How can I buy cocaine online in Ha Long

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How can I buy cocaine online in Ha Long

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. Most indicators continue to suggest that cocaine availability on European consumer markets remains at historically high levels and that the markets continue to expand across Europe. While most cocaine consumers remain concentrated in a limited number of western and southern European countries, whose markets appear to be continuing to expand, there are also indications that cocaine retail markets continue to grow in northern and eastern Europe. However, there are also indications that these markets are growing and are emerging in countries where they were not observed before. Affordability of drugs is a measure that incorporates drug purity and accounts for differing national economic conditions as quantified in the price level indices PLI for fuller details and limitations, see Groshkova et al. Affordability allows a more sophisticated comparison of retail drug markets across countries and over time. Source: The source data for this graphic is available in the source table on this page. This finding is in line with trends noted in other indicators of retail markets such as retail prices and purity, estimated prevalence of drug use, wastewater analysis and numbers of cocaine seizures, which all suggest a further increase in cocaine availability since the last edition of this report EMCDDA and Europol, It should also be noted that cocaine affordability in Europe does not appear to have been impacted by the COVID pandemic and associated measures restricting movement in Europe, as it remained stable or slightly increased in see Figure Changes in average affordability of cocaine in a group of 16 EU Member States. The purity of cocaine at the retail level has been increasing in Europe since , and in it reached its highest level in the last decade, although adulteration continues to take place see Box Recent trends in cocaine adulteration. Overall, the retail price of the drug remained stable between and This appears to confirm the trend, identified in the previous edition of this report, that more cocaine is now available on European retail markets than before EMCDDA and Europol, The COVID pandemic does not seem to have impacted retail prices or the increase in purity recorded since in significant ways, even if a slight increase in price and a stabilisation of purity can be observed in see Figure Indexed trends in cocaine retail price and purity. This is likely due to an increase in the availability of high-purity cocaine at the wholesale level see Box Profiling European cocaine and to competition between the numerous criminal networks involved at the various levels of the cocaine market see Cocaine: increasingly attractive for a wider range of criminal networks. The increasing production of cocaine hydrochloride in Europe may also have played a role see Section Manufacturing cocaine: new developments highlight larger European role in global production. In Europe, the retail market for cocaine has historically been concentrated in the western and southern parts of the continent. This is where most of the drug first enters the EU, and they are the most populated and wealthiest regions of Europe. Data on prevalence of cocaine use, expressed in estimated numbers of users during the last year, may be viewed as an indicator of the location and approximate size of retail markets, with the latest available data signalling that the largest retail markets continue to be located in western and southern Europe. Two Nordic countries, Denmark and Sweden, follow these countries, but report much lower estimated numbers of users. Meanwhile, the available data indicate that Poland may be the largest cocaine market in eastern Europe. However, due to a lack of recent general population survey data from some countries in this part of Europe, this may not be the case. While western and southern Europe remain the main markets, signs such as cocaine consumption becoming more common in cities in eastern Europe suggest that the cocaine retail market is also developing in other regions EMCDDA, Recent trends based on data from 15 countries that have conducted surveys on last year cocaine use since indicate that levels of use are increasing in 8 countries, remaining stable in 5 and decreasing in 2 EMCDDA, a. While an overall decrease in cocaine use was visible in , likely due to COVID and the restrictions imposed on social gatherings and the nightlife scene, there are indications of recovery in and overall signals that the cocaine retail market continues to expand. Wastewater information provides some details on the characteristics of European cocaine retail markets see Overview of data and methods. Likely due to a temporary reduction in cocaine use during the initial lockdown period of the COVID pandemic, data on cocaine residues namely the benzoylecgonine cocaine metabolite in municipal wastewater showed a decrease in the majority of cities in compared to EMCDDA, However, in an increase in cocaine residues was observed in 32 out of 58 cities compared to , with 12 reporting no change and 14 reporting a decrease EMCDDA, a. Furthermore, wastewater data from 12 European cities covering