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Official websites use. Share sensitive information only on official, secure websites. E-mail: jk pronexus. The designer drug 1- 4-methylphenyl methylaminopropanone 4-methylmethcathinone, mephedrone is reported to possess psychostimulant, entactogenic and hallucinogenic effects. The purpose of this study was to examine the effects of acute administration of mephedrone on extracellular levels of dopamine DA and 5-HT in the nucleus accumbens of awake rats and compare these effects with those induced by 3,4-methylenedioxymethamphetamine MDMA, ecstasy and amphetamine. Microdialysis sampling was performed while simultaneously recording locomotor activity in rats and the monoamines were determined by HPLC with electrochemical detection. Locomotor activity was increased most by amphetamine, whereas both mephedrone and MDMA showed about three times lower and shorter-lasting effects. The neurochemical and functional properties of mephedrone resemble those of MDMA, but it also shows an amphetamine-like effect in that it evokes a rapid release and elimination of DA in the brain reward system, a feature that may contribute to its potent re-inforcing properties. Keywords: 4-methylmethcathinone; cathinones; phenethylamines; 3,4-methylenedioxymethamphetamine; microdialysis; dopamine; 5-HT; serotonin; legal highs; psychostimulants. Mephedrone 1- 4-methylphenyl methylaminopropanone, 4-methylmethcathinone, 4-MMC is a substituted phenethylamine, structurally a cathinone derivative that possesses powerful psychostimulant, entactogenic and hallucinogenic effects see Europol—EMCDDA, ; Schifano et al. During the last 2 years, mephedrone has been banned in most of the EU countries. However, the unified international legislation and control of mephedrone as a substance of abuse is still missing. The users of mephedrone have described its psychomimetic effects being comparable to amphetamine, cocaine and 3,4-methylenedioxymethamphetamine MDMA, ecstasy causing euphoria, elevated mood, stimulation, enhanced appreciation for music, decreased hostility, improved mental function and mild sexual stimulation Europol—EMCDDA, A recent web-based survey from responders revealed that mephedrone users consider its effects best compared with those of MDMA Carhart-Harris et al. However, mephedrone is associated with a high risk of triggering repetitive and uncontrolled drug intake subsequent to its initial administration. Excessive intake of mephedrone leads to acute intoxication, displaying the clinical features of acute sympathomimetic toxidrome Wood et al. Based on the spectrum of psychostimulant effects described by the drug users and the chemical similarity of mephedrone to substituted methcathinone and methamphetamine it has been speculated that mephedrone may act via increased release and re-uptake inhibition of 5-HT serotonin and dopamine DA Schifano et al. However, there are no data available to provide neurochemical evidence for the in vivo effects of mephedrone on DA and 5-HT transmission in the brain areas implicated in drug reinforcement. Indeed, cathinone was shown to exert similar effects to amphetamine, increasing locomotor activity Kalix, and extracellular DA levels in the nucleus accumbens NAcc and caudate-putamen of rats Pehek et al. Both animal and human studies revealed that the acute re-inforcing effects of drugs, as well as their incentive and reward seeking behaviour, are anatomically linked to the NAcc and mesolimbic DA system see Koob and Volkow, All drugs were dissolved in saline and administered s. Male Sprague-Dawley rats weighing — g were used in the study. The microdialysis experiments were carried out on awake rats following the protocol described elsewhere Kehr, ; Kehr and Yoshitake, All efforts were made to minimize animal suffering and the number of animals used for the study. The middle scalp incision of 2—3 cm was made and the flaps were kept aside using the homeostatic forceps. After exposure of the skull, a hole for a probe and two holes for the fixing screws were drilled using a fine trephine drill. The guide cannula for a microdialysis probe Eicom Corp. The guide cannula was fixed firmly to the skull surface using dental cement. Following 5—7 days of recovery, a microdialysis probe Eicom CX-I; 0. After the initial stabilization period of 2—3 h, the microdialysis