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WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences SJIF Impact Factor 5.210 Volume 4, Issue 08, 297-336. Review Article ISSN 2278 – 4357

DESIGNER : A REVIEW

Dr. Suyash Chavan,MBBS*1 and Dr. Vandana Roy2

1MD, Resident Doctor, Department of , Maulana Azad Medical College, New Delhi. 2MD, PhD Professor, Department of Pharmacology, Maulana Azad Medical College, New Delhi.

ABSTRACT Article Received on 25 May 2015, Designer drugs‟ are psychoactive substances that mimic the effects of

Revised on 16 June 2015, other banned illicit drugs but evade detection by law enforcing Accepted on 07 July 2015 agencies. This is because of modifications in the structure of the

original psychoactive molecule. Originally developed as a way to *Correspondence for evade existing laws in the late 1960s, the synthesis and use of

Author designer drugs has increased dramatically. They are advertised with Dr. Suyash Chavan innocuous names and are sold mostly over the internet, discreet outlets MD, Resident Doctor, Department of and at entertainment clubs. Victims may exhibit symptoms similar to Pharmacology, Maulana the effects of the illegal drug that these synthetic drugs mimic, Azad Medical College, however, the exact culprit drug is not detected due to structural New Delhi. modifications in the new drug. Overdose of these drugs may lead to

serious adverse effects that can be life threatening. Understanding the

pharmacology and toxicology of these agents is essential to facilitate their detection and to

provide better medical care for patients suffering from adverse effects due to their

consumption. This review focuses on designer drugs, their pharmacology and clinical effects based on the literature available. Multiple names under which these drugs are commonly marketed are identified and tabulated.

KEYWORDS: Designer drugs, New Psychoactive substances, Psychostimulants, Synthetic drugs, , Legal highs.

1. INTRODUCTION Drugs have been used for recreational purposes since time immemorial. Addicting potential and the propensity to harm has led to a ban on many of these drugs. To circumvent the ban,

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new compounds are being developed that are similar in effect to the banned drugs but are slightly different in their chemical structure so that they can escape detection in the standard drug tests. These drugs are commonly known as designer drugs or new psychoactive substances.[1]

“Designer drugs” have been defined as “Substances that have been developed especially to avoid existing drug control measures and are manufactured by making a minor modification to the molecular structure of controlled substances, resulting in new substances with pharmacological effects similar to those of the controlled substances.”[2]

Designer drugs have also been defined as “Substances designed to mimic the effects of known drugs by slightly altering their chemical structure in order to circumvent existing controls.”[3]

2. HISTORY The use of drugs for non-medical purposes can be traced back to the early history of mankind. Around 1000 A.D. the application of distillation techniques to ferment beverages resulted in a much more potent product. In the mid-1800s, was isolated from opium and was synthesized from morphine. In the early 1900s, was isolated from cocoa leaf. The use of these purified, more potent materials for non-medical uses soon followed. In the past century, research on synthetic drugs has led to an epidemic of newer drugs of abuse.[4]

Realizing that the drugs were being used more for non-medical purposes, the Second International Opium Convention in 1925 banned the recreational use of morphine and heroin. This ban led to a rapid rise in the designing of new drugs for recreational purposes.[5]

The introduction of pharmaceuticals with psychoactive properties for example, and into clinical practice, soon led to their abuse. As abuse of these compounds increased, controls on production, distribution, and their use were tightened. A number of clandestine laboratories started appearing to meet the demand of the illicit market. In the 1960s, lysergic diethylamide (LSD) was produced as a research chemical. Its hallucinogenic properties, made it popular among youngsters as a club drug. The ban on LSD led to development of new compounds with similar effects by a slight modification in the molecular

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structure of LSD. This structural modification increased their potency and prevented them from being detected in drug tests.[6]

The anaesthetic agent emerged as a new club drug (angel dust) during the 1970s. structure based new Opioid drugs, Anabolic steroids and drugs like analogues were developed in the 1980s and 1990s. Simultaneously their designer versions were also developed.