the period show increasing longer-term trends. While this cannot be readily interpreted as an increase in the number of cocaine users, although this is a possible explanation, other factors could have caused this increase in metabolites. Higher concentrations of metabolites could mean that the same number of people used more cocaine, or they could reflect the increased purity of cocaine found on European retail markets. A combination of these three causes could also be an explanation. Treatment data can also provide some insight into the drug retail trade. Between , first-time entries to specialised drug treatment for cocaine problems increased in 14 countries EDR Overall, new entries to treatment for problems associated with cocaine use have increased in Europe since Most of the drug seizures reported in Europe are of small amounts of under 10 grams, likely confiscated on retail markets. Out of the 26 countries with sufficient data, only Bulgaria and Greece, which report comparatively small numbers of cocaine seizures, did not report a decrease between and Indeed, as already mentioned, lockdowns across Europe impacted on levels of cocaine use, and it is also probable that less police time and resources were focused on enforcing drug laws at retail level in , since many officers were mobilised in the enforcement of COVID restrictions. However, the impact of COVID on European retail markets for cocaine in should not obscure the steady increase in the number of cocaine seizures observed between and , a general trend which, put in the context of the other indicators reviewed in this report, may have only been temporarily interrupted by the effects of COVID In this respect, it will be important to continue monitoring numbers of cocaine seizures in Europe in the future. The country reporting the largest estimated number of cocaine seizures in and in previous years is Spain 35 followed by Italy 7 , Belgium 5 , and Sweden 4 However, it must be noted that data are not available for several countries usually reporting large numbers of seizures. The countries reporting the highest numbers of seizures also report some of the highest estimated numbers of cocaine users. It should be noted that the Netherlands, one of the top retail markets in terms of numbers of cocaine users, does not report numbers of drug seizures and as a result is not included in this analysis. Trends in numbers of seizures and other indicators presented in the edition of the EU Drug Markets Report EMCDDA and Europol, suggested that the largest cocaine retail markets of western and southern Europe continued growing, while other markets were emerging or expanding in eastern Europe and in the Nordic countries. New seizure data broadly confirm that these trends continued until the shock caused by COVID in East European countries generally report much lower numbers than the rest of Europe, reaching a few hundred cocaine seizures annually at the most. Seven countries Estonia, Croatia, Latvia, Lithuania, Hungary, Romania and Slovakia reported record numbers of cocaine seizures in However, data from the police are not available, so this may not reflect the true level. Furthermore, Turkey reported 3 cocaine seizures in , seven times the number reported in and the seventh largest number of cocaine seizures in Europe that year. Although the number of Turkish seizures started declining after the peak of 3 , it remains at significantly higher levels than in the mids, continuing to suggest that a sizeable cocaine retail market exists in Turkey see Figure Indexed trends in numbers of cocaine seizures in 11 Eastern EU countries and Turkey. Similarly, Danish, Finnish and Norwegian seizures were more numerous in and than in Denmark and Finland, like Sweden, broke records in , before the pandemic hit Europe. Historically, small freebase cocaine markets have existed in a few western and southern European countries including Germany, Spain, France, Italy and the Netherlands. The available information indicates that use of freebase cocaine in eastern and northern Europe continues to be very limited. Although there is little doubt that the European market for smokeable freebase products is much smaller than the market for hydrochloride powders, it is difficult to monitor and the data available at present are unlikely to reflect its true dimension. Should the other main freebase cocaine markets in Europe have experienced a similar increase in the number of users over this time period, of which there are some indications, then there would potentially be over freebase cocaine users in Europe. An important distinction between the two cocaine markets is that while cocaine powders are invariably bought from dealers, the freebase market involves products that are either manufactured by the users themselves from purchased powders or purchased as crack from dealers. Based on the available evidence, it is difficult to estimate which of these two types of products is the most prominent, but basification for own use i. Those who manufacture their own freebase products may not identify themselves as crack users but as cocaine users, which may lead to an underestimation of the number of freebase cocaine users in Europe EMCDDA and Europol, Thus, for a number of reasons, it is likely that the European market for