samples were collected in 20 min intervals. At the end of the experiment, the animals were killed by an overdose of isoflurane and dislocation of the neck. The brains were removed and examined for correct placement of the probe the probe track in the rat brain. This arrangement allowed for simultaneous recordings of locomotor activity and microdialysis sampling. The data were collected by counting and summarizing the overall activity number of beam crossings in 5 min intervals and further pooled into 20 min bins, thereby matching the frequency of microdialysis sampling. The mobile phase was a mixture of methanol and 0. The chromatograms were recorded and integrated by use of a computerized data acquisition system Clarity DataApex, Prague, Czech Republic. The chromatograms were recorded and integrated by use of the computerized data acquisition system Clarity DataApex. Mean basal levels were compared by use of one-way anova followed by Newman—Keuls multiple comparison test. Differences between the groups of treatment and interaction of treatment and time were analysed by repeated measures two-way repeated measures anova followed by Bonferroni's post-test. A typical placement of the guide cannula and the microdialysis probe in the NAcc is illustrated in Figure 1. As seen, the membrane of the microdialysis probe was positioned preferentially in the NAcc shell but protruded also to the core part of the nucleus. The basal levels of monoamines and metabolites did not significantly differ within the respective treated groups. A representative placement of the microdialysis probe in the nucleus accumbens. The membrane of the microdialysis probe is targeting preferentially the shell but protruded also to the core part of the nucleus. Adapted from Paxinos and Watson Effects of a single s. The arrow indicates the time of drug or vehicle administration. The increased concentrations of DA and 5-HT returned rapidly within the next — min to the basal levels. Following administration of mephedrone at the higher dose, the DOPAC levels were significantly reduced by A similar decrease by The columns represent the AUC 0— min values calculated as the differences in relative changes in DA and 5-HT over a 3 h period between the drug- and vehicle-treated groups. Locomotor activity of vehicle- and drug-treated rats was monitored simultaneously during the microdialysis sampling period Figure 5. The mephedrone-induced motor activation showed a peak level of MDMA caused a similar, not significant motor activation Amphetamine induced a robust and long-lasting locomotor activation with a maximum of The overall value of locomotor activation AUC 0— min by amphetamine was 4. The drug or vehicle was administered at time 0 min arrow. Cathinone derivatives and, in particular, mephedrone has gained wide popularity as a research chemical and a party drug in several European countries see Europol—EMCDDA, including Sweden Gustavsson and Escher, , England Brandt et al. The users of mephedrone have compared its powerful psychostimulant, entactogenic and hallucinogenic properties to other abuse substances of this class including amphetamine, methamphetamine, cocaine and ecstasy Europol—EMCDDA, ; Winstock et al. In a survey among dance drug users in the UK Winstock et al. However, the use of mephedrone is associated with a high risk of overdose, leading to uncontrolled and often fatal drug intoxication Gustavsson and Escher, ; Dickson et al. The major finding of the present study is that mephedrone causes significant, rapid and dose-dependent increases in both 5-HT and DA levels in the NAcc. The overall effects of mephedrone injected at a higher dose on the 5-HT levels were comparable to the effects induced by the same dose of MDMA. In addition, mephedrone but not MDMA, still potently increased the accumbal DA release to a level that was comparable to the effect induced by amphetamine. Amphetamine had only a minor effect on extracellular 5-HT concentrations. The effects of MDMA and amphetamine on the release of DA and 5-HT in the rat NAcc observed in this study are in good agreement with earlier reports on the effects of these two drugs given at similar doses. Thus, a single i. However, in another paper, Kurling et al. Auclair et al. Microdialysis data provide valuable information on the in vivo pharmacodynamics of neurotransmitter release; however, the