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You are bound by Japanese local laws and subject to the penalties accordingly while in Japan. Be aware that some of the local laws and penalties may seem to be harsher than the standards of your country. All students are urged to observe Japanese drug laws, which are rigorously and strictly enforced. The possession, receipt, use and sale of drugs, including marijuana, is subject to investigation by the Japanese customs and police authorities. Any student convicted of these crimes will be expelled from our program immediately. Persons arrested in Japan, even for a minor offence, may be held in detention without bail for two to three months during the investigation and legal proceedings. Further, penalties for drug offences include lengthy imprisonment. Use or possession of small amounts of drugs may result in a prison sentence of between one and ten years and Japanese law allows for a fine of up to 5,, yen. Some people convicted of drug related offences have been issued a deportation order. People deported under these circumstances are not permitted to return to Japan for five to ten years. You should also be aware that Japanese authorities aggressively pursue drug smugglers with sophisticated detection equipment, drug-detecting dog, and other methods. The Japanese police make arrests for even the smallest amounts of illegal drugs. Bringing Medicine into Japan. Drug Laws in Japan.

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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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