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MEPHEDRONE

House M.D.

New member
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4-Methylmethcathinone or Mephedrone is a β-ketoamphetamine belonging to the family of synthetic cathinones, an emerging class of designer drugs known for their hallucinogenic and psychostimulant properties, as well as for their abuse potential. Drugs from this class of compounds are known to produce central nervous system stimulation, psychoactivity and hallucinations. A research chemical first developed as an analogue of MDMA in 1929, it eventually became popular among recreational drug users between 2007 and 2009 as it became available for purchase online in dark markets.

BACKGROUND AND HISTORY.
According to the European Monitoring Centre for Drugs and Drug Addiction, Saem de Burnaga Sanchez first recorded the synthesis of mephedrone in a French medical journal in 1929. The substance remained an obscurity until 2003, when it was re-discovered by an underground chemist called ‘Kinetic’.
In Israel, a drug similar to mephedrone containing cathinone was sold legally from around 2004. The drug was called ‘hagigat’ and the Israeli government eventually banned it. The cathinone was modified (independently or possibly using Kinetic’s rediscovered formula) and the new legal product, mephedrone, was synthesised. A few budding entrepreneurs quickly scaled mephedrone production, and the drug was originally distributed by Israeli websites in capsule form and branded as Sub Coca or Neo-Doves. Israel had witnessed the first mass market in mephedrone. The drug was first made illegal here in 2008. Mephedrone was also cleverly marketed online through social media, dark forums and with advertisement appearing on the back of serious online news feeds. The true chemical formula of mephedrone remained hidden until it was revealed on an underground online forum. The secret was out and other countries quickly became involved in distribution, with the Chinese imitating the manufacturing process, and eventually taking over production. More competition drove the price down and increased the drugs' availability.

Dark market and street slang: Meph, meow, meow-meow, m-cat, plant food, drone, bubbles, kitty cat.

Pharmacy/recreational used: Neo-Doves pills.

LEGAL STATUS.
Mephedrone is a Schedule I stimulant under the Controlled Substances Act of US. Despite the re-classification of mephedrone as a Class B restricted substance by the United Kingdom and restrictive legislation by the United States, international policy regarding mephedrone control is still developing and interest in synthetic amphetamine-like drugs could drive the development of future mephedrone analogues.

European Union (EU).
In October 2010, a European Union commission called for an EU-wide ban of 4-methylmethcathinone.

Australia.
According to one contributor, a large bust in Cairns seized 2000 doses of 4-methylmethcathinone and was subsequently added to the Australian federal drug watch list and is now considered illegal if intended for human consumption.

Austria.
Austria reportedly banned 4-methylmethcathinone on Aug 20, 2010 in their SMG.

Belgium.
Belgium banned 4-methylmethcathinone on Apr 29 2010, by making it a regulated drug requiring the approval of the Ministry of Human Health to import, sell, or possess.

Brazil.
Brazil added 4-methylmethcathinone (mephedrone) to the list of Scheduled drugs (class F2), making it illegal to possess, sell, or manufacture without a licence as of August 2011.

China.
China has made 4-Methylmethcathinone a Category I psychotropic substance, illegal to sell, buy, import, export, and manufacture 4-methylmethcathinone as of September 2010.

Czech Republic.
The Czech Republic added a number of recent drugs to their controlled lists in early 2011, including BZP, 2C-I, PMMA, synthetic cannabinoids, and a variety of cathinone derivates including 4-methyl-methcathinone and MDPV. The Czech Republic has decriminalized possession of small amounts of most recreational drugs, so penalties for possession are quite low.

Denmark.
Denmark's Minister for Health and Prevention Jakob Axel Nielsen banned "mephedrone", "flephedrone" and ethylcathinone on Dec 18, 2008. As of July 1, 2012, Denmark also created a type of Analogue law that would include cathinones.

Finland.
Through the Medicines Act, 4-methylmethcathinone is classified as a "medicinal product", making it illegal to manufacture, import, possess, sell, or transfer it without a prescription.

France.
The french Ministry of Health decided in early June 2010 to add 4-Methylmethcathinone to the list of illicit substances.

Germany.
4-Methylmethcathinone has been added to Anlage I starting Jan 22, 2010 and will then be controlled in Germany.

India.
4-Methylmethcathinone seems to have been added to the list of controlled psychotropic substances sometime in 2014 but a few media outlets refer to the date as Feb or Mar 2015.