data do not allow a direct evaluation of a potential mechanism of action of drugs such as mephedrone. Strategies based on increased 5-HT transmission, for example, by use of amphetamine analogues that release both DA and 5-HT Rothman et al. In a recent study, Baumann and colleagues Baumann et al. Although the microdialysis data on DA release in NAcc did not correlate with the in vitro predictions, the authors found good correlations between extracellular DA levels and locomotor activity. The increases in 5-HT release in NAcc were proportional to the decreased DA release and decreased locomotion, the most significant effect was observed for the p-methylamphetamine PAL analogue Baumann et al. These data support the findings in our study, demonstrating that substituted phenethylamines mephedrone and MDMA markedly increase 5-HT release, but lower DA release and reduce locomotor activity when compared with the effects of amphetamine. In this respect, it could be predicted that mephedrone and MDMA are weaker re-inforcers than amphetamine or cocaine. On the other hand, it was reported that some users compulsively redose mephedrone, consuming their whole supply during a session Europol—EMCDDA, This conclusion is in agreement with our data showing that mephedrone, given at a same dose as MDMA, is a more potent DA releaser than MDMA, whereas the elimination rate of mephedrone-induced DA release in the NAcc was almost 10 times faster than that of induced by MDMA and two times faster than that induced by amphetamine. The calculated elimination rates of extracellular DA and 5-HT levels correlate well with the pharmacokinetic profiles of MDMA and amphetamine reported elsewhere. There are no pharmacokinetic data available on mephedrone. Six mephedrone phase I metabolites have been identified in rat urine and seven in human urine Meyer et al. The initial metabolic step for both species is N-demethylation of mephedrone to normephedrone. It is not known whether normephedrone possesses any psychomimetic properties. This possibility cannot be excluded, particularly when considering an analogous N-demethylation of methamphetamine to its active metabolite amphetamine see Schep et al. Here, the rats self-administered at about 0. However, further studies are necessary to demonstrate whether mephedrone can induce self-administration in rats. From a comparison of the time courses of locomotor activation induced by mephedrone, MDMA and amphetamine it was concluded that the overall effect of mephedrone was equipotent to MDMA; however, the mephedrone-induced motor activation diminished about three, and six times faster than that induced by MDMA and amphetamine, respectively. Amphetamine caused a marked increase in locomotor activity that lasted for about min; this finding is in good agreement with data reported elsewhere Cadoni and Di Chiara, ; Kurling et al. On the other hand, the amphetamine-induced locomotion could be almost completely abolished by the blockade of 5-HT 2A receptors in the ventral tegmental area of the rat Auclair et al. These data indicate a complex interplay between NA and 5-HT and their respective receptors in controlling the release of DA in the NAcc induced by various psychostimulant drugs. In conclusion, the present data demonstrate for the first time that acute administration of mephedrone induces a rapid release of both 5-HT and DA in the NAcc of awake rats and this effect is accompanied by a short-lasting increase in locomotor activity. These results support the notion that mephedrone resembles the key neurochemical and functional properties of MDMA, confirming the similarities between mephedrone and MDMA effects reported by drug users. In addition, mephedrone-induced release and rapid elimination of DA in the NAcc were similar to the effect of amphetamine given at a dose relevant to its addictive properties. However, further studies are needed to elucidate the detailed mechanisms behind the reported risk of a compulsive binge intake of mephedrone and the risk for tolerance development. As a library, NLM provides access to scientific literature. Br J Pharmacol. Find articles by J Kehr. Find articles by F Ichinose. Find articles by S Yoshitake. Find articles by M Goiny. Find articles by T Sievertsson. Find articles by F Nyberg. Find articles by T Yoshitake. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.

