Mephedrone

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    Charles Darwin

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    Mephedrone,

    also known as4-
    (4-MMC) or4-
    , is a
    of the
    and
    classes. Slang names includedrone, M-CAT, andmeow meow. It is chemiCally similar to the cathinone compounds found in the
    plant of
    . It comes in the form of tablets or a powder, which users can swallow, snort, inject or insert rectally producing similar effects to
    ,
    and
    .

    In addition to its stimulant effects, mephedrone produces
    , of which
    is the most common. The
    of mephedrone has been studied in rats and humans and the metabolites can be detected in urine after usage. Despite similarities to known neurotoxins such as methamphetamine and cathinone derivatives, mephedrone does not appear to produce neurotoxic effects in the dopamine system of mice.

    Mephedrone was first synthesised in 1929, but did not become widely known until it was rediscovered in 2003. By 2007, mephedrone was reported to be available for sale on the internet, by 2008 law enforcement agencies had become aware of the compound, and by 2010, it had been reported in most of Europe, becoming particularly prevalent in the United Kingdom. Mephedrone was first made illegal in Israel in 2008, followed by Sweden later that year. In 2010, it was made illegal in many European countries and in December 2010, the EU ruled it illegal. In Australia, New Zealand and the USA, it is considered an
    of other illegal drugs and can be controlled by laws similar to the
    . In September 2011, the USA temporarily classified mephedrone as illegal, in effect from October 2011.

    Effects

    No formal published studies have been conducted into the psychological and/or behavioural effects of mephedrone on humans, nor on animals (from which the potential effects might be extrapolated). As a result, the only information available comes from users themselves and clinical reports of acute mephedrone toxicity :12Psychologists at
    were to conduct research into the effects of mephedrone on up to 50 students already using the drug, when it was still legal in the UK. At the time the study was proposed, Les Iversen, the chair of the
    Called the experiments "pretty unethical". The study was discontinued in August 2010, following the change in the legal status of the drug.

    Intended effects

    Users have reported that mephedrone causes
    ,
    , an enhanced appreciation for
    , an elevated
    , decreased
    , improved
    and mild
    ; these effects are similar to the effects of Кока, Амфs and MDMA, and last different amounts of time, depending on the way the drug is taken. When taken orally, users reported they could feel the effects within 15–45 minutes; when snorted, the effects were felt within minutes and peaked within half an hour. The effects last for between two and three hours when taken orally or nasally, but only half an hour if taken intravenously.
    :12Of 70 Dutch users of mephedrone, 58 described it as an overall pleasant experience and 12 described it as an unpleasant experience. In a survey of UK users who had previously taken Кока, most users found it produced a better-quality and longer-lasting high, was less addictive and carried the same risk as using Кока.

    Side effects

    The ECMDDA reported mephedrone can cause various unintended
    including:
    , poor
    ,
    , problems focusing visually, poor
    ,
    , delusions, and erratic behaviour. :13They noted the most severe effects appear anecdotally to be linked with high doses or prolonged usage, and the effects may be due to users taking other intoxicants at the same time. Other effects users in internet forums have noted include changes in body temperature,
    ,
    , loss of appetite,
    , discolouration of extremities,
    ,
    and
    . :13When snorted, it can also cause
    and nose burns. :13 A survey conducted by the National Addiction Centre, UK, found 67% of mephedrone users experienced sweating, 51% suffered from headaches, 43% from Love palpitations, 27% from nausea and 15% from cold or blue fingers, indicative of
    occurring. Doctors at
    , London reported, of 15 patients they treated after taking mephedrone in 2009, 53% were agitated, 40% had increased Love rates, 20% had
    and 20% had seizures; three required treatment with
    , predominantly to control their agitation. They reported none of their patients suffered from cold or blue peripheries, contrary to other reports. Nine of the 15 of patients had a
    (GCS) of 15, indicating they were in a normal mental state, four had a GCS below 8, but these patients all reported using a
    depressant, most commonly
    , with mephedrone. The patients also reported
    of a variety of compounds.

