Psychotropic Effects Research Articles

Discrimination of legal and illegal Cannabis spp. according to European legislation using near infrared spectroscopy and chemometrics.

Aerial parts containing cannabidiol can be purchased in a legal way but cannabis used as recreational drug is illegal in most European countries. Δ9-tetrahydrocannabinol is one of the main cannabinoids responsible for the psychotropic effect. European Union countries and Switzerland authorize a concentration of THC of 0.2 % and 1.0 % w/w, respectively, for smoking products and industrial hemp. Public health inspectors and law enforcement officers need to check the legality of samples. Therefore there is a need for innovative approaches, allowing quality control of these products in an easy way and preferably on site. In many countries, cultivation of industrial hemp is permitted if the THC content does not exceed 0.2 % w/w. A portable equipment could be a useful measuring tool for farmers to check for the THC content at regular time. In this work, 189 samples were analysed with a benchtop and a handheld NIR device in order to create two classification methods according to European and Swiss laws. All samples were also analysed by GC-FID to determine their THC concentration. Supervised analysis was applied in order to establish the best model. For the first classification, the accuracy was 91% for the test set with the benchtop data and 93 % for the test set with the handheld data. For the second classification, the accuracies were respectively 91 % and 95 %. The obtained models, hyphenating spectroscopic techniques and chemometrics, enable to discriminate legal and illegal cannabis samples according to European and Swiss laws.

THC and CBD produce divergent effects on perception and panic behaviours via distinct cortical molecular pathways

Clinical and pre-clinical evidence demonstrates divergent psychotropic effects of THC vs. CBD. While THC can induce perceptual distortions and anxiogenic effects, CBD displays antipsychotic and anxiolytic properties. A key brain region responsible for regulation of cognition and affect, the medial prefrontal cortex (PFC), is strongly modulated by cannabinoids, suggesting that these dissociable THC/CBD-dependent effects may involve functional and molecular interplay within the PFC. The primary aim of this study was to investigate potential interactions and molecular substrates involved in PFC-mediated effects of THC and CBD on differential cognitive and affective behavioural processing. Male Sprague Dawley rats received intra-PFC microinfusions of THC, CBD or their combination, and tested in the latent inhibition paradigm, spontaneous oddity discrimination test, elevated T-maze and open field. To identify local, drug-induced molecular modulation in the PFC, PFC samples were collected and processed with Western Blotting. Intra-PFC THC induced strong panic-like responses that were counteracted with CBD. In contrast, CBD did not affect panic-like behaviours but blocked formation of associative fear memories and impaired latent inhibition and oddity discrimination performance. Interestingly, these CBD effects were dependent upon 5-HT1A receptor transmission but not influenced by THC co-administration. Moreover, THC induced robust phosphorylation of ERK1/2 that was prevented by CBD, while CBD decreased phosphorylation of p70S6K, independently of THC. These results suggest that intra-PFC infusion of THC promotes panic-like behaviour associated with increased ERK1/2 phosphorylation. In contrast, CBD impairs perceptive functions and latent inhibition via activation of 5-HT1A receptors and reduced phosphorylation of p70S6K.

Characteristic patterns of EEG oscillations in sheep (Ovis aries) induced by ketamine may explain the psychotropic effects seen in humans

Ketamine is a valuable anaesthetic and analgesic that in recent years has gained notoriety as a recreational drug. Recently, ketamine has also been proposed as a novel treatment for depression and post-traumatic stress disorder. Beyond its anaesthetic actions, however, the effects of ketamine on brain activity have rarely been probed. Here we examined the cortical electroencephalography (EEG) response to ketamine of 12 sheep. Following ketamine administration, EEG changes were immediate and widespread, affecting the full extent of the EEG frequency spectrum measured (0–125 Hz). After recovery from sedation during which low frequency activity dominated, the EEG was characterised by short periods (2–3 s) of alternating low (<14 Hz) and high (>35 Hz) frequency oscillation. This alternating EEG rhythm phase is likely to underlie the dissociative actions of ketamine, since it is during this phase that ketamine users report hallucinations. At the highest intravenous dose used (24 mg/kg), in 5/6 sheep we observed a novel effect of ketamine, namely the complete cessation of cortical EEG activity. This persisted for up to several minutes, after which cortical activity resumed. This phenomenon is likely to explain the ‘k-hole’, a state of oblivion likened to a near death experience that is keenly sought by ketamine abusers.