freebase cocaine products is both underestimated and under-documented. Caution is therefore required when interpreting the available data. Freebase cocaine is primarily smoked, but some users inject it. In some countries such as France and Portugal, low-threshold facilities report that injection of freebase is not infrequent. Freebase users appear to predominantly belong to vulnerable high-risk populations, and are often also current or former users of opioids. Migrants from Africa and east European countries are reported to make up a sizeable proportion of freebase cocaine users in some EU Member States. There are also indications of cocaine freebase use among some recreational drug users in France and Italy, which suggest that use is spreading to a new customer base. Only a handful of countries report the number of crack cocaine seizures consistently, and as a result it is difficult to distinguish trends. Nevertheless, it would appear that since the last edition of this report EMCDDA and Europol, , seizures have continued to be relatively stable and low in both numbers and quantities among the reporting countries. However, other datasets suggest that in recent years, some long-standing freebase markets may have grown, although they remain small, while new markets seem to have emerged in countries where they previously were not observed, resulting in an increase in Europe as a whole. For example, the overall number of people seeking treatment for problems with crack use tripled between and , when 7 people entered treatment. Notable increases were observed in countries with long-standing markets, such as Spain, France and Italy, but also in others including Belgium, Ireland and Portugal. Crack use was also reported in some German cities where it was rarely observed in the past. Similar trends emerge from other datasets. For instance, low-threshold services in Brussels, Lisbon and some areas of Ireland and Italy reported a significant increase in the number of crack users among their clients in In addition, wastewater analysis performed in 13 cities of six western European countries in found freebase residues in all cities and during all sampling days, indicating daily use EMCDDA, b. The highest loads were encountered in Amsterdam and Antwerp, that is, in cities located in countries identified as major entry points for wholesale cocaine shipments to the EU see Section Exploitation of global logistics: European and Latin American ports. Cocaine freebase markets often entail serious consequences in terms of public health and security, and can be particularly challenging to deal with for the public services concerned. Dependence on crack cocaine is characterised by high-frequency use, serious mental and physical health problems, and aggression. Notable harms associated with cocaine freebase use in Europe include intimidation, violence and forced prostitution, and it frequently leads individuals to financial ruin. At the global level, and particularly in South America, a bigger range of smokeable cocaine products are available to consumers than in Europe. The majority are made from the intermediary products, coca paste and cocaine base, that are formed during the manufacture of cocaine hydrochloride from coca leaves see Figure The cocaine production process and the different cocaine products. These are smuggled in wholesale amounts within and across borders from production areas in Bolivia, Colombia and Peru. In some South American countries, especially the three main cocaine-producing countries, there is evidence to suggest that markets for smokeable products are larger than those for powder cocaine UNODC, e. As already mentioned, the availability in Europe of large quantities of coca paste and cocaine base creates a risk that new smokeable cocaine consumer products similar to those available in South America could emerge on the European market in the future see Section Manufacturing cocaine: new developments highlight larger European role in global production. Compared to other aspects of the cocaine market, there is limited systematic information available on the methods used to retail cocaine directly to consumers in Europe. Overall, the nature of the connections between the players active at different levels of the market — importation, wholesale distribution, mid-market distribution and retail sales — is generally poorly documented. Until more and better data are systematically collected on these aspects, it will be difficult to paint a comprehensive picture of how the cocaine retail market operates in Europe. That said, like the diversification of the criminal networks involved in the importation and distribution of cocaine in Europe analysed earlier see Cocaine: increasingly attractive for a wider range of criminal networks , some evidence exists to show that retail markets have seen the emergence of new players and are becoming more diverse, in terms of where and how they operate. While research on the cocaine retail trade is limited, it is generally thought that face-to-face methods for buying and delivering cocaine to consumers is most common. However, data collected through novel methods and on internet-based platforms have provided some insights into the market and how it may be changing. The diversification of the cocaine retail