Israel.
In December 2007, 4-methylmethcathinone was added to Israel's list of controlled substances, making it illegal to buy, sell, or possess. Further, Israel banned four "families" of substances and their derivatives in July 2010. The families are cathinones, methcathinones, amphetamines, and methamphetamines.

Italy.
Listed in Tabella I of "Tabelle delle sostanze stupefacenti e psicotrope", making it illegal to possess, purchase, or sell.

Netherlands.
In March 2010, the Dutch Ministry of Health and the Medicines Authority IGZ informed the Ministry of Justice that they now consider Mephedrone an unregulated medicine and sales and distribution of it are now prohibited.

New Zealand.
Although one contributor stated that 4-methylmethcathinone was controlled in December 2008, this has been disputed by another visitor. We have been unable to find any documentation that it is controlled in New Zealand.

Norway.
The "Derivatbestemmelsen" is an Analog Act-type law in Norway that controls 4-methylmethcathinone, Bk-MBDB, Bromo-Dragonfly, 1,4butanediol, GBL, and MBDB.

Poland.
On Aug 25, 2010, 4-Methylmethcathinone was added to the list of controlled "psychotropic drugs" in the I-P group.

Romania.
4-Methylmethcathinone was added to Romania's list of controlled substances in February 2010.

Russia.
Methylone & Mephedrone are in List 1 in Russian Federation as if August 2010. This means it is illegal to manufacture, buy, possess, or distribute.

Slovak Republic.
Starting March 1, 2011, MDBD, bk-MBDB, bk-MDMA, and 4-Methylmethcathinone are controlled in the Slovak Republic.

Sweden.
Classified as a "health hazard" or "hazardous substance" ("hälsofarlig vara") pending further legislation, a ban on 4-methylmethcathinone went into effect on December 15, 2008, making its sale illegal. Use of 4-methylmethcathinone is not explicitly illegal under this regulation.

United Kingdom.
4-Methylmethcathinone is a class B drug, illegal to possess without the proper license or prescription, as of Apr 16, 2010.
PHARMACODYNAMICS AND NEUROCHEMISTRY.
Mephedrone reversibly changes the configuration of the dopamine transporter and there is a change in the transporter flow (DAT) and an increase in the concentration of dopamine in the inter synaptic space by activation of D2/D1/D3, but without affecting VMAT2. Serotonin stimulation remains subtle under the powerful pressure of dopamine, but is still present due to low-afin activation of 5-HT2A, 5-HT1A, 5-HT2C, 5-HT2B (SERT).
Mephedrone can be consumed for a long time because it is an inhibitor of dopamine reuptake (and serotonin), so mephedrone does not affect vesicular storage, but affects only the transfer of monoamines beyond the plasma membrane and our body in response changes the expression of receptors, protecting them from excessive chemical stimulation. All this explains the adynamic and demotivational state after chronic abuse of almost any psychoactive substances affecting DAT and SERT. DAT/SERT - 2.41.


Metabolites of mephedrone:
  • nor-mephedrone;
  • nor-dihydromephedrone;
  • 4-carboxy-dihydro-mephedrone;
  • hydroxytolyl-mephedrone;
  • nor-hydroxytolyl mephedrone.
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MAIN PHYSICAL EFFECTS.
Generally described as being more intense of a stimulant than MDMA, providing greater euphoria, but with somewhat less of an empathogenic feel and a shorter length to the 'rush.' It is often reported as very 'fiendish,' with the tendency to cause users to redose repeatedly throughout the experience.

Postive:
• Mental and physical stimulation;
• Euphoria, mood lift;
• Feelings of empathy, openness;
• Increase in sociability, desire to talk with others;
• Pleasurable rushing.

Neutral:
• General change in consciousness (as with most psychoactives);
• Decreased appetite;
• Pupil dilation;
• Unusual body sensations (facial flushing, chills, goosebumps, body energy);
• Change in body temperature regulation;
• Sweating;
• Increase in heart rate and blood pressure.

Negative:
• Strong desire to redose, craving to recapture initial euphoric rush;
• Uncomfortable changes in body temperature (sweating/chills);
• Heart palpitations, sense of racing heart;
• Impaired short-term memory;
• Insomnia;
• Tightened jaw muscles, grinding teeth (trismus and bruxia);
• Muscle twitching;
• Nystagmus;
• Dizziness, light headedness, vertigo;
• Vasoconstriction;
• When insufflated: pain and swelling in nose and throat, sinusitis.