Conversion of Cannabidiol (CBD) into Psychotropic Cannabinoids Including Tetrahydrocannabinol (THC): A Controversy in the Scientific Literature.

Cannabidiol (CBD) is a naturally occurring, non-psychotropic cannabinoid of the hemp plant Cannabis sativa L. and has been known to induce several physiological and pharmacological effects. While CBD is approved as a medicinal product subject to prescription, it is also widely sold over the counter (OTC) in the form of food supplements, cosmetics and electronic cigarette liquids. However, regulatory difficulties arise from its origin being a narcotic plant or its status as an unapproved novel food ingredient. Regarding the consumer safety of these OTC products, the question whether or not CBD might be degraded into psychotropic cannabinoids, most prominently tetrahydrocannabinol (THC), under in vivo conditions initiated an ongoing scientific debate. This feature review aims to summarize the current knowledge of CBD degradation processes, specifically the results of in vitro and in vivo studies. Additionally, the literature on psychotropic effects of cannabinoids was carefully studied with a focus on the degradants and metabolites of CBD, but data were found to be sparse. While the literature is contradictory, most studies suggest that CBD is not converted to psychotropic THC under in vivo conditions. Nevertheless, it is certain that CBD degrades to psychotropic products in acidic environments. Hence, the storage stability of commercial formulations requires more attention in the future.

Cannabinoids-Promising Antimicrobial Drugs orIntoxicants with Benefits?

Novel antimicrobial drugs are urgently needed to counteract the increasing occurrence of bacterial resistance. Extracts of Cannabis sativa have been used for the treatment of several diseases since ancient times. However, its phytocannabinoid constituents are predominantly associated with psychotropic effects and medical applications far beyond the treatment of infections. It has been demonstrated that several cannabinoids show potent antimicrobial activity against primarily Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). As first in vivo efficacy has been demonstrated recently, it is time to discuss whether cannabinoids are promising antimicrobial drug candidates or overhyped intoxicants with benefits.

0233 Pain, Fatigue, and Altered Reactivity to a Repeated Physiological Stressor in Insomnia Patients: An Explanatory-Driven Analysis

Abstract Introduction Fatigue and pain are prominent features of functional impairment in insomnia. This study aimed to better understand behavioral and physiological mechanisms of these complex relationships. Methods 22 participants with insomnia disorder (DSM-5 criteria, 18 female, age 18-49yrs) and 22 good-sleeper controls (19 female, age 18-47yrs) completed two-weeks sleep logs and actigraphy recordings prior to coming to the laboratory for overnight polysomnography and subsequent daytime testing that included questionnaires, three trials of cold pressor test (CPT), and pain testing with blood draws collected throughout. Insomnia diagnosis was determined by a board-certified sleep specialist, and exclusion criteria included psychiatric history within past 6 months, other sleep disorder, significant medical conditions, and any medications within past two weeks with significant effects on inflammation, autonomic function, or other psychotropic effects. For CPT, participants were instructed to immerse hand in ice cold water for at least one minute and rate pain intensity throughout the immersion and 3-minute recovery. Data were analyzed with linear mixed models. Results Per inclusion criteria, PSQI scores were differed between groups (insomnia: 10.2±2.7, range 7–16; control: 1.9±1.3, range 0–5; p&amp;lt;.001). Insomnia consistently reported higher daily fatigue ratings compared to controls (p&amp;lt;.001), as well as higher spontaneous pain globally and across several specific domains (p’s: .007-.03). In response to CPT, groups did not differ in their initial tolerance (i.e. immersion duration, p=.41) or intensity ratings during immersion (p=.88), however insomnia showed blunted recovery in intensity ratings (p&amp;lt;.01). Control participants then showed an ability to habituate to repeated CPT by increasing immersion duration, whereas insomnia slightly decreased in tolerance across trials (Group effect: p&amp;lt;.05). Conclusion These data indicate that habituation to and acute recovery from pain is deteriorated in chronic insomnia, which may be a key contributor to maintained pathophysiology over time and mechanism to target with comprehensive treatment. Support Merck Inc. MISP# 51971 (investigator-initiated), NIH/National Center for Research Resources UL1-RR02758 and M01-RR01032 to the Harvard Clinical and Translational Science Center.