Throughout the 1960s and 1970s as governments started curtailing the import of natural products (cannabis, morphine etc) the number of illicit laboratories producing these banned drugs and the diversion of pharmaceuticals in the production of such drugs increased.

In the past few years there has been a rapid increase in the research, manufacture and trade of new designer drugs. In recent times, synthetic , synthetic , and have emerged as new designer products in the illicit market.[7]

3. GLOBAL PROBLEM Notwithstanding the controls put by many agencies throughout the world on the manufacture and sales of designer drugs, the number of designer drugs and related research chemicals reported to United Nations Office For Drug Control(UNODC) have risen from 166 at the end of 2009 to 251 by mid-2012.[8] United Nations Office on Drugs and Crime estimates that about 230 million use an illegal drug at least once a year and the use of designer drugs is rapidly increasing.[9]

Designer Drug use is prevalent all over the world. North America remains the biggest illicit drug market in the world, as well as the region reporting the highest drug-related mortality rate. According to figures approximately 1 in every 20 deaths among persons aged 15-64 in North America is related to drug abuse.[10]

In Europe, the number of notifications of new psychoactive substances (another name for designer drugs) received by the The European Monitoring Centre for Drugs and Drug Addiction centre (EMCDDA) averaged five per year from 2000 to 2005. This had increased to 49 by 2011, indicating that a new psychoactive substance was introduced in the European market almost every week.[11]

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Asia and Africa are emerging as centres for the production and trafficking of illicit substances including newer designer drugs that substitute the illicit drugs banned in developed countries. Precursor chemicals are diverted into drugs that mimic the effect of illegal drugs. Legal drugs like ephedrine and pseudoephedrine are transported from India and Asian countries to Africa which serves as a transit junction for manufacture of -type and their trade to European countries. Codeine-based cough syrups, , benzodiazepine, buprenorphine and are the preparations most commonly diverted for the manufacture of new designer drugs.

Every country‟s drug habits depend upon international drug trade and trends of the surrounding area. In 2007, India was named one of the 20 major hubs of illegal drug traffic along with a number of its neighbouring countries, Pakistan, Afghanistan and Myanmar in the East. According to the 2010 annual report of the International Narcotics Control Board (INCB), India is fast becoming a popular destination for abusers. India is one of the main sources of psychotropic substances sold throughout illegal internet pharmacies.[12] At the last national survey in 2000-01 there were 70 million drug users in India. Among those treated for drug problems in India in 2010, 66 % abused (33 % heroin, 14 % opium and 19 % prescription opioids), 22 % abused cannabis and 12 per cent other substances which includes the newer designer drugs. The use of synthetic drugs grew to account for 15% of reported users in recent times. Designer drugs are gaining popularity and are likely to be one of the major causes of drug related morbidity and mortality in India in the near future.[13]

4. CATEGORIES OF DESIGNER DRUGS These include drugs belonging to various pharmacological classes that have been modified for abuse. The various classes to which these drugs belong can be as follows.[14] 1. Opioids 2. Cannabinoids 3. Drugs for erectile dysfunction 4. Anabolic steroids 5. Psychedelics 6. 7. -based 8. Stimulants

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Nomenclature Based upon the chemical structure, the drugs have been given names by the IUPAC (The International Union of Pure and Applied ). However these drugs are more commonly known by the names given by the illicit drug dealers. For example, Alpha Methyl Fentanyl, the designer variant of the Opioid drug Fentanyl has an IUPAC name of N-phenyl- N-[1-(1-phenylpropan-2-yl)-4-piperidyl]propanamide and is commonly known as “China white”(Table-1-10).

Chemical structure & Pharmacology Available scientific information about designer drugs is limited.

