|Year : 2015 | Volume
| Issue : 2 | Page : 55-58
Roar of meow-meow (mephedrone) in India
Pooja Yudhishthir Palkar1, Anand Ajit Kumthekar2
1 Rural Medical College of Pravara Medical Trust, Loni, Ahmednagar, Maharashtra, India
2 Jacobi Medical Center, Albert Einstein College of Medicine, New York, USA
|Date of Web Publication||20-Jan-2016|
Pooja Yudhishthir Palkar
No. 49, Yuneela, Pramathesh Society, Near Mahatma Society, Kothrud, Pune - 411 038, Maharashtra
Source of Support: None, Conflict of Interest: None
Recently, a dangerous new designer drug mephedrone has fast gained popularity among the youth and teens of India. Its abuse has soared to mount to an epidemic. It has psychoactive properties and is believed to bring about effects similar to the use of cocaine, amphetamine, and 3,4-methylenedioxy-N-methylamphetamine. The aim of this review is to discuss how mephedrone acts, health risks with its use and its emergence in India. The past and the emerging PubMed and Internet literature on mephedrone, and synthetic cathinones are reviewed. Recent studies suggest that use of synthetic cathinones lead to not just serious psychiatric but serious neurological, cardiovascular, and sexual health sequelae as well. Use of these designer drugs may lead to multi-organ failure and death. It has become increasingly evident that mephedrone is highly dangerous to public health. This warrants educating and training healthcare providers to provide optimum management.
Keywords: Designer drugs, mephedrone, psychostimulant, synthetic cathinones
|How to cite this article:|
Palkar PY, Kumthekar AA. Roar of meow-meow (mephedrone) in India. J Mental Health Hum Behav 2015;20:55-8
| Introduction|| |
Designer drugs have been a menace in the developed countries, and they have slowly trickled down to the developing countries. There has been a significant rise in the number and variety of designer drugs, and this has a significant impact on the understanding and management of drug abuse. Synthetic cathinones are a naturally occurring b-ketone amphetamine analog found in the leaves of Catha edulis (khat plant). At least 12 different types of synthetic cathinones are described, of which mephedrone and 3,4-methylenedioxypyrovalerone (MDPV) are most commonly used. The recreational drug scene in India is raging with mephedrone since its arrival in India in 2013. It goes by street names "Meow-Meow," "Drone," "M-Cat," "White Magic," "methylmethcathinone (MMC) hammer," "Rush," and "Bubbles." It is a lot cheaper than cocaine, selling for as little as Rs. 150/g versus Rs. 3000/g for cocaine.  It is available easily from street dealers and can also be ordered online through internet pharmacy websites and is delivered to the doorstep. Mephedrone, manufactured in India and China, is marketed as plant feed or bath salts on the internet but is being widely used as a narcotic drug.  Israel was the first to ban it in 2008, followed by the UK in 2010 and the US in 2011.  Initially, the drug was not on the list of banned drugs in India but was included in the list in March 2015. Mephedrone appears to be used by several population groups, including people involved in the dance and music scene as well as mainstream young adults and adolescents.  According to one report, almost 8 out of 10 drug addicts in Mumbai city are using this cheap party drug.  The questionable legal status, easy availability, low prices, high purity of mephedrone, and the unreliable purity of other drugs are some of the other factors that exponentially increased the demand for mephedrone. ],[],[ Recent studies indicate that this rise in popularity is not directly linked to any decreased use of ecstasy or cocaine; rather, instead of replacing or displacing these drugs, mephedrone appears to have been added to the established repertoires of psychostimulant narcotics. ,
| Pharmacology|| |
Mephedrone is a synthetic ring-substituted cathinone closely related to the phenethylamine family, differing only by a keto functional group at the beta carbon. Chemically, it is 4-MMC, and its formula is C 11 H 15 NO. As it is a cathinone derivative with affiliation to beta-keto amphetamines, mephedrone is expected to act as a central nervous system stimulant by promoting the release of monoamine neurotransmitters and likely inhibiting their reuptake. ,,, Indeed, in vitro studies on the effects of the cathinone derivatives methcathinone and methylone confirm that the main mechanism of action is very similar to that of amphetamine, therefore being characterized by a predominant action on plasma membrane catecholamine transporters.  Both amphetamines and cathinones bind to noradrenalin, dopamine, and serotonin transporters, each of them differing from each other by its relative binding potency.  In particular, the presence of the ring substituent on the phenethylamine core modifies the pharmacological properties by giving the compound some 3,4-methylenedioxy-N-methylamphetamine (MDMA)-like effects, whereas amphetamines and cathinone derivatives without ring substituents exert mostly stimulant effects.  Cathinones' potencies are mostly lower than those of amphetamines as beta-keto amphetamines show a reduced ability to cross the blood - brain barrier due to the presence of the beta group. ,