Separation of enantiomers and positional isomers of novel psychoactive substances in solid samples by chromatographic and electrophoretic techniques – A selective review

Novel Psychoactive Substances (NPS) represent an alternative to established illicit drugs. They are traded via the internet and exhibit small alterations in their chemical structure to circumvent law, however, their psychotropic effects are comparable. There is still poor knowledge about side effects and health risks. By the end of 2018, 730 NPS were reported to EMCDDA (European Monitoring Centre for Drugs and Drug Addiction). Among different compound classes, many NPS are chiral and few publications deal with the different pharmacological and toxicological properties of their pure enantiomers. Therefore, analytical method development concerning enantioseparation of NPS is of great interest. Chiral separation protocols of established illicit drugs have been transferred for NPS, selected examples are given as well. Different methods for enantioseparation of NPS comprising mainly stimulating drugs such as cathinones, pyrovalerones, amphetamines, ketamines, (2-aminopropyl) benzofuranes, phenidines, phenidates, morpholines and thiophenes are reviewed. Moreover, chiral resolution of some cannabinomimetics by HPLC is presented. Chromatographic and electrophoretic techniques such as GC, HPLC, SFC, CE and CEC are discussed and in some cases compared. Mainly, solid samples either purchased from internet vendors, seized by police or collected from patients in hospitals are subject to analysis. Chiral selectors used for HPLC are listed in a Table. It was shown that particularly stimulating drugs are traded as racemic mixtures, which is not the case with cannabinomimetics. Mainly, HPLC and CE were used for enantioseparation of NPS.

Behavioral effects of new compounds based on coumarin in rats

Introduction. A study of the effects of coumarins has not received widespread use in medicine, largely due to the lack of optimal dosage forms, the creation of which is complicated by their poor solubility in water. Currently, studies are underway on the synthesis of macromolecules, combining various structural fragments, which will lead to increased biological activity of the synthesized coumarin derivatives compared to natural coumarins.&#x0D; The aim of this work was to study the central effect of new coumarin-based compounds: IEM-2262, IEM-2263, IEM-2266, IEM-2267 on emotional and research behavior in rats.&#x0D; Methods. Studies have been carried out using battery of tests that are commonly used to study emotional and exploratory behavior: an open field test and an elevated plus maze in rats. The neuroprotector mexidol (200 mg/kg i.p., Farmasoft, Russia) was used as a reference substance.&#x0D; Results. Coumarins (1050 mg/kg ip) have been shown to have a mild psychotropic, predominantly anti-anxiety and sedative effect. 7-Alkoxycoumarins (IEM-2262 and IEM-2266) and 4-aminocoumarins (IEM-2263 and IEM-2267) have different sensitivity in the open field compared with the effects in the elevated plus maze. Anxiolytic properties appeared in the elevated plus maze after the administration of 4-aminocoumarins (IEM-2263 and IEM-2267). The number of defecation boluses in the open field decreased as a result of the administration of 7-alkoxycoumarins (IEM-2262), which was associated not only with fear of novelty, but to a greater extent with anti-stress action. Thus, the new coumarin derivatives have mild tranquilizing and anti-stress effects and can be used in the future for post-traumatic stress disorders with panic attacks.

