-term memory, and restored hippocampal dysfunction, including hippocampal neurogenesis alteration and aberrant migration and hyperactivation of dentate granule cells in SPS+FS mice. HFE increased phosphorylation of the Kv4.2 potassium channel, extracellular signal-regulated kinase, and cAMP response element-binding protein, which were reduced in the hippocampus of SPS+FS mice. Therefore, our study suggests HFE as a potential therapeutic drug for PTSD by improving behavioral impairment and hippocampal dysfunction and regulating Kv4.2 potassium channel-related pathways in the hippocampus.

Food Discipline According to Ayurveda- A Holistic Approach in Eating Healthy Food with Ayurveda Siddhant Mentioned in Ayurveda and Food Technology

The high end of medical science is the preservation of health and it can be attained in two ways, first of all by eradicating the diseases, which may invade the body, secondly by due observation of such rules as would keep away the disease.Ayurveda elaborate about different dietary regimens including recopies advocated for health promotion, prevention of illness and also prescribed for management of diseases as well which further provide a great scope for the development of nutraceuticals and dietary supplements. Rasayanas are the foods, therapies or practices that are conducive and beneficial to body tissues and its functions. Diet plays an important role in keeping our mind healthy and explicit psycho-pharmacological effects of food led to classification of food in to following 3 categories. 1. Satvik diet: ideal diet containing vegetarian, non-oily, non-spicy articles which are congenial to the body and mind. 2. Rajasik diet: too spicy, hot, sour, salty; excite the mental faculties.3. Tamsik diet: too oily and heavy food. But in the age of systems biology, personalised medicine, and the wider context of a more holistic transition in sciences generally, modern knowledge is reinventing and advancing a number of these ideas. Transdisciplinary study could be important for advancing the fields of food and health sciences as well as for offering real-world remedies for current health issues. This article highlights the need for a deeper engagement with traditional knowledge systems, such as Ayurveda, by quickly reviewing the similarities between Ayurveda and Technology.

Role of Oxidative Stress and Inflammation in Insomnia Sleep Disorder and Cardiovascular Diseases: Herbal Antioxidants and Anti-inflammatory Coupled with Insomnia Detection using Machine Learning.

Insomnia is well-known as trouble in sleeping and enormously influences human life due to the shortage of sleep. Reactive Oxygen Species (ROS) accrue in neurons during the waking state, and sleep has a defensive role against oxidative damage and dissipates ROS in the brain. In contrast, insomnia is the source of inequity between ROS generation and removal by an endogenous antioxidant defense system. The relationship between insomnia, depression, and anxiety disorders damages the cardiovascular systems' immune mechanisms and functions. Traditionally, polysomnography is used in the diagnosis of insomnia. This technique is complex, with a long time overhead. In this work, we have proposed a novel machine learning-based automatic detection system using the R-R intervals extracted from a single-lead electrocardiograph (ECG). Additionally, we aimed to explore the role of oxidative stress and inflammation in sleeping disorders and cardiovascular diseases, antioxidants' effects, and the psychopharmacological effect of herbal medicine. This work has been carried out in steps, which include collecting the ECG signal for normal and insomnia subjects, analyzing the signal, and finally, automatic classification. We used two approaches, including subjects (normal and insomnia), two sleep stages, i.e., wake and rapid eye movement, and three Machine Learning (ML)-based classifiers to complete the classification. A total number of 3000 ECG segments were collected from 18 subjects. Furthermore, using the theranostics approach, the role of mitochondrial dysfunction causing oxidative stress and inflammatory response in insomnia and cardiovascular diseases was explored. The data from various databases on the mechanism of action of different herbal medicines in insomnia and cardiovascular diseases with antioxidant and antidepressant activities were also retrieved. Random Forest (RF) classifier has shown the highest accuracy (subjects: 87.10% and sleep stage: 88.30%) compared to the Decision Tree (DT) and Support Vector Machine (SVM). The results revealed that the suggested method could perform well in classifying the subjects and sleep stages. Additionally, a random forest machine learning-based classifier could be helpful in the clinical discovery of sleep complications, including insomnia. The evidence retrieved from the databases showed that herbal medicine contains numerous phytochemical bioactives and has multimodal cellular mechanisms of action, viz., antioxidant, anti-inflammatory, vasorelaxant, detoxifier, antidepressant, anxiolytic, and cell-rejuvenator properties. Other herbal medicines have a GABA-A receptor agonist effect. Hence, we recommend that the theranostics approach has potential and can be adopted for future research to improve the quality of life of humans.