Opioids – These are synthetic drugs that resemble morphine or other opiates in pharmacological effects. Opioids work by binding to opioid receptors, which are found principally in the central and peripheral nervous system. They produce a sense of wellbeing or euphoria that can lead to their addiction. Tolerance develops to the euphoric action of opioids and addicts are at a high risk of overdose, which can result in fatal respiratory depression.[15] Details of the various synthetic, designer versions of opioids are shown in (Table 1).

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Table 1: Designer Drugs - Opioids Pharmacokinetics Iupac Name Common Discovery And Historical Designer Drug Pharmacodynamics and Adverse Chemical Structure Name Aspects Effects Highly potent long acting drug. N-phenyl-N-[1-(1- The α-methyl group prevents binding to First identified in two drug ALPHA METHYL phenylpropan-2-yl)-4- metabolic enzymes. China white overdose victims in FENTANYL piperidyl]propanamide [16] It has high addiction potential. 1979 C23H30N2O Overdose can lead to severe respiratory [17] depression (RS)-N-(3-methyl-1- Discovered in 1974. 3-Methylfentanyl is more potent than phenethyl-4-piperidyl)-N- 3-Methylfentanyl was the drug 3-METHYL Fentanyl. phenyl-propanamide reported to have been used in FENTANYL Overdose can lead to deaths among the Moscow theatre hostage [19] [18] opiate addicts C23H30N2O crisis in 2002 N-(4-fluorophenyl)-N-[1-(2- It is more potent than fentanyl and has phenylethyl)piperidin-4- PARAFLUOROFEN Para-fluorofentanyl emerged as a similar adverse effects. Respiratory yl]propanamide TANYL drug of abuse during 1980s depression due to overdose can be life

threatening. C22H27FN2O It is the reversed ester of pethidine and is less potent than morphine 1-Methyl-4-phenylpyridinium (MPP+) ( 1-Methyl-4-phenyl-4- is a metabolite of MPTP. propionoxypiperidine) It leads to rapid onset of symptoms MPPP Desmethylprod similar to Parkinson's Disease. Glial C H NO ine 15 21 2 cells contain the enzyme MPP+ which

metabolizes MPTP to the neurotoxin

MPP+. This selectively damages brain tissue in the substantia nigra and causes Parkinsonian symptoms[20,21]

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1-[2-(4-chlorophenyl)ethyl]- Methopholine is 4'- 6,7-dimethoxy-2-methyl- an opioid analgesic NITROMETHOPHO 1,2,3,4- drug. The adverse effects includes ophthalmic Versidyne LINE tetrahydroisoquinoline It was discovered by Swiss side effects, corneal opacities, blindness. researchers at Hoffmann-La

C20H24ClNO2 Roche in 1950s 3-[2-(1-Amino-1- It leads to confusion, dizziness, methylethyl)-1- O-Desmethyltramadol respiratory depression and seizures. O-DESMETHYL hydroxycyclohexyl]phenol Krypton (O-DT) is the main active Overdose related accidental deaths can metabolite of tramadol occur due to severe respiratory [22] C15H23NO2 depression. Effects are similar to Heroine. It has 4,5-α-Epoxy-17- It is an opiate analogue invented high addiction potential. The effects last methylmorphinan in the USA in 1932. one and a half hours. Withdrawal DESOMORPHINE -3-ol Krokodil Simple synthesis from codeine symptoms can occur in long term users. led to increased clandestine It produces severe tissue damage and [23] C17H21NO2 production of Desomorphine. gangrene and can lead to limb amputation.[24]

Cannabinoids - are chemicals that mimic the effect of Tetra hydro cannibinol – one of the main active principles in cannabis. The receptor agonists mimic the effects of anandamide, the endogenous cannabinoid, by interacting with

the CB1 receptor in the brain. Like cannabis, herbal mixtures containing synthetic cannabinoids are most often smoked. The cannabinoids can produce euphoria, tranquillity, mood changes, altered perceptions of time and space and of one's bodily dimensions, increased appetite, heightened sensory awareness and pleasure. These effects can lead to psychological dependence. The cannabinoids are added to a mixture of dried plant matter and sold under brand names such as Kronic, Spice and K2 (Table 2).