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CLINICAL EFFECTS & PSYCHO-MANIFESTATIONS.
In case of an overdose, the limbs turn blue and there are signs such as chest pain and paranoia. Mephedrone is absolutely not suitable for chronic use, although it does not give a pronounced tolerance to neurotransmitters. Changes in the psyche are possible, but reversible. During use, memory suffers and mental status becomes paranoidal. It is also worth noting the effect of mephedrone on the skin and its appendages - due to the pronounced constant spasm of blood vessels, collagen synthesis decreases, which affects the skin visually. The cardiovascular system suffers from prolonged use of its resources due to mephedrone stimulation of adrenergic receptors, but mephedrone does not have direct cardiotoxicity due to metabolites such as MDMA or cocaine. The lack of side effects with low tolerance potential makes mephedrone a drug that causes severe dependence.

DOSAGE AND METHODS OF USE:
LD 50 for humans is equivalent to ≈ 120 mg/kg.

Oral:
Light: 50 – 100 mg.
Common: 100 – 200 mg.
Strong: 200 – 300 mg.

With the use of mephedrone orally, there are certain difficulties, which are more often reduced to the quality of the product. The only disadvantage of the method of use is that a lot of substance is required. It's all about cytochromes P450, which carry out the main metabolism of mephedrone and to achieve a threshold effect will require a slightly larger amount compared to the intranasal method. There are combinations of oral mephedrone with methylone, the "cousin" of MDMA. Such a combination can significantly reduce the consumption of mephedrone and thereby minimize intestinal side effects, as well as prolong the euphoric part of the trip.

Intranasal:
Light: 15 – 25 mg.
Common: 25 – 80 mg.
Strong: 80 – 125 mg.

The most common way to use mephedrone is intranasal. The dosage in users with an average tolerance to the substance is usually high and ranges from 250-400 mg. This method causes trauma to the nasal mucosa and gives serious discomfort sensations when consumed. The active effect of the substance is short, and the time of general action does not exceed more than 30 minutes in duration.

Intravenous:
Light: 50 – 100 mg.
Common: 100 – 300 mg.
Strong: 300 – 400 mg.
Overdose: 400 mg and bigger.

About 20% of mephedrone users take intravenously.

TRIP DURATION:

Oral.

Total: 2 – 5 hours.
Onset: 00:15 – 00:45.
Strongest: 01:00 – 02:00.

Intranasal:
Total: 1 – 3 hours.
Onset: ~00:05.
Strongest: 00:10 – 00:45.

Intravenous:
Total: 2 hours.
Onset: 30 seconds.
Strongest: 00:05 – 00:50.


INTERACTION
Metphedrone is metabolized by the liver enzyme CYP2D6, and the elimination half-life of mephedrone - 70 minutes. Peak plasma mephedrone concentration - 52 minutes.
✓ Cytochrome P450 2D6 (CYP2D6) is an enzyme that is encoded in humans by the CYP2D6 gene. CYP2D6 is mainly expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nistantia. CYP2D6, a member of the cytochrome P450 mixed oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Specifically, CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs by adding or removing certain functional groups, such as hydroxylation, demethylation, and demethylation. CYP2D6 also activates some prodrugs and metabolizes several endogenous substances such as hydroxytryptamines, neurosteroids, and m-tyramine and p-tyramine, which CYP2D6 metabolizes into dopamine in the brain and liver.

✓ Mephedrone does not convert to catechin metabolites, like MDMA and does not poison the body by free radicals of oxygen and nitrogen due to strong redox reactions in the process of metabolism.

It is not recommended combining with any other substances from this group: caffeine, Ritalin, amphetamine, cocaine, a-pvp and same types of drugs
It is not recommended combining with stimulating psychedelics: DO*, 25-Nbome, 2C*.
It is not recommended combining with painkillers, especially with tramadol
It is not recommended combining with antidepressants
It is not recommended combining with euphoretics: MDMA and MDA
It is not recommended with "slow" drugs - heroin, methadone, butyrates, alcohol.