N-demethylation to the primary amine, reduction of the keto moiety to the respective alcohol, and oxidation of the tolyl moiety to the corresponding alcohols and the carboxylic acid is the major metabolic pathway for mephedrone, followed by N-dealkylation. Intake of both mephedrone and other beta-keto amphetamines can be detected with appropriate urine testing technology. ,
| Routes of Administration, Dosage, and Co-Abuse|| |
Mephedrone comes in capsules, tablets or white powder that the users can swallow, snort, smoke, inject, or use rectally. The most common routes for recreational use include insufflation (snorting) and oral ingestion. Because of its solubility in water, mephedrone is reportedly used by rectal administration (dissolved in an enema or within gelatine capsules) as well or injected intravenously. When snorted, mephedrone elicits its effects within a few minutes, with the peak being reached in <30 min followed by a rapid comedown. The desired effects last approximately 2-3 h; this leads users to redose during a single session to extend the duration of the desired effects.  According to online users' advice, mephedrone dosage for snorting may range between 25 and 75 mg, with the lower threshold being 5-15 mg and with a level in excess of 90 mg to be considered a high dosage.  Dosing is more frequent when taken intranasally; this route is allegedly associated with greater abuse liability than the oral route. , Other typical methods of intake include oral administration, through ingestion of capsules or tablets; swallowing mephedrone powder wrapped up in cigarette paper (bombing); or mixed with water.  On average, the most common oral dosages are higher than the snorting ones, being in the range between 150 mg and 250 mg.  Time of onset may be of 45 min 2 h and may vary in association with the amount of food contained in the stomach. Due to this, users suggest to take mephedrone on an empty stomach. With oral administration, psychoactive effects may last longer (up to 2-4 h); side effects might be milder and the urge to redose less pressing. Some consumers exploit both insufflation and oral ingestion in combination to achieve both faster onset and long-lasting effects.  The low oral bioavailability of mephedrone, around 10%, may explain why insufflation is the preferential route of administration.  With respect to oral ingestion, users report that rectal administration is characterized by the faster onset of the effects and requires lower doses, for example, 100 mg on average.  Although not typically advised, because this may increase the drug addictive liability levels, mephedrone may also be injected either intramuscularly or intravenously, at one-half or two-thirds of the oral dose. , This method of intake appears to be fairly well-known in Romania where mephedrone may be combined with heroin.  Because of the capability of the drug to induce tolerance upon repeated doses, an increasing number of user reports have stated a quick progression to either regular drug use and/or uncontrolled bingeing behavior (known as "fiending"), with 1-4 g of mephedrone consumed in a session to prolong the duration of its effects. , A survey carried out by a drug-related website has unveiled an average monthly use of 11.16 g for each mephedrone consumer.  In a survey carried out in Scotland in February 2010, roughly one out of six users' surveyed reported "addiction or dependence" symptoms associated with their mephedrone use.  According to web users, mephedrone may be taken in combination with a number of stimulants, sedatives, and psychedelics.  These may include: Cocaine, amphetamine, modafinil, butylone, MDPV, methylone (combination being known as "Bubbles"), metamfepramone, alcohol, gammbutyrolactone/gamma hydroxybutyrate benzodiazepines, kratom (mytraginin), heroin, cannabis, ketamine (combination being known as "challenge"), MDMA, 1-Benzylpiperazine, 3-trifluoromethylphenylpiperazine, dimethylamylamine, and sildenafil.