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Table 2: Designer Drugs- Cannabinoids PHARMACOKINETICS DESIGNER IUPAC NAME DISCOVERY AND COMMON NAME ,PHARMACODYNAMIC AND ADVERSE DRUG CHEMICAL STRUCTURE HISTORICAL ASPECTS EFFECTS (R)-(1-((1-methylpiperidin-2- It is a potent agonist at the cannabinoid yl)methyl)-1H-indol-3- receptor CB [25] AM-1220 1 yl)(naphthalen-1-yl)methanone It leads to feelings of euphoria and relaxation

It can cause heaviness, lethargy, tremors,

C26H26N2O vomiting, anxiety, palpitations Onset of action is 1 hr and action lasts for 1-2 hours

1-[(5-fluoropentyl)-1H-indol-3- Effects include feelings of euphoria, relaxation AM-2201 yl]-(naphthalen-1-yl)methanone ,laughter, enhancement of colours.[26]

C24H22FNO Side effects include dry mouth, ,dizziness, increase in appetite, lethargy, paranoia, psychosis and delusional thoughts [27] 5-(3-(1-naphthoyl)-1H-indol-1- AM-2232 yl)pentanenitrile

C24H20N2O 1-pentyl-2-methyl-3-(1- Feelings of euphoria. JWH-007 It was discovered by John W naphthoyl)indole It can cause red eyes, cotton mouth, loss of Huffman [28] C25H25NO balance and coordination (2-Methyl-1-propyl-1H-indol-3- JWH-015 It was discovered and named yl)-1-naphthalenylmethanone after Dr. John W. Huffman C23H21NO Naphthalen-1-yl-(1-butylindol-3- Detection by ultra-performance liquid JWH-073 yl)methanone "Forest Humus" chromatography–tandem mass spectrometry [29] C23H21NO method JWH-018 Naphthalen-1-yl-(1-pentylindol- "Legal cannabis herbal

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3-yl)methanone incense blends"[30] C24H23NO 4-methoxynaphthalen-1-yl-(1- JWH-098 pentyl-2-methylindol-3-

yl)methanone C26H27NO2 4-ethylnaphthalen-1-yl-(1- "herbal" synthetic Named after Dr. John W. JWH-210 pentylindol-3-yl)methanone cannabis products[31] Huffman C26H27NO (1-(2-morpholin-4-ylethyl)indol- It was invented by the JWH-193 3-yl)-4-methylnaphthalen-1- pharmaceutical company

ylmethanone Sanofi-Winthrop in the early C26H26N2O2 1990s (1-(2-morpholin-4-ylethyl)indol- JWH-200 3-yl)-naphthalen-1-ylmethanone

C25H24N2O2 (1-(5-fluoropentyl)-1H-indol-3- First identified by laboratories yl)(4-methyl-1-naphthalenyl)- in the Netherlands and MAM-2201 methanone Germany in June 2011 as an

ingredient in synthetic cannabis C25H24FNO smoking blends

Drugs for Erectile Dysfunction - These are synthetic chemical compounds that are structural analogues of . Sildenafil is phosphodiesterase 5 inhibitor that is prescribed for men with erectile dysfunction. The synthetic variants are found as an adulterant in a variety of supplements sold as "natural" or "herbal" sexual enhancement products (Table 3)