LC-MS/MS determination of GTS-201, a dipeptide mimetic of the brain-derived neurotrophic factor, and neurotransmitter metabolites with application to a pharmacokinetic study in rats

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family with diverse psychopharmacological effects including antidepressant and anxiolytic actions. However, the clinical use of BDNF is limited due to its poor pharmacokinetic properties. The development of low-molecular-weight BDNF mimetics passing through the blood-brain barrier is an emerging strategy for improved managing psychiatric diseases. The present study characterizes a novel dipeptide mimetic of the 2nd BDNF loop named GTS-201, which exhibits psychotropic properties in experimental animal models of anxiety and alcohol dependence. The aim of this work was to study the pharmacokinetics of GTS-201 in rats at a saturating dosage of 5 mg/kg applied by the intraperitoneal route and to characterize the effects on neurotransmitter levels in the blood and brain. The maximum concentration (Cmax) of GTS-201 in the plasma (867 ± 69 ng/ml) was recorded at 35 ± 7.7 min after administration (Tmax) with a half-elimination period (T1/2) of 19.5 ± 1.8 min, while in the brain tissue Cmax was 14.92 ± 3.11 ng/ml, Tmax was 40.0 ± 7.7 min and T1/2 were 87.5 ± 12.7 min. The relative tissue availability of the GTS-201 for the brain reached 2.9%. At the dose applied, GTS-201 induced a significant increase of serotonin (5-fold) and dopamine levels in the brain tissue (8-fold) along with a decrease in cortisol content in blood plasma 45 min after acute administration. In summary, GTS-201 crosses the blood-brain barrier after acute administration and affects the activity of serotonergic and dopaminergic systems, which may underlie its neuropsychotropic effects described previously.

Synthesis and study of psychotropic activity spectrum of 4-aryl-2-benzoylmethylenehydrazono-4-oxobutanoic acids

Objective. To study psychotropic activity of 4-aryl-2-benzoylmethylenhidrazono-4-oxobutanoic acids, as well as to determine the relationship between the structure of substances and their biological activity.&#x0D; Materials and methods. The spectrum of psychotropic activity of 4-aryl-2-benzoylmethylenehydrazono-4-oxobutanoic acids was studied on experimental animals using the open field, black-and-white camera, and extrapolation deliverance tests.&#x0D; Results. Psychopharmacological effects of various severity and direction were revealed. Two compounds showed anxiogenic properties without deterioration in cognitive potential, one substance displayed a trend to anxiolytic activity. The effect of the certain radicals in the structure of the substances on the studied activities was found.&#x0D; Conclusions. The obtained links between the structure of original compounds and their psychotropic action can be used in further targeted synthesis and search for new domestic pharmaceutical substances with investigated effects in a series of derivatives of 2,4-dioxobutanoic acids.

Psychopharmacological Effects of Stimulation of the Functions of Neural Stem Cells by STAT3 Inhibitor under Conditions of Modeled Ethanol-Induced Encephalopathy.

The psychopharmacological effects of a stimulator of functions of progenitor cells of the nervous tissue STAT3 inhibitor (STAT3 Inhibitor XIV, LLL12) were studied under conditions of modeled alcoholic encephalopathy in C57BL/6 mice. The pharmacological agent corrected the parameters of exploratory behavior (characterizing predominantly cognitive activity) in the experimental animals at the late terms of observation. At the same time, the reproducibility of the conditioned passive avoidance response developed at the beginning of the course STAT3 inhibitor administration decreased. These effects developed against the background of a significant increase in the content of neural stem cells and their proliferative activity in the paraventricular zone of the brain.

Acute Toxicity Studies and Psychopharmacological Effects of Eucalyptus globulus Leaf Oil in Rodents

Acute Toxicity Studies and Psychopharmacological Effects of Eucalyptus globulus Leaf Oil in Rodents

Entactogens: How the Name for a Novel Class of Psychoactive Agents Originated.