| Adverse Effects|| |
Mephedrone is used for its stimulant and entactogenic properties. Consumption of synthetic cathinones result in typical stimulant-related subjective effects like increased alertness, awareness and energy, euphoria, sociability and talkativeness, intensification of sensory experiences, sexual arousal, reduced appetite, and insomnia. ,,, Users report that subjective effects of mephedrone are more similar to those of MDMA as compared with those of cocaine.  Some users described a strong craving to repeat or increase doses after taking mephedrone. ,, Mephedrone induces stronger feelings of craving in comparison with MDMA and users who snort mephedrone rate it more addictive than cocaine. , Commonly reported adverse effects of mephedrone use include altered mental status (agitation, paranoid delusions, hallucinations, panic attacks, self-mutilation, suicide attempts, and homicidal activity), irritability, inability to concentrate, short-term memory deficits, tachycardia, hypertension, chest pain, hyperthermia, diaphoresis, bruxism, nasal irritation, and nosebleeds from insufflation of the powder, tremors, seizures, dilated pupils, blurred vision, dry mouth/thirst, vomiting, anorexia, weight loss, cardiac arrest, and death. ,,, In addition, several other effects may be associated with intoxication by cathinones, including hyponatremia, hyperkalemia, metabolic acidosis, acute kidney injury and urinary retention, rhabdomyolysis, compartment syndrome, acute liver failure, cardiomyopathy, disseminated intravascular coagulation, catatonia, necrotizing fasciitis, and serotonin syndrome. ,,,,,,,,,,,, The development of craving, tolerance, dependence, and withdrawal syndrome was observed after the frequent consumption of high doses of mephedrone or MDPV. ,, Several cases of deaths related to the recreational use of synthetic cathinones have been reported worldwide over the last few years. ,,,, Recently, a significant increase of mephedrone use has been reported among men who have sex with men, ,, who use the drug solely to facilitate sex and has alarming health consequences such as increased spread of HIV and other sexually transmitted infections. There are large numbers of HIV-positive men in this subpopulation, the majority of whom share needles to inject and have unprotected sex with several partners. ,
| Management|| |
People with underlying cardiac, neurological and psychiatric conditions, especially those on medication, are likely to be at greatest risk of serious adverse events with the use of mephedrone.  Treatment for patients intoxicated with synthetic cathinones is mostly supportive care. Intravenous fluids should be initiated if the signs of dehydration are evident and measures to actively cool patients be taken if they have hyperthermia. It is critical to control agitation as rhabdomyolysis and cardiovascular collapse from excitatory delirium can occur.  While stimuli reduction may be of benefit, benzodiazepines, such as lorazepam or diazepam should be the first line agents in trying to sedate these patients and manage seizures. , When benzodiazepines do not have the desired effect, antipsychotics such as haloperidol can be an effective alternative to treat agitation, aggression, or psychosis in conjunction with benzodiazepines and it is important to keep in mind that severely agitated patients are at risk of sudden death.  In the events of hypertension, in addition to benzodiazepines, further control of blood pressure can be achieved with alpha-adrenergic receptor antagonist, i.e., doxazosin.  If the patient presents with coronary ischemia, routine protocol treatment with nitroglycerin, morphine, and antiplatelet drugs should be considered. However, a beta blocker is contraindicated which may worsen hypertension, and coronary vasoconstriction and treatment of hypotensive episodes should be with a direct acting vasopressor, for example, phenylephrine.  Other conditions that may mimic sympathomimetic excess such as thyroid storm, neuroleptic malignant syndrome, intracranial hemorrhage and antimuscarinic toxicity could all present in a similar fashion and should be considered and ruled out. Those individuals presenting with less severe symptoms should be assessed and managed as for any other users of psychoactive drugs and may simply need reassurance, support, and observation. Both, a brief motivational intervention and appropriately adapted psychosocial intervention have been suggested to treat mephedrone addiction. 
| Conclusion|| |
Studies suggest that use of synthetic cathinones leads to not just serious psychiatric but also serious neurological, cardiovascular and sexual health sequelae. The use of these designer drugs has the potential to lead to multiorgan failure and death. The inexpensive nature, desired psychostimulant effects, and the purity are some of the factors that have contributed to its rise in India along with its aggressive online marketing and easy availability on the streets. India appears to be an emerging market for synthetic cathinones leading to multiple social and financial issues. It has become increasingly evident that mephedrone is highly dangerous to public health which warrants educating and training healthcare providers. Mephedrone should be included in clinical and forensic toxicology screenings, which will help in early detection, optimum management, and prevention of dangerous complications associated with its use. Additional research studies are required to gauge the actual burden of mephedrone abuse on public health in India.
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Conflicts of interest
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