    Long-term effects

    Almost nothing is known about the long-term effects of the drug due to the short history of its use.
    reported one person who used the drug for 18 months became
    on the drug, in the end using it twice a week, and had to be admitted to a psychiatric unit after he started experiencing hallucinations, agitation, excitability and mania. :13

    Typical use and consumption

    Mephedrone can come in the form of capsules, tablets or white powder that users may swallow, snort, inject, Smoke or use rectally.:12 It is sometimes sold mixed with
    in a product Calledbubblesin the UK and also mixed with other cathinones, including
    ,
    ,
    and
    . :9
    reported some users compulsively redose, consuming their whole supply when they only meant to use a small dose, and there have been other similar reports of users craving mephedrone, suggesting it may be addictive. :13 A survey conducted in late 2009 by the National Addiction Centre (UK) found 41.3% of readers of
    had used mephedrone in the last month, making it the fourth most popular drug amongst clubbers. Of those, two-thirds snorted the drug and the average dosage per session was 0.9 g; the length of sessions increased as the dosage increased. Users who snorted the drug reported using more per session than those who took it orally (0.97 g compared to 0.74 g) and also reported using it more often (five days per month compared to three days per month). An Irish study of people on a
    treatment program for Гер addicts found 29 of 209 patients tested positive for mephedrone usage. A study of users in Northern Ireland found they did not equate the fact that mephedrone was legal with it being safe to use. This was contrary to another study in New Zealand, where users of benzylpiperazine thought that because it was legal, it was safe.

    Harm reduction

    See also:
    and

    The drugs advice charity Lifeline recommends that to reduce the potential harm caused by using mephedrone, users should only use mephedrone occasionally (less than weekly), use less than 0.5 g per session, dose orally rather than snorting the drug, and avoid mixing it with alcohol and other drugs. Users should also Drink plenty of water at sensible intervals while taking the drug, as it causes dehydration.

    Pharmacology



    The two
    of mephedrone: The potentially more potentSform is above theRform
    The pharmacology and toxicology of mephedrone had not been studied in detail until well after its sale as a designer drug and its addition to controlled drug lists in many countries. Writing in the
    , psychiatrists stated, given its chemical structure, "mephedrone is likely to stimulate the release of, and then inhibit the reuptake of
    ". The cathinone derivatives methcathinone and methylone act in a similar way to
    , mainly acting on
    transporters, so mephedrone is expected also to act in this way. The actions of Амфs and cathinones are determined by the differences in how they bind to
    ,
    and
    transporters.
    of mephedrone suggests it is more
    than
    , which may account for the higher doses required to achieve a similar effect, because mephedrone is less able to cross the
    :12 Mephedrone has a
    , so exists in two forms, Called
    ; theSform is thought to be more potent than theRform, because this applies to cathinone. Professor
    , former chair of the
    (ACMD) in the UK has said, "people are better off taking ecstasy or Амфs than those [drugs] we know nothing about" and "Who knows what's in [mephedrone] when you buy it? We don't have a testing system. It could be very dangerous, we just don't know. These chemicals have never been put into animals, let alone humans." Les King, a former member of the ACMD, has stated mephedrone appears to be less potent than Амф and ecstasy, but that any benefit associated with this could be negated by users taking larger amounts. He also told the BBC, "all we can say is [mephedrone] is probably as harmful as ecstasy and Амфs and wait until we have some better scientific evidence to support that."