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Uppsala buying Ecstasy

These datasets underpin the analysis presented in the agency's work. Most data may be viewed interactively on screen and downloaded in Excel format. All countries. Topics A-Z. The content in this section is aimed at anyone involved in planning, implementing or making decisions about health and social responses. Best practice. We have developed a systemic approach that brings together the human networks, processes and scientific tools necessary for collecting, analysing and reporting on the many aspects of the European drugs phenomenon. Explore our wide range of publications, videos and infographics on the drugs problem and how Europe is responding to it. All publications. More events. More news. We are your source of drug-related expertise in Europe. We prepare and share independent, scientifically validated knowledge, alerts and recommendations. About the EUDA. Alongside the more well-known substances available on illicit drug markets, a number of other substances with hallucinogenic, anaesthetic, dissociative or depressant properties are used in Europe: these include LSD lysergic acid diethylamide , hallucinogenic mushrooms, ketamine, GHB gamma-hydroxybutyrate and nitrous oxide. On this page, you can find the latest analysis of the situation regarding these substances in Europe, including seizures, prevalence and patterns of use, treatment entry, harms and more. European Drug Report — home. The drug situation in Europe up to Drug supply, production and precursors. Synthetic stimulants. Heroin and other opioids. Other drugs. New psychoactive substances. Injecting drug use in Europe. Drug-related infectious diseases. Drug-induced deaths. Opioid agonist treatment. Harm reduction. Some of these substances appear to have become well-established in some countries, cities or specific populations, although overall their relative prevalence may remain low in comparison to some other better-known drug classes. However, for a variety of methodological and historical reasons, our current monitoring approaches often perform poorly in identifying patterns and trends in the use of less well-known substances. This makes it difficult to comment with confidence on the prevalence of use or recent trends, or on the extent to which these drugs are associated with health or social problems. The information available suggests, however, that in some countries, subgroups or settings, the use of these sorts of substances has become more common. As patterns of drug use can change rapidly and many of the drug-related problems we face are increasingly influenced by the co-consumption of multiple substances, there is a strong argument for increasing investment in the surveillance of substances with hallucinogenic, anaesthetic, dissociative or depressant properties. The quantity of ketamine seized and reported to the EU Early Warning System on new psychoactive substances has varied over time, but has remained at relatively high levels in recent years, tripling from just under a tonne in to 2. Seizures were reported by 17 countries in both years, with both Denmark and the Netherlands reporting large seizures, and these two countries together accounted for two thirds of the overall quantity of ketamine seized in Most of the ketamine seized in Europe is thought to originate from India, but there is some evidence that the drug may also be sourced from Pakistan and China. Available information suggests that production of the drug in Europe remains limited. Overall, there is evidence to suggest that ketamine is likely to be consistently available in some national drug markets and may have become an established drug of choice in some settings. It is also reported to be used in combination with other substances, such as stimulants. In Ireland, for example, the intentional mixing of cocaine and ketamine has been identified at music festivals, as have ketamine-related medical incidents during and In , Euro-DEN sentinel hospital emergency departments in Europe reported that cocaine was the substance most often reported in combination with ketamine in acute toxicity presentations. Ketamine is commonly snorted, but can also be injected, and has been linked to various dose-dependent acute and chronic harms, including neurological and cardiovascular toxicity, mental health problems, such as depression, and urological complications, such as bladder damage from intensive use or the presence of adulterants. Ketamine may also be added to other drug mixtures, including MDMA powders and tablets, potentially making inadvertent consumption an issue. In contrast to some other parts of the world, mixtures sold as pink cocaine are less likely to contain the synthetic drug 2C-B, which has historically been associated with this product. It is also interesting to note that while the overall figure remains low, both the quantity of 2C-B seized and the number of countries reporting seizures increased in , with 14 countries reporting seizures amounting to just under 6 kilograms of this drug. The number of clients reported to receive treatment for problems related to ketamine use remains low. However, it has risen from around cases reported in to in Moreover, this data set is not likely to capture all those having health problems with this drug. For example, those who have developed urological problems may be poorly represented. Nitrous