A single administration of the antibiotic, minocycline, reduces fear processing and improves implicit learning in healthy volunteers: analysis of the serum metabolome

Minocycline has shown therapeutic promise in pre-clinical animal models and early phase clinical trials for a variety of psychiatric disorders. Previous studies on minocycline have shown its ability to suppress microglia activity and reduce inflammatory cytokine levels, and its amelioration of depressive-like behaviour in animals and humans. However, the underlying mechanisms that lead to minocycline’s psychotropic effects are not clear. In this study, we investigated the psychological and biochemical effects of an acute dose of minocycline or placebo in 40 healthy adult volunteers. Psychological changes in emotional processing, implicit learning, and working memory were assessed. Plasma inflammatory markers, measured with enzyme-linked immunosorbent assays, and serum metabolites, measured with proton nuclear magnetic resonance combined with multi-variate analysis techniques, were also studied. Results showed that minocycline administration decreased fear misclassification and increased contextual learning, which suggested that reducing negative biases and improving cognition, respectively, may underlie the antidepressant actions of this agent. An examination of serum metabolites revealed higher levels of lipoproteins, particularly cholesterol, in the minocycline group. Minocycline also decreased circulating concentrations of the inflammatory marker C-Reactive Peptide, which is consistent with previous research. These effects highlight two important psychological mechanisms that may be relevant to the efficacy of minocycline reported in clinical trials, and also suggest a possible largely unexplored lipid-related biochemical pathway for the action of this drug.

Cocaine Receptor Identified as BASP1

Cocaine exerts its behavioral actions mainly through inhibition of dopamine reuptake. However, cocaine is a weak and non-selective inhibitor of the monoamine transporters. In addition, many dopamine reuptake inhibitors do not produce psychotropic effects in drug-experienced volunteers. On the other hand, previous evidence indicates more potent effects of cocaine. For example, low nanomolar cocaine regulates dopamine D2 receptor signaling. In planarians, low nanomolar levels of cocaine produces environmental place conditioning. These signaling and behavioral actions of cocaine could not be mediated through the inhibition of monoamine transporters. Furthermore, previous a study describes 16 nM cocaine binding in rat striatal synaptosomes suggesting the existence of a high-affinity receptor for cocaine. However, the identity of such receptor is unknown.

Computational aided acetaminophen – phthalic acid molecularly imprinted polymer design for analytical determination of known and new developed recreational drugs

In recent times, abuse drug consumption rates have been increasing. In addition, authorities have detected a trend in the development of new substances expressly created to avoid legislation. These novel psychoactive substances (NPS) are non-registered formulations, closely chemically related to outlawed ones to maintain the same psychotropic effects while circumventing legal restrictions.This issue arises enormous social, sanitary, and road safety problems since there is no way to detect nor quantify these non-registered substances.The aim of this work is the development of a high selective material able to pre-concentrate and detect NPS. On that account, molecularly imprinted polymers (MIPs) designed with an imprinted cavity that matches the cathinones structural shape were proposed to detect both conventional and new cathinone derived recreational drugs.The increasing number of illicit drug modifications that is being reported requires developing a receptor valid for not only known molecules but also for incoming ones; thus, a virtual procedure must be carried out to take a step forward towards future modifications. Accordingly, a computational MIP design is proposed as the most appropriated method to effectively design this receptor.By means of molecular dynamics and molecular docking, several combinations are studied regarding their pre-polymerization complex stability but also their rebinding capacity against the proposed analytes.Hence, a phthalic acid – acetaminophen MIP is selected as the most well-suited receptor, valid for current and forthcoming cathinone recreational drugs.

Can Hemp Help? Low-THC Cannabis and Non-THC Cannabinoids for the Treatment of Cancer.