market has potentially been influenced by, among other things, the direct delivery to consumers of small amounts of cocaine purchased through the darknet. There is relatively good data on darknet markets, which have provided insights into estimated sales volumes, for example. Based on such data, cocaine has been estimated to be one of the drugs that generates the highest revenues for dealers operating in anonymised darknet markets. While darknet markets have been a relatively important source of supply for European cocaine consumers, there are indications that they are losing ground as a method for retailing cocaine and other drugs Groshkova et al. Research and analysis also suggest that public social media platforms and encrypted communication tools are commonly and potentially increasingly used across Europe for mid-level and retail cocaine trafficking. In Sweden, for example, ongoing research has found that the retail drugs trade has moved increasingly to social media platforms Bloem and Svederborn, , with one study finding that cocaine is offered in smaller quantities on Facebook compared to one of the largest Swedish cryptomarkets, namely Flugsvamp 2. Web-based surveys can also be a quick and inexpensive tool for collecting information from relatively large numbers of people who use drugs. While their results cannot be generalised to the population as a whole, or indeed to all people who use drugs, they can paint a detailed and timely picture of drug consumption and purchasing patterns and are a useful complement to traditional data-collection methods. A smaller proportion of these respondents provided detailed information enabling further analysis of how cocaine is retailed in Europe. Interestingly, the use of these methods differed between countries. While this indicates that some methods of purchase are more common in some countries than others, indicating that the retail markets may differ somewhat across Europe, it should be stressed that sample sizes were very small in several countries. Source: European Web Survey on Drugs, Twenty-one EU countries and Switzerland. The source data for this graphic is available in the source table on this page. The Figure In the last 12 months, how was the cocaine powder usually delivered to you? Similarly, the use of delivery methods greatly differs between countries, again suggesting differences among European countries. Early analysis on the impact of the pandemic on EU drug markets indicated that the effects of COVID restrictions appeared to be more noticeable at the retail level than at the wholesale level. Although large quantities of cocaine were available in Europe, the logistics of transporting smaller batches, including retail quantities, were more difficult to orchestrate. New modi operandi observed in some EU Member States indicated that some dealers quickly adapted to new challenges. It is too early to tell whether the pandemic will have any lasting effects on the retail trade for cocaine in Europe. It will be important to continue monitoring these aspects in the coming years. Although caution is needed in interpreting these data, the number of listings provides a useful indicator of the scale of activity on darknet markets. Compared with data from previous monitoring periods, when the origin of cocaine offered on darknet markets was limited to a few EU Member States EMCDDA and Europol, , the current data show considerable diversification, with cocaine now apparently being shipped from every corner of the EU. The typical quantity most frequently observed value of cocaine powder offered was 10 grams 1 listings , followed by 20 grams 1 The typical price per gram was consistently EUR 60 per gram, up to 50 grams, at which point a bulk discount was evident — listings of 50 grams and grams were typically offered at EUR 50 per gram. The typical quantity of crack offered was 1 gram 14 listings , followed by 0. There were listings of 1 kilogram or more cocaine powder. There were 47 listings for 2 kilograms; one listing each for 2. However, price data were not available for these quantities. The Netherlands and Germany together accounted for over half of the listings of bulk quantities see Figure Proportion of bulk cocaine listings on major darknet markets shipping from EU countries. Consult the list of references used in this resource. Homepage Quick links Quick links. GO Results hosted on duckduckgo. Main navigation Data Open related submenu Data. 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Breadcrumb Home Publications European Drug Markets Cocaine Cocaine retail markets: multiple indicators suggest continued growth and diversification. On this page. Cocaine retail markets: multiple indicators suggest continued growth and diversification. PDF is being prepared. This make take up to a minute. Once the PDF is ready it will appear in this tab. Sorry, the download of the PDF failed. Last update: 6 May

Single Low Dose of Cocaine–Structural Brain Injury Without Metabolic and Behavioral Changes

How can I buy cocaine online in Ha Long