At first glance, it appears there is little difference between the molecular structures of methylenedioxymethamphetamine (MDMA), which has an N-methyl attached to its amino group, and methylenedioxyamphetamine (MDA), a primary amine that is recognized to have hallucinogenic activity. It is known from studies with other hallucinogenic amphetamines that N-methylation of hallucinogenic amphetamines attenuates or abolishes hallucinogenic activity. Nevertheless, MDMA is biologically active and has a potency only slightly less than its MDA parent. Importantly, it is the Ievo-isomer of hallucinogenic phenethylamines that is more biologically active, whereas it is the dextro isomer of MDMA that is more active. This reversal of stereochemistry for the activity of two very closely related molecules is a very powerful clue that their mechanisms of action differ. Finally, extension of the alpha-methyl of hallucinogenic amphetamines to an alpha-ethyl moiety completely abolishes their hallucinogenic activity. Ultimately, we extended the alpha-methyl group of MDMA to an alpha-ethyl to afford a molecule we named (N-Methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB) that retained significant MDMA-like psychoactivity. Hence, there are three structural features that distinguish MDMA from the hallucinogenic amphetamines: (1) the N-methyl on the basic nitrogen, (2) the reversal of stereochemistry and, (3) tolerance of an alpha-ethyl moiety as contrasted with the alpha-methyl of hallucinogenic phenethylamines. Clearly, MDMA is distinct from classical hallucinogenic phenethylamines in its structure, and its psychopharmacology is also unique. Thus, in 1986 I proposed the name “Entactogen” for the pharmacological class of drugs that includes 3,4-methylenedioxymethamphetamine (MDMA) and other substances with a similar psychopharmacological effect. The name is derived from roots that indicate that entactogens produce a “touching within.” Rather than having significant psychostimulant, or hallucinogenic effects, MDMA powerfully promotes affiliative social behavior, has acute anxiolytic effects, and can lead to profound states of introspection and personal reflection. Its mechanism of action is now established as involving transport of MDMA by the neuronal serotonin reuptake carrier followed by carrier-mediated release of stored neuronal serotonin.

Acute cannabidiol treatment attenuates ethanol-induced place preference and reduces aggressivity in group-housed male rats

Alcohol abuse is a widespread cause of aggressive and impulsive behaviors that impact the users as well as their entourage. However, only a few medications are effective. Recently, cannabidiol has been reported to improve mood disorders and recovery from substance abuse, yet the psychopharmacologic effects of cannabidiol in ethanol-induced drug reward and aggressivity remain unexplored. In the present study, we investigated the effects of cannabidiol on ethanol-induced place preference and aggressivity in individually and group-housed male rats using the conditioned place preference test, and intruder evoc aggression test, respectively. The obtained results showed that ethanol significantly increased locomotor activity, induced conditioned place preference in all animals, and, specifically, increased aggressivity in individually housed rats. These behavioural impairments induced by ethanol were associated with decreased glucocorticoid and mineralocorticoid receptors transcription in the prefrontal cortex. Notwithstanding, cannabidiol at a dose of 10 mg/kg significantly inhibited Et-OH-induced place preference in group-housed, but not in individually housed rats, and markedly inhibited the aggressive behaviour. These findings suggest that ethanol-induced behavioural impairments are dependent on the housing condition that may affect corticosterone receptors expression and subsequently the animal responsivity to cannabidiol treatment.

Retina photosensitivity indexes as an objective indicator of expression of psychostimulating effect

BACKGROUND: The variety of neurotransmitter systems providing photoreceptor capabilities of the retina is a prerequisite for studying the retinotropic properties of some psychotropic drugs, taking into account their ability to interfere with the work of synapses.&#x0D; MATERIALS AND METHODS: Given this circumstance, a set of studies was carried out with the participation of volunteers to assess the effect of psychotropic substances with a stimulating (caffeine, piracetam, Bilobil) type of action on the functional state of the retina, recorded by the campimetric method. In the course of the research, the photosensitivity of the retina, its ability to distinguish colors and the speed of the visual-motor reaction were assessed. Such an approach can not only demonstrate the interest of retinal cellular elements in the action of substances, but also broaden the question of the participation of the visual system in the psychopharmacological effect.&#x0D; RESULTS: The function of the retina was studied both in healthy volunteers and in individuals with organic lesions of the central nervous system, which were often accompanied by emotional disorders, which were identified using special questionnaire tests. It was found that these pathological conditions are accompanied by a limitation of the photosensitivity of the retina of varying severity. These facts can be interpreted in different ways. On the one hand, violations of visual functions can lead to psychoemotional disorders and be a pathogenetic link in their development, and on the other hand, primary disorders of retinal light and color sensitivity can provoke the development of psychopathology. However, regardless of the pharmacological characteristics of the studied drugs that stimulate mental activity, the relationship of their effect with changes in visual function seems obvious, which makes it possible to raise the question of the advisability of taking into account the light and color sensitivity of the retina for a comprehensive assessment of both the mental state and the pharmacodynamics of the drugs, stimulating mental activity.&#x0D; CONCLUSION: Thus, it is legitimate to conclude that taking into account the light and color sensitivity of the retina can be one of the quantitative criteria for the severity and effectiveness of psychopharmacotherapy.