Cannabis has been used to relieve the symptoms of disease for thousands of years. However, social and political biases have limited effective interrogation of the potential benefits of cannabis and polarised public opinion. Further, the medicinal and clinical utility of cannabis is limited by the psychotropic side effects of ∆9-tetrahydrocannabinol (∆9-THC). Evidence is emerging for the therapeutic benefits of cannabis in the treatment of neurological and neurodegenerative diseases, with potential efficacy as an analgesic and antiemetic for the management of cancer-related pain and treatment-related nausea and vomiting, respectively. An increasing number of preclinical studies have established that ∆9-THC can inhibit the growth and proliferation of cancerous cells through the modulation of cannabinoid receptors (CB1R and CB2R), but clinical confirmation remains lacking. In parallel, the anti-cancer properties of non-THC cannabinoids, such as cannabidiol (CBD), are linked to the modulation of non-CB1R/CB2R G-protein-coupled receptors, neurotransmitter receptors, and ligand-regulated transcription factors, which together modulate oncogenic signalling and redox homeostasis. Additional evidence has also demonstrated the anti-inflammatory properties of cannabinoids, and this may prove relevant in the context of peritumoural oedema and the tumour immune microenvironment. This review aims to document the emerging mechanisms of anti-cancer actions of non-THC cannabinoids.

Methylone screening with electropolymerized molecularly imprinted polymer on screen-printed electrodes

Methylone (also known as bk-MDMA) is a substituted cathinone developed to elicit similar psychotropic effects as 4-methylenedioxymethamphetamine (MDMA, also known as ecstasy). Although methylone is a scheduled substance, its specific structural features means it generally cannot be detected and quantified using the same conditions commonly employed for ecstasy. This work therefore describes the development of an electroanalytical method for the selective quantification of methylone. This method uses an electropolymerized molecularly imprinted polymer (MIP) on the surface of screen-printed gold electrodes (SPAuEs), using 2-mercaptobenzimidazole (2-MBI) as the building monomer and methylone as the analyte template. The construction and optimization of the SPAuE-MIP sensor was studied, step-by-step, using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Additionally, the direct electrooxidation of methylone was investigated, and methylone-MIP interactions probed computationally. Ultimately, square-wave voltammetry (SWV) quantification of methylone using the SPAuE-MIP sensor was demonstrated to be both sensitive and selective. The electroanalytical determination showed suitable analytical parameters as: intra-day repeatability of 1.5%, a limit of detection (LOD) of 1.1 μmol L−1 (0.23 mg L−1) and a linear range up to 50 μmol L−1 (ca. 10 mg dL−1) with an r2 of 0.996, as well as much higher currents towards the analyte than similar compounds and commonly present interferents.

Phytochemical and histochemical studies on Solanum diphyllum L.- An exotic potent weed

Plant-based substances are seeking attention due to their substantial medical benefits. Medicinally, as well as in terms of poisoning and psychotropic effects, members of the family Solanaceae have been of great importance and used throughout history. The present study mainly focuses on the identification and location ofan important exotic plant speciesSolanumdiphyllum L. proven to be a potentially fast-spreading weed being reported from various states of South India and the detection of important biologically active chemical compounds in the same to look into the discovery of new herbal formulations and their curative properties for treatment of common ailments.

Occupational Exposure to Secondhand Cannabis Smoke Among Law Enforcement Officers Providing Security at Outdoor Concert Events.