Official websites use. Share sensitive information only on official, secure websites. Priolli depriolli terra. This article was submitted to Neuropharmacology, a section of the journal Frontiers in Neuroscience. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Chronic cocaine use has been shown to lead to neurotoxicity in rodents and humans, being associated with high morbidity and mortality rates. However, recreational use, which may lead to addictive behavior, is often neglected. This occurs, in part, due to the belief that exposure to low doses of cocaine comes with no brain damage risk. Cocaine addicts have shown glucose metabolism changes related to dopamine brain activity and reduced volume of striatal gray matter. This work aims to evaluate the morphological brain changes underlying metabolic and locomotor behavioral outcome, in response to a single low dose of cocaine in a pre-clinical study. In this context, a Balb-c mouse model has been chosen, and animals were injected with a single dose of cocaine 0. Control animals were injected with saline. A behavioral test, positron emission tomography PET imaging, and anatomopathological studies were conducted with this low dose of cocaine, to study functional, metabolic, and morphological brain changes, respectively. Animals exposed to this cocaine dose showed similar open field activity and brain metabolic activity as compared with controls. However, histological analysis showed alterations in the prefrontal cortex and hippocampus of mice exposed to cocaine. For the first time, it has been demonstrated that a single low dose of cocaine, which can cause no locomotor behavioral and brain metabolic changes, can induce structural damage. These brain changes must always be considered regardless of the dosage used. It is essential to alert the population even against the consumption of low doses of cocaine. Keywords: cocaine, brain damage, metabolic imaging, histological change, behavior. Drug dependency is considered a physical and psychological condition that induces chronic and recurrent diseases. The continued use of psychoactive substances can cause functional changes in the brain Dias et al. Cocaine is one of the most widely used drugs in the world. The European Drug Report of showed that about 4. In , the number of young people who have already had any contact with illicit drugs was , European Drug Report, Its consumption reaches about 0. It is well-established that cocaine is a psychostimulant Kalivas, This drug inhibits the reuptake of monoamine neurotransmitters, including dopamine DA and noradrenaline NA. The DA increase occurs in the mesocorticolimbic system the brain reward system , which is responsible for the well-being sensation and euphoria, thus playing a major role in the addiction process Planeta et al. DA auto-oxidation can lead to oxidative stress and apoptosis Dias et al. There is evidence that oxidative stress contributes to cocaine neurotoxicity Dietrich et al. Changes in brain circulation triggered by cocaine use led to additional brain injury risk Niu et al. Browndyke et al. Moreover, cerebrovascular accidents rank amongst the most severe adverse events from cocaine abuse Sordo et al. Pre-clinical neuroimaging studies aiming to model human diseases and traits have been increasing in the last decade Volkow et al. In an animal model, individuals can be followed up longitudinally over time, allowing the study of disease progression, development of compensatory changes, and long-term evaluation of the safety and efficacy of interventions Zaidi, ; Cannella et al. In particular, pre-clinical positron emission tomography PET plays a fundamental role, not only in the validation of animal models of human brain disease but also in the quantitative measurement of regional changes in brain activity. These regional alterations in cerebral sub-regions are affected by diseases or psychoactive agents such as drugs of abuse. There is also evidence that repeated administration of a psychostimulant drug in laboratory animals may cause a change of different parameters, including cerebral glucose metabolism, in opposition to the one caused by an acute administration Hammer and Cooke, ; Zocchi et al. The selectivity of glucose metabolism changes in the basal ganglia and prefrontal cortex PFC suggests that regional metabolic changes, observed in cocaine users during detoxification, are related to changes in the DA activity in the brain Volkow et al. Several studies used brain imaging techniques to investigate the changes in brain activity induced by drugs Hammer et al. Particularly, PET studies using 2-deoxy\[ 18 F\]fluoro- d -glucose 18 F-FDG have demonstrated abnormal brain glucose metabolism connected to cocaine addiction and withdrawal. The 18 F-FDG is a widely used radiotracer in PET due to its convenient half-life min and its well-established role in glycolytic metabolism Alavi and Reivich, ; Caprioli et al. Regarding pre-clinical models, some authors evaluated the metabolic activity changes after short 1 week and long 4 weeks periods of cocaine abstinence in rats with a history of cocaine self-administration, using the escalation model Nicolas et al. They showed that escalation of cocaine self-administration produced cerebral changes that are quantitatively and qualitatively different from those found after short access to cocaine self-administration; i. Although there are a growing number of neuroimaging studies in cocaine addiction settings, there are no neuroimaging studies in the context of a single low dose of