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Table 3: Designer Drugs- Drugs For Erectile Dysfunction DISCOVERY PHARMACOKINETICS DESIGNER IUPAC NAME AND PHARMACODYNAMIC COMMON NAME DRUG CHEMICAL STRUCTURE HISTORICAL AND ADVERSE ASPECTS EFFECTS 5-(5-(((3R,5S)-3,5-Dimethylpiperazin- First reported in Phosphodiesterase type 5 1-yl)sulfonyl)-2-ethoxyphenyl)-1- "Herbal" sex enhancement products 2003; synthetic inhibitor methyl-3-propyl-1H-pyrazolo[4,3- compound;

d]pyrimidin-7(4H)-one MasXtreme[32] structural

C23H32N6O4S analog of sildenafil ; 5-[2-Ethoxy-5-[2-(4-ethyl-piperazin-1- yl)-acetyl]-phenyl]-1-methyl-3-propyl- Hongdenafil is a Phosphodiesterase type 5 Acetildenafil 1,6-dihydro-pyrazolo[4,3-d]pyrimidin- synthetic analogue inhibitor 7-one of sildenafil[33]

C25H34N6O3

"Natural" sexual enhancement products [34] eg 5-(5-(((3R,5S)-3,5-Dimethylpiperazin- Libidinal, Maxyte, Mojo, Erex, Monster 1-yl)sulfonyl)-2-ethoxyphenyl)-1- First reported in Excyte, OMG, OMG45, Aziffa, Eyeful, Phosphodiesterase type 5 methyl-3-propyl-1H-pyrazolo[4,3- 2005[35] Hard Drive, Prolatis, Stiff Nights, inhibitor d]pyrimidine-7(4H)-thione Straight Up, Verect, WOW, Xaitrex, C H N O S 23 32 6 3 2 Xytamax, Red Magic, Size Matters, Zilex (with Golden Spear), and Zotrex. It is a prodrug and it 2-[(5-[5-(3,5-dimethylpiperazine-1- releases Phosphodiesterase sulfonyl)-2-ethoxyphenyl]-1-methyl-3- type 5 Nitrosoprodenafil propyl-1H-pyrazolo[4,3-d]pyrimidin-7- Herbal Mutaprodenafil and nitroprodenafil inhibitor aildenafil and yl)oxy]-N-methyl-N-nitroso-1,3- products free . thiazol-5-amine Adverse effects include C H N O S 28 38 8 5 2 Liver toxicity

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Anabolic steroids – Anabolic steroids are drugs that have similar effects to in the body. They are used therapeutically to stimulate bone growth and appetite, induce male puberty and treat chronic wasting conditions, such as cancer and AIDS. Adverse effects include harmful changes in cholesterol levels, liver damage and conditions associated with hormonal imbalance such as gynecomastia and testicular atrophy. Anabolic steroids are used in sports and bodybuilding as performance-enhancing drugs. Their use is banned by all major sporting bodies and drug control agencies. In order to avoid detection of such performance enhancing drugs by Anti-doping agencies, new synthetic anabolic steroids are being developed. (Table 4)

Table 4: Designer Drugs- Anabolic Steroids PHARMACOKINETIC IUPAC NAME DISCOVERY AND S STREET DESIGNER DRUG CHEMICAL HISTORICAL PHARMACODYNAMI REMARKS NAME STRUCTURE ASPECTS C AND ADVERSE EFFECTS Oral, Intramuscular It is a highly potent agonist for High affinity to (13S,17S)-13,17- the and progeste the androgen diethyl-17-hydroxy- rone receptors receptor and 1,2,6,7,8,13,14,15,16, Adverse effects include Tetrahydrogestrinone Developed by Patrick 17- THG infertility in both men and receptor. Closely Arnold decahydrocyclopenta women, related to the [a]phenanthren-3-one immunosuppresion, banned anabolic C21H28O2 acne, hirsutism. Abused steroids gestrinone by athletes for and trenbolone performance enhancement[36]