Numerous states within the USA have legalized cannabis for medical or non-medical (adult/recreational) use. With the increased availability and use of cannabis, occupational and environmental exposures to secondhand cannabis smoke (SHCS) raise concerns over whether non-users may be at risk for a 'contact high', impaired neurocognitive function, harm from irritants and carcinogens in smoke, or potentially failing a cannabis screening test. The extent of health effects from potential occupational exposure to SHCS is unknown. This is a study of occupational exposures to SHCS among law enforcement officers (LEOs) providing security at outdoor concerts on a college campus in a state where adult use of cannabis is legal. Investigators evaluated a convenience sample of LEOs' potential exposure to SHCS and symptoms experienced while providing security during two open-air stadium rock-n-roll concerts on consecutive days in July 2018. During each event, full-shift area and LEO personal air samples were collected for Δ9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of cannabis. Urine (pre- and postevent; n = 58) and blood (postevent; n = 29) were also collected and analyzed for Δ9-THC and two of its metabolites [11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) and 11-nor-hydroxy-delta-9-tetrahydrocannabinol (OH-THC)]. Urine samples were analyzed using ultrahigh performance liquid chromatography coupled with positive electrospray ionization tandem mass spectrometry and results were compared with the Department of Transportation guidelines for urine screening for cannabis. Blood (postevent) samples were also collected and the plasma fraction was tested for Δ9-THC, THC-COOH, and OH-THC using high-performance liquid chromatography coupled with mass spectrometry. LEOs also completed a medical questionnaire asking about symptoms experienced during the concerts. Twenty-nine LEOs participated in the evaluation. Measurable amounts of Δ9-THC were found in area (concentrations ranged from non-detectable to 330 ng m-3) and personal air samples (53-480 ng m-3). Small amounts (<1.0 ng ml-1) of a Δ9-THC metabolite (THC-COOH) were found in the postevent urine of 34% of LEOs. Neither Δ9-THC nor its metabolites were detected in any blood sample. LEOs reported experiencing non-specific symptoms during the concerts, such as burning, itchy, or red eyes (31%); dry mouth (21%); headache (21%); and coughing (21%). Identification of Δ9-THC in the breathing zone for some LEOs indicates the potential for airborne exposure to the psychoactive component of cannabis. However, the magnitude of these exposures was small compared with those that would result in a dose of Δ9-THC associated with psychotropic effects. Similarly, THC-COOH was found in the postevent urine of some LEOs at concentrations that were orders of magnitude below active use cut-points used during a cannabis screening test (50 ng ml-1). Exposure to SHCS was not high enough to detect concentrations of THC, THC-COOH, to OH-THC in the blood, which could be due to differences between the limits of detection for the tests employed. The ocular and respiratory symptoms reported by LEOs may be related to irritants in SHCS. However, the health effects of SHCS remain unclear, and further research concerning occupational and environmental exposures is warranted.

An evaluation of the anti-hyperalgesic effects of cannabidiolic acid-methyl ester in a preclinical model of peripheral neuropathic pain.

Chronic neuropathic pain (NEP) is associated with growing therapeutic cannabis use. To promote quality of life without psychotropic effects, cannabinoids other than Δ9-tetrahydrocannabidiol, including cannabidiol and its precursor cannabidiolic acid (CBDA), are being evaluated. Due to its instability, CBDA has been understudied, particularly as an anti-nociceptive agent. Adding a methyl ester group (CBDA-ME) significantly enhances its stability, facilitating analyses of its analgesic effects in vivo. This study examines early treatment efficacy of CBDA-ME in a rat model of peripherally induced NEP and evaluates sex as a biological variable. After 14 consecutive days of intraperitoneal CBDA-ME administration at 0.01, 0.1 and 1 μg·kg-1 , commencing 1 day after surgically implanting a sciatic nerve-constricting cuff to induce NEP, the anti-nociceptive efficacy of this cannabinoid was assessed in male and female Sprague-Dawley rats relative to vehicle-treated counterparts. In females, 2 and 4 μg·kg-1 daily doses of CBDA-ME were also evaluated. Behavioural tests were performed for hind paw mechanical and thermal withdrawal thresholds once a week for 8 weeks. At endpoint, in vivo electrophysiological recordings were obtained to characterize soma threshold changes in primary sensory neurons. In males, CBDA-ME elicited a significant concentration-dependent chronic anti-hyperalgesic effect, also influencing both nociceptive and non-nociceptive mechanoreceptors, which were not observed in females at any of the concentrations tested. Initiating treatment of a peripheral nerve injury with CBDA-ME at an early stage post-surgery provides anti-nociception in males, warranting further investigation into potential sexual dimorphisms underlying this response.