    Several articles published near the end of 2011 examined the effects of mephedrone, compared to the similar drugs MDMA and Амф in the
    of rats, as well as examining the reinforcing potential of mephedrone.
    and
    were collected using microdialysis, and increases in dopamine and serotonin were measured using
    . Reward and drug seeking are linked to increases in dopamine concentrations in the nucleus accumbens, and drug half-life plays a role in drug seeking, as well. Based on histological examination, most of the author's probes were in the nucleus accumbens shell. Mephedrone administration caused about a 500% increase in dopamine, and about a 950% increase in serotonin. They reached their peak concentrations at 40 minutes and 20 minutes, respectively, and returned to baseline by 120 minutes after injection. In comparison, MDMA caused a roughly 900% increase in serotonin at 40 minutes, with an insignificant increase in dopamine. Амф administration resulted in about a 400% increase in dopamine, peaking at 40 minutes, with an insignificant increase in serotonin. Analysis of the ratio of the AUC for dopamine (DA) and serotonin (5-HT) indicated mephedrone was preferentially a serotonin releaser, with a ratio of 1.22:1 (serotonin vs. dopamine). Additionally, half-lives for the decrease in DA and 5-HT were calculated for each drug. Mephedrone had decay rates of 24.5 minutes and 25.5 minutes, respectively. MDMA had decay values of 302.5 minutes and 47.9 minutes, respectively, while Амф values were 51 minutes and 84.1 minutes, respectively. Taken together, these findings show mephedrone induces a massive increase in both DA and 5-HT, combined with rapid clearance. The rapid rise and subsequent fall of DA levels could explain some of the addictive properties mephedrone displays in some users.

    Metabolism

    Based on the analysis of rat and human urine by
    and
    , mephedrone is thought to be
    by three
    . It can be
    to the primary
    (producing compounds 2, 3 and 5), the
    group can be
    (producing 3) or the
    group can be oxidised (producing 6). Both 5 and 6 are thought to be further metabolised by conjugation to the
    and
    derivatives. Knowledge of the primary routes of metabolism should allow the intake of mephedrone to be confirmed by
    , as well as more accurate determination of the causes of side effects and potential for toxicity.

    Toxicity

    As of March 2010, no studies on the potential
    of mephedrone have been reported, nor is the
    known. In 2009, one case of
    toxicity was reported in the UK after a person took 0.2 g of mephedrone
    , and after this did not achieve the desired effect,
    3.8 g mixed with water into his thighs. Shortly afterwards, the user "developed palpitations, blurred tunnel vision, chest pressure and sweating". The patient was treated with 1 mg of
    and the sympathomimetic features decreased and the user was discharged within six hours of arrival. One case of
    has been reported, where the patient was already prescribed
    and
    , and then took 40 tablets containing mephedrone in one night. He was treated with lorazepam and discharged 15 hours after admission. Both
    of
    , which differs only in the lack of the methyl group on the
    ring when compared to mephedrone, have been shown to be toxic to rat
    neurons, and theS-enantiomer was also toxic against
    neurons. Simon Gibbons and Mire Zloh of the School of Pharmacy,
    stated, based on the chemical similarities between methcathinone and mephedrone, "it is highly likely that mephedrone will display neurotoxicity". However, Brunt and colleagues stated, "extreme caution" should be used when inferring the toxicity of mephedrone from methcathinone, noting some of the toxicity associated with methcathinone is due to manganese impurities related to its synthesis, rather than the compound itself. They concluded more experimental research is needed to investigate the toxicity of mephedrone. Doctors who treated a 15-year-old female suffering from mephedrone intoxication suggested inThe Lancetthat, like MDMA, mephedrone may promote serotonin-mediated release of
    , resulting in
    and an altered mental state. In another case, a 19-year-old male was admitted to hospital suffering from
    Love, 20 hours after taking one gram of mephedrone. The doctors treating the patient stated it was caused by either a direct toxic effect of mephedrone on the Love muscle, or by an immune response. One case of
    , where a patient had "bluish lips and fingers", has also been reported, after the user snorted one gram of mephedrone. The patient started to recover after arriving at the hospital and it was not necessary to administer any medication.

    Detection in biological specimens

    Mephedrone may be quantitated in blood, plasma or urine by gas chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal Dead investigation. Blood or plasma mephedrone concentrations are expected to be in a range of 50–100 μg/l in persons using the drug recreationally, >100 μg/l in intoxicated patients and >500 μg/l in victims of acute overdosage.
     
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