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Developed in 1966 13-Ethyl-17- by Wyeth Laboratories. hydroxy-18,19- Used to encourage weight Norboletone dinorpregn-4-en-3- The Clear gain and for the treatment

one of short stature. Detected

C21H32O2 in urine tests in athletes in the early 2000s[37] Increased muscle mass, performance enhancement[38] 17β-Hydroxy- Dose 10-20 mg/day and 2α,17α-dimethyl-5α- Superdrol, methasteron, titrated upwards. It is Methasterone androstane-3-one and methyldrostanolone metabolised by the liver C21H34O2 and is hepatotoxic. It can lead to decreased libido ,infertility, hot flushes, backache. (5S,8R,9S,10S,13S,1 4S,17S)-10,13,17- Route: Oral, IM, trimethyl- Transdermal 1,4,5,6,7,8,9,11,12,14 An . It was Desoxymethyltestosterone ,15,16- Madol one of the first "designer dodecahydrocyclope steroids" to be marketed as nta[a]phenanthren- a performance-enhancing 17-ol drug. It is hepatotoxic.[39] C20H32O

Psychedelics - Psychedelic drugs alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as . They produce effects similar to Lysergic Acid Diethylamide (LSD). The includes a trance-like state, meditation, dreaming and even near-death experience. These drugs can produce psychological dependence in the users (Table-5,6,7)

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Table 5 : Designer Drugs-Psychedelics (Lysergamide Based) DISCOVERY AND PHARMACOKINETICS DESIGNER IUPAC NAME COMMON HISTORICAL PHARMACODYNAMICS REMARKS DRUG CHEMICAL STRUCTURE NAME ASPECTS AND ADVERSE EFFECTS (6aR,9R)-4-acetyl-N,N-diethyl- 7-methyl-4,6,6a,7,8,9- It was originally hexahydroindolo[4,3- Orange ALD-52 discovered by Albert fg]quinoline-9-carboxamide Sunshine Hofmann

C22H27N3O2 (6aR,9R)-N,N-diethyl-7-ethyl-

4,6,6a,7,8,9- ETH-LAD is a hallucinogenic Slightly more potent ETH-LAD hexahydroindolo-[4,3- Described by Alexander drug similar to LSD[40] than fg]quinoline-9-carboxamide Shulgin LSD C21H27N3O As potent as LSD (8β)-N,N-Diethyl-6-propyl- Described by Alexander itself with an active PRO-LAD is an analogue PRO-LAD 9,10-didehydroergoline-8- Shulgin in the dose reported at of LSD carboxamide book TiHKAL between 100 and 200 micrograms. (8β)-6-Methyl-N-[(1R)-1- methylpropyl]-9,10- Lysergic acid 2- Developed by Richard didehydroergoline-8- butyl amide LSB Pioch at Eli Lilly in the carboxamide 1950s C20H25N3O

(8β)-8-{[(2S,4S)-2,4- Developed by the team Lysergic acid 2,4- Dimethylazetidin-1- led by David E. dimethylazetidide yl]carbonyl}-6-methyl-9,10- LSZ Nichols at Purdue didehydroergoline University. C21H25N3O

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Table 6: Designer Drugs- Psychedelics ( Based) IUPAC NAME DISCOVERY AND PHARMACOKINETICS COMMON DESIGNER DRUG CHEMICAL HISTORICAL PHARMACODYNAMIC REMARKS NAME STRUCTURE ASPECTS AND ADVERSE EFFECTS Alexander Shulgin Route: oral, nasal insufflation is discovered -C and painful. 2,5-dimethoxy-4- 2C-C described it in his book Effects last - 4 to 8 hours. chlorophenethylamine C H ClNO PIHKAL The visual effects of 2C-C are 10 14 2 (phenyletylamines I similar to LSD.[41] have known and loved) First synthesized in 1-(2,5-Dimethoxy-4- 1970 by a team from Route: oral, insufflation. 2C-D methylphenyl)-2- the Texas Research It boosts the waning action of C H NO aminoethane 11 17 2 Institute of Mental other drugs. Sciences It is a colourless substance. 2,5-Dimethoxy-4- 2C-E It can produce 2C-E binds to the 5- ethylphenethylamine C12H19NO2 strong synesthesia, sound HT2A receptor, distortion and visual causing its hallucinations. [42] intoxicating effects. Extremely long lasting, Duration of action 18–30 hours. 3,4-dimethyl-2,5- Discovered by Effects include hallucinations, dimethoxyphenethyla C H NO 2C-G Alexander Shulgin and increased appreciation of music, mine 12 19 2 described in his book powerful relaxation and

PIHKAL tranquillity.