A regulatory take on cannabis and cannabinoids for medicinal use in the European Union.

The discovery of the endocannabinoid system has raised public interest in the medicinal use of cannabis, phytocannabinoids, and synthetic cannabinoids, which has always been closely regulated due to their psychotropic effects and potential abuse. The review takes a quick look at the current legal framework in the European Union, which regulates cannabis use and cultivation for medicinal purposes in line with the United Nations Conventions on the production, trade, and use of cannabis, phytocannabinoids, and synthetic cannabinoids. And while the EU legislation precisely defines requirements and marketing authorisation procedures for medicinal products for all EU member states, there is no common regulatory framework for magistral and officinal preparations containing cannabinoids, as they are exempt from marketing authorisation. Instead, their regulation is left to each member state, and it is quite uneven at this point, mainly due to cultural and historical differences between the countries, leading to different access to non-authorised medicinal products. Therefore, to meet great public interest, harmonised approaches on cannabinoid-containing products without marketing authorisation would be welcome to level the playing field in the EU.

Mechanism of Sodium Channel Inhibition by Cannabidiol

The cannabis plant contains over 120 active constituents, collectively known as phytocannabinoids. Among these, some cause psychotropic effects, and others do not. The main non-psychotropic phytocannabinoid is cannabidiol (CBD). CBD has been suggested to be a useful therapeutic compound against a variety of different conditions, including muscle spasms, pain, and seizures. Whereas most reports of CBD efficacy are anecdotal, some have been substantiated in clinical trials. Reports of CBD efficacy, along with its low affinity for CB receptors, have inspired research on targets other than CB1 and CB2 receptors.

Focus sur le système endocannabinoïde et la reprotoxicité du cannabis chez la femme à l’heure du débat sur sa dépénalisation en France

Among recreative compounds, marijuana is the most used worldwide. Delta9THC binding on brain endocannabinoid receptors drives its psychotropic effects. The endocannabinoid system (ECS) is an endogenous neurohormonal system essential for homeostasis composed of ligands, metabolic enzymes and at least 2 receptors discovered to date. In female reproduction, the ECS regulates the hypothalamic-pituitary axis and many steps of the reproduction process, such as ovulation, tubal transportation and trophoblast implantation. Delta9THC can cross the placental barrier and bind to the fetal endocannabinoid system. In humans, fetal and obstetrical consequences of marijuana use during pregnancy are intrauterine growth restriction and preterm delivery. In the light of legalization projects currently reviewed in several western countries, further research should be conducted to improve knowledge on maternal, fetal and reprotoxic consequences of marijuana use during reproductive age and pregnancy.

Psychotropic Effects of a New Pyrazolo[C]Pyridine Derivate GIZh-72 are Related to Functional Activity of Atp-Sensitive Potassium Channels.

We studied the influence of intraperitoneal injection of ATP-sensitive potassium channels inhibitor glibenclamide in doses of 0.01, 0.1, 1, and 10 mg/kg on the effects of a new pyrazolo[C]pyridine derivative GIZh-72 (4,6-dimethyl-2-(4-chlorphenyl)-2,3-dihydro-1Hpyrazolo[ 4,3-C]pyridine-3-on, chloral hydrate; 20 mg/kg, intraperitoneally) in the marble burying and open-field tests in mice. It was found that glibenclamide produced an anxiolytic effect in the open-field test (in a dose of 0.01 mg/kg) and anticompulsive effect in the marble burying test (in doses of 1 and 10 mg/kg). The observed behavioral effects of glibenclamide did not depend on blood glucose level. At the same time, glibenclamide in subeffective (0.01 and 0.1 mg/kg) and effective (1 and 10 mg/kg) doses potentiated the psychotropic effects of GIZh-72 in these tests. It can be assumed that the psychotropic effects of GIZh-72 depend on functional activity of ATP-sensitive potassium channels.