cocaine. Additionally, data on the potential for brain injury induced by the consumption of low doses of cocaine remain scarce Volkow et al. The present work puts forward the hypothesis that even a single low dose of cocaine can cause deleterious brain changes. Therefore, this work aims to evaluate locomotor behavioral, metabolic, and morphological brain data of mice exposed to a single low dose of cocaine. Male Balb-c mice, with a mean age of 6 weeks and an average weight between 20 and 30 g, were used in this study. Our general experimental design is presented in Figure 1. The non-exposed animals represent the controls that were injected intraperitoneally i. The exposed group was injected also i. The dose was chosen based on the lowest dose having demonstrated dopaminergic visible action on PET imaging evaluation in human volunteers Heard et al. General experimental design. Mice were submitted to a behavioral study. Five animals from each group were subsequently studied by PET imaging analysis. To histological analysis, six randomized mice brain samples were collected. Animals were submitted to a behavioral test followed by PET imaging; and brains were collected. Initially, saline or cocaine was administered to the animals, which subsequently underwent a behavioral test for 60 min. Afterwards, five randomized mice from each group were injected i. The radiotracer had an uptake period of 50 min post-injection. Subsequently, animals were anesthetized i. The open field maze OFM test has been used to assess general motor activity and anxiety Gould et al. The animals were allowed a habituation period of 45 min to the behavioral test room before the OFM test procedure. A soundproof test room was used. Moreover, the behavioral test was performed under a white noise 80 dB stimulus to further attenuate sound interference Henry et al. Additionally, the light level inside the OFM was maintained at 7—8 lux. Following saline or cocaine administration, animals were immediately placed in the middle \[AS4\] of the open field, and motor activity was monitored through a video camera positioned above the apparatus. The animals were allowed to move freely in the OFM for 60 min. The OFM evaluation was performed by analyzing the following parameters: a total walked distance; b mean speed; c maximum speed; d periphery distance; e time spent in the periphery; f latency time to center; g the number of entrances in the center; h center distance; and i time spent in the center. A metabolic PET scan with 18 F-FDG was performed, under basal conditions in fasted animals 6—8 h , to study the cerebral metabolic rate of glucose consumption. This innovative scanning method, in which the detector modules are always face to face, strongly reduces parallax errors, thus simultaneously achieving a great level of detail and spatial resolution. Detector arrays can have different geometries. The easy PET. According to the experimental design Figure 1 , awake mice were i. For optimal radiotracer distribution, mice were kept conscious during the uptake period 60 min. Fifty minutes post-radiotracer injection, the animals were anesthetized i. The anesthetized animals were placed on the bed of the easy PET. The PET imaging acquisition started, taking place during 30 min. Since cerebral metabolic rates of glucose consumption are reflected by local radiotracer uptake, a qualitative analysis of changes in brain metabolic activity of animals non-exposed or exposed to a single low dose of cocaine was done. In order to improve the image visualization, the hot metal scale was selected, and a threshold was applied. Semi-quantitative measurements of glucose metabolism were obtained using the standardized uptake value SUV , which is a normalized target-to-background measure. Usually, a density equivalent to 1. Areas too small to be identified using a microPET system were not included in this analysis. Macroscopy and microscopy analyses were done for the whole brain and different brain areas. The number of neuronal cells was obtained as an average of three randomly selected fields of three sections from each animal. The statistical Package Bioestat version 5. Exploratory and locomotor activities of mice injected with a low dose of cocaine in an open field apparatus were evaluated. The OFM analysis showed no differences in the behavior of neither group of mice non-exposed or exposed to cocaine. Open field behavior study. Figure 3 illustrates the metabolic activity in mice non-exposed saline injection compared with mice exposed to cocaine. According to the intensity of the colormap selected hot metal , the presence or absence of abnormal radiotracer accumulation was analyzed. The size and intensity of the uptake region, especially when the accumulation was focal, was also associated. Additionally, PET analysis of the entire brain showed no statistically significant alterations between groups Figure 4. PET imaging study. Changes in metabolic activity in animals non-exposed controls and exposed to a single dose of cocaine 0. The atlas-derived volumes of interest VOIs of the main areas commonly affected by cocaine are shown superimposed on transverse, coronal, and sagittal image slices of mice brain from both representative 18 F-FDG PET studies and CT derived from Digimouse 3D atlas. Bar graph of the