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ADDICTION.
It has been established that there is a potential for the development of physical dependence in chronic abuse of mephedrone. Most of the symptoms that are associated with mephedrone withdrawal syndrome appear to be predominantly psychological in nature. Observing that a person has intermittent periods of extreme energy, sociability, friendliness, and even possible psychosis, followed by withdrawal symptoms, suggests a very serious case of drug abuse. There is no standard treatment plan specifically designed for mephedrone addiction and addiction, due to limited scientific knowledge of the substance. When using the drug, there is a feeling of general stimulation and euphoria, as well as improving mood and cognitive functions. The effects of the drug are produced as a result of how it affects the central nervous system, where patterns of movement and reward are controlled. How intense your symptoms will be correlated with how long you abuse the substance. There is no set timeline for avoiding mephedrone, but it is believed that there is a similarity with the withdrawal schedule of other stimulant drugs. The exact timeline will depend on the duration of use and dosage during chronic use.

Chronic mephedrone user habitus:
✓ Difficulty sleeping;
✓ Muscle contractions;
✓ Seeing and hearing things that aren’t there;
✓ Needing to use more mephedrone to get the same effect;
✓ Dependence;
✓ Financial and social problems.


Addiction symptoms:
  • Becoming lethargic and needing more sleep than normal;
  • An increase in appetite;
  • Apathy and depression;
  • Vivid dreams;
  • Cravings to use mephedrone;
  • Extreme weight loss;
  • Sudden crying;
  • Aggression;
  • Anxiety;
  • Nosebleeds;
  • Sniffing;
  • Rashes;
  • Nausea;
  • Headaches;
  • Mood swings.
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SUPPORT.
  • L-carnitine (levocarnitine) - 1000 mg an hour before taking mephedrone and 1000 mg after.
  • Alphalipoic acid - 250 mg an hour before the drug use and 250 mg after.
  • Vitamin C - 1000 mg once a day trip, and can also be within 3 days after in the same dosage.
  • L-tryptophan and L-tyrosine are aminoacids and precursors of serotonin and dopamine. Take once a day L-tyrosine 1000 mg in the morning, L-tryptophan 500-1000 mg in the evening 30 minutes before the expected sleep. Take within a three-week period, the beginning of the course is not earlier than 72 hours after the last use of euphoric stimulants.
  • Magnesium supplements. Use magnesium citrate. Daily dose of magnesium is 330 - 450 mg, but mephedrone decreases it.
OVERDOSE TREATMENT.

Risks:
  • Tachycardia and heart rhythm disturbances;
  • Gangrene;
  • Increased blood pressure hemorrhage in the brain;
  • Severe vasospasm: infarction and ischemic stroke;
  • Critical increase in body temperature;
  • Rhabdomyolysis (destruction of muscle fibers) and renal failure;
  • Convulsions and change in consciousness injury.
Symptoms:
  • Nausea and vomiting;
  • Profuse sweating and chills;
  • Involuntary contractions of the muscles of the body and face, grimaces;
  • Critical increase in body temperature (38-39 C);
  • Severe headache;
  • Pressing and burning chest pain;
  • Convulsions;
  • Loss of consciousness;
  • Heart rhythm disturbances;
  • Frightening hallucinations, panic and psychosis;
  • Respiratory and cardiac arrest.
FIRST AID.
  • Call for local emergency care.
  • Exclude any physical activity, lay down the patient with lowered lower limbs like a half-sitting position.
  • Ensure fresh air, remove constraining clothing, loosen the tie and unfasten the belt.
  • Measure blood pressure, pulse frequency and rhythm, body temperature. At high temperature, physical methods of cooling: Do not cover in a blanket, wipe the body with warm water.
  • In case of convulsions: Try to turn the patient on his side, hold his head with your hands to avoid injury. It is strictly forbidden at the time of a convulsive seizure: Try to mouth the patient, unclench the jaw, stick out the tongue.
  • Upon onset of clinical death, CPR is performed.
Drugs of primary choice - benzodiazepines by priority:
  • Diazepam - 10 -15 mg under the tongue (Neorelium, Valium, Stesolid)
  • Clonazepam - 1 mg under the tongue
  • Nitrozepam - 10 mg under the tongue (Mogadon, Imeson, Novanox)
High blood pressure and chest pain:
  • Labetalol 100 - 200 mg (Ipolab, Ascool, Labenon, Betarl, Trandate)
Very frequent and irregular heart rate:
  • Metoprolol 25 mg - under the tongue (Lopressor, Metodura, Prelis, Apo-Metoprolol, Egilok)
The use of non-selective beta-blockers to cut heart rate is not recommended.
 
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