oxide, commonly known as laughing gas, has been linked to various health problems, including poisonings, burns and lung injuries and, in some cases of prolonged exposure, neurotoxicity from vitamin B12 deficiency. There is, however, a debate on the extent to which this substance is associated with negative health risks, especially among episodic users, although given its apparent growing popularity among young people, this is clearly an important area for further research and monitoring. In some European cities, discarded nitrous oxide gas canisters have become a relatively common sight, and the disposal of the smaller stainless steel canisters has been identified as a drug-litter issue in some countries. The drug has become more accessible and cheaper, available online and with the increased availability of larger gas canisters aimed at recreational use. However, high-volume cylinders may also increase the risk of lung damage, due to the higher pressure of their contents and, in general, inhaling directly from gas bottles is reported to be associated with a greater risk of harm. Nitrous oxide has various commercial uses, for example, it is used by the catering industry. Regulatory approaches to the sale and use of this substance vary between countries, with the gas legally available for sale in some countries. Several EU countries, including Denmark, France, Lithuania, the Netherlands and Portugal have restricted the availability of nitrous oxide in recent years. There is limited evaluative information about the effectiveness of legislative or other approaches to restricting access to nitrous oxide. Non-controlled and new benzodiazepines also continued to be available in some European countries but, again, current monitoring approaches make it difficult to comment on the scale of their use, although signals exist that these substances may have important consequences for health, especially when consumed in combination with other drugs. They are often very cheap and may be used by young people in combination with alcohol, sometimes resulting in potentially serious health reactions or aberrant behaviour. These substances have also been linked to overdose deaths among people who use opioids. A lack of toxicological information means the role that benzodiazepines play in opioid-related deaths is not sufficiently understood. So far, seizures of benzo-dope have been reported by Estonia and Latvia. In both countries, the same mixtures have also been identified in residues analysed from used syringes. Both clinical and public interest has been growing in the therapeutic use of some novel substances, particularly psychedelic substances, but also dissociative drugs such as ketamine. At the same time, a growing number of clinical studies, both internationally and in Europe, are exploring the potential of a range of psychedelic substances to treat different mental health conditions. The evidence base in this area is growing rapidly, and some studies have produced evidence to support the view that some substances may have value in the treatment of specific neuropsychiatric disorders, such as post-traumatic stress disorder or treatment-resistant depression and major depressive disorder. However, the interpretation of the results is complicated by a range of methodological issues, and generalisation remains difficult as much of the research in this area remains at an early stage. Nonetheless, these developments have received considerable media attention, raising concerns that this may encourage greater experimental use of a range of potent psychoactive substances without appropriate medical support, potentially putting vulnerable individuals at risk of suffering adverse consequences. At the same time, there are signs of unregulated programmes being operated in the European Union and elsewhere, in which the use of psychedelic substances is included as part of a wellness, therapeutic or spiritually oriented intervention. Strengthening monitoring in this area will be important, as a growth of unlicensed therapeutic uses of psychedelics may adversely affect vulnerable individuals with pre-existing mental health conditions. Mean daily amounts of ketamine in milligrams per population. Sampling was carried out over a week in March and April For the complete data set and analysis, see Wastewater analysis and drugs — a European multi-city study. Increases were observed in the number of clients entering treatment for problems related to ketamine use in Belgium, Germany and Italy in and Spain in most recent data , with the overall number rising from in to an estimated clients in in these countries. Show source tables. The complete set of source data for the European Drug Report including metadata and methodological notes is available in our data catalogue. A subset of this data, used to generate infographics, charts and similar elements on this page, may be found below. Homepage Quick links Quick links. GO Results hosted on duckduckgo. Main navigation Data Open related submenu Data. Latest data Prevalence of drug use Drug-induced deaths Infectious diseases Problem drug use Treatment demand Seizures of drugs Price, purity and potency. Drug use and prison Drug law offences Health and social responses Drug checking Hospital emergencies data Syringe residues data Wastewater analysis Data catalogue. 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Uppsala buying Ecstasy