statistical analysis of standardized uptake value SUV in animals non-exposed and exposed to a single low dose of cocaine. B Metabolic all-brain analysis. Note the absence of metabolic changes. No histological differences between groups were found for the Cb. On the contrary, morphological lesions were found in the PFC of mice exposed to cocaine, ranging from mild gliosis up to ischemic tissue necrosis. Additionally, histological analysis showed morphological deterioration and low neural count in PFC and HC in all animals exposed to cocaine. It is also noteworthy that the HC granular layer of the group exposed to a single low dose of cocaine was clearly distinct from that of controls. ML, molecular layer; G, granular layers; WM, white matter. Cocaine did not trigger any histopathological changes. Animals exposed to cocaine show hippocampal histopathological changes in the pyramidal cell layer and granule cell layer in the CA1 region and dentate gyrus , respectively, with neuronal loss G,H. Animals depthwise to cocaine present histological changes, including ischemic necrosis P,Q. Observe arrow the clear halo around oligodendrocyte nuclei O,R. These features demonstrate irreversible hypoxic lesions and the presence of granule-adipose cells O,P. Acute exposure to cocaine in humans includes euphoria, high self-confidence, motor arousal, restlessness, increased sensory perceptions, mood changes, irritability, impulsivity, anxiety, fear, paranoia, and avoidance Silva et al. These symptoms are dependent upon the extension of cocaine impact to affected brain areas Gallucci Neto et al. Although there is a robust body of literature regarding acute high doses of cocaine, as well as cocaine addiction scenarios, an integrated analysis of behavioral, metabolic, and structural brain changes associated with an acute low dose of cocaine is lacking. Herein, the locomotor and exploratory behaviors associated with a low dose of cocaine using an OFM test were firstly analyzed. The presented behavioral data suggest that this cocaine dose 0. In the present study, 0. Thus, the absence of locomotor behavioral changes seen herein was expected. There is less information regarding the behavioral effects of cocaine in Balb-c mice, which is the strain used herein. However, the emotional and cognitive behaviors associated with cocaine for this mouse strain remain to be characterized. This should be done in future investigations. The 18 F-FDG PET imaging study performed herein showed no significant differences between controls and mice exposed to a single low dose of cocaine. This could be explained by the very low cocaine dose used. The experimental design could also be responsible for the absence of alteration in the PET analysis. It is noteworthy that it has been demonstrated that after i. Therefore, the lack of metabolic changes that are seen here may reflect cocaine pharmacokinetics. In fact, this PET analysis may have been performed at a time point where there were only vestigial plasmatic cocaine levels. There are only a few studies looking at acute pharmacological effects of cocaine on rodent brain glucose metabolism. An acute intravenous administration of cocaine 0. Nonetheless, the distribution pattern of these changes is different between the two strains. Briefly, in the referred study, rodents were sequentially intravenously injected with cocaine and with 2-\[ 14 C\]deoxyglucose. Animals were sacrificed 40 min after the administration of the tracer, and brains were collected for glucose consumption assessment. These results are aligned with the findings in primates, also obtained using the quantitative 2-\[ 14 C\]deoxyglucose method Lyons et al. These authors co-injected cocaine and \[ 18 F\]-FDG and performed a static PET scan starting 40 min post-injection image acquisition during 30 min. These apparently discrepant results may, however, highlight that cocaine acutely recruits cortical and subcortical regions and changes their metabolism in different species. Nonetheless, other studies are needed to see whether these metabolic alterations are long-lasting e. Additionally, cocaine-induced activation was shown to be far less robust following withdrawal in a cocaine self-administration setting Henry et al. This suggests that a history of cocaine use may impact the acute metabolic effects of cocaine. Finally, this absence of metabolic changes seems consistent with the lack of locomotor behavioral changes. In this context, the authors are already planning to perform PET scan analysis immediately after cocaine i. Notably, cocaine induced histological alterations in PFC and HC, which are suggestive of mild gliosis up to ischemic tissue necrosis Figure 5. Both PFC and HC have a crucial role in drug addiction processes, throughout the regulation of limbic reward regions and their involvement in higher-order executive and cognitive functions e. The histological changes seen in this study raise concerns regarding episodic consumption of low doses of cocaine. A growing body of evidence suggests that cocaine indirectly influences glutamate transmission Schmidt and Pierce, Therefore, one cannot rule out the role of glutamate in the cocaine-induced histological alterations reported here. Regarding the hippocampus , CA1 region is structured depthwise in defined layers: oriens, pyramidale, radiatum , and lacunosum-moleculare. The cell bodies of horizontal trilaminar cells and inhibitory basket cells are located in the oriens. Pyramidale layer contains the cell bodies of the pyramidal neurons, which are the main excitatory neurons of the hippocampus. This layer also contains the cell bodies of many interneurons, including axo-axonic cells, bistratified cells, and radial trilaminar cells. Radiatum layer contains commissural and septal fibers and Schaffer collateral fibers, which are projected to CA1. Laconosum is a thin layer and is often grouped with molecular stratum into a single layer named lacunosum-moleculare layer. Moreover, it contains Schaffer collateral fibers and perforant path fibers coming from the superficial layers of the entorhinal cortex. Dentate gyrus is part of the HC trisynaptic circuit and is thought to contribute to the formation of new episodic memories. This region promotes spontaneous exploration of novel environments, synaptic plasticity, rapid acquisition of spatial memory, and other functions Saab et al. The CA1 and DG are the most sensitive regions to hypoxia, and their examination is mandatory to investigate possible acute neuronal necrosis and gliosis Liu et al. In fact, glial alterations were visible in the present study. The nuclei of glial cells are also recognizable in HE: the nuclei of astrocytes and oligodendrocytes are round, with the first being larger and more loose. The nuclei of the microglia are elongated, comma-shaped, and dense. When there is damage to the nervous tissue, the microglial cells lose their extensions and assume a rounded shape, constituting macrophages with phagocytic capacity. Histological analysis suggests that microglia in the cocaine group have fine foamy cytoplasm since they phagocytize lipids derived from degenerated nervous tissue. In exposed cocaine mice, histology showed gemistocytic astrocytes, characterized by abundant and pink cytoplasm and eccentric nuclei. A clear halo around oligodendrocyte nuclei can also be observed Figure 5 , suggesting the entry of water into the cells due to hypoxia. Although there are few experimental studies about the Cb relationship to addictive drug behavior, evidence suggests that cerebellar activation may be involved in functions such as cognition, prediction, learning, and memory, being associated with compulsive and perseverative behaviors Carbo-Gas et al. The alterations in Cb resulting from chronic cocaine use have been correlated with its relationship and the maintenance of drug memory. Cb neurons and glia are arranged in layers. The molecular layer is located at the surface and contains the dendrites of Purkinje neurons, axons of granule cells parallel fibers , fibers of Bergmann glia, basket cells, and stellate cells. The granular cell layer contains granule cells, Golgi cells, Lugaro cells, and unipolar brush cells Hashimoto and Hibi, In general, Cb has a characteristic dopaminergic distribution. Dopaminergic fibers, projecting from the ventral tegmental area to the cerebellar cortex, terminate mainly in the granular layer and additionally in the Purkinje cell layer, but not at all in the molecular layer Ikai et al. This morphological characteristic can explain the absence of evident histological changes in animals exposed to cocaine. One should stress that the histological alterations did not translate into locomotor and metabolic changes. This suggests that structural changes should be more profound and more widely spread across the brain to trigger functional brain changes. Nevertheless, the animal model presents some limitations, such as the inability to evaluate sociocultural and genetic factors, and personality and psychological traits, which are relevant issues to determine drug addiction development in humans El Rawas et al. Future studies need to assess if these structural changes persist e. Overall, it is shown, for the first time, that a single low dose of cocaine, which did not change locomotor behavior and brain metabolism, has the potential to induce structural neurological damage. There is no safe dose for cocaine exposure. Brain structural changes must be considered regardless of the used dosage. It is essential to alert the population against any consumption, not underestimating acute and recreational dosage since the use, even in a low single dose, can generate structural tissue damage. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. CN and DP: conception of the presented idea. JR: experiment execution OFM. ML: experiment execution histological analysis. FP and MB: helped supervise the project. All authors discussed the results and contributed to the final manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Front Neurosci. Find articles by Camilla Nicolucci. Find articles by Mariana Lapo Pais. Find articles by A C Santos. Find articles by Fabiana M Ribeiro. Find articles by Ana L M Silva. Find articles by I F Castro. Find articles by Pedro M M Correia. Find articles by Julie Reis. Find articles by Marina Z Lopes. Find articles by Maria F Botelho. Find articles by Frederico C Pereira. Find articles by Denise G Priolli. Received Jul 31; Accepted Dec 15; Collection date 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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