2C-I Route: oral, snuffing, rectal, 2,5-dimethoxy-4- “smiles” [43] First synthesized parenteral Sparkling-white iodophenethylamine C10H14INO2 by Alexander Shulgin Effects include powder psychedelic or hallucinogenic ef

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fects. Adverse effects: muscle tension, nausea, vomiting, dilatation of pupil.

Quick onset of symptoms. Effects last up to 16 hours. 2,5-dimethoxy-4- 2CT2 First synthesized in Hallucinations, euphoria, ethylthiophenethylami 1981 by Alexander warm flushes , nausea, ne “rosy” Shulgin restlessness, neurotoxic.[44] Route: oral 5-HT2A receptor agonist in the brain Effects develop slowly and can 2,5-dimethoxy-4- Detected by tandem last 8–16 hours - isopropylthiophenethyl mass spectrometry 2 CT4 Hallucination , euphoria, amine C H NO S 13 21 2 anxiety. Risk of fatal adverse

events increase when it is taken along with or other drugs.[45]

Route: oral Effects last 8 to 15 hours 2C-T-7 has MAO-A Effects include sense of well- inhibitory effects. being ,increased appreciation 2-[2,5-Dimethoxy-4- 2C-T-7 It is more likely to of music, visual distortion, (propylthio)phenyl]eth Blue cause serotonin C H NO S , change in perception anamine 13 21 2 Mystic or 7t syndrome if of time, visual and auditory h Heaven administered along hallucinations, insomnia, with ephedrine or arrhythmia, paranoia, MDMA. nausea and vomiting, convulsions, tachycardia.[46]

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2-[2,5-Dimethoxy-4-(2- fluoroethylthio)phenyl]ethan Discovered by Effects include hallucinations, MAO inhibitor. 2C-T-21 amine Alexander Shulgin and high fever, tonic clonic It can lead to serotonin described in his book seizures, coma, death. syndrome. C12H18FNO2S PIHKAL 2-(8-bromo-2,3,6,7- tetrahydrofuro [2,3- 2CB-FLY f][1]benzofuran-4- First synthesized Effects include hallucinations, Unscheduled and

yl)ethanamine by Aaron P. Monte. deaths due to overdose. uncontrolled in USA

C12H14BrNO2 Slow onset of action. (6 hours after administration) Long duration of action lasting several days. It causes long-acting Off white powder. an 1-(4-Bromofuro[2,3- vasoconstriction leading extremely potent BROMODRAGONFL f][1]benzofuran-8- “fly” Bromo-DragonFly was to necrosis and gangrene. , only Y yl)propan-2-amine first synthesized by It can result in fatal slightly potent agonist Matthew Parker in 1998 overdosages, seizures, vomiting for 5-HT receptors C13NH12O2Br blood, and terrifying 2C and 5-HT receptors hallucinations. 2A Mislabelling bromodragonfly as other drugs which are less potent results in fatal overdosages.[47] 1-(4-Bromo-2,5- Slow onset of action than LSD dimethoxyphenyl)-2- Psychedelic effects like LSD. Sold as an alternative to DOB aminopropane high doses may cause LSD in the market serious vasoconstriction of the [48] C11H16BrNO2 extremities.

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Onset of the drug is 1–3 hours A selective 5-HT2A, 5- First synthesized by Ale Effects last for a day and HT2B, and 5- 1-(4-chloro-2,5-dimethoxy- xander Shulgin, and include increased awareness of HT2C receptor partial phenyl)propan-2-amine was described in his sound and agonist. Its DOC book PiHKAL (Pheneth movement,hallucinations, psychedelic effects are C11H16ClNO2 ylaminesi Have Known euphoria, nausea, vasoconstricti mediated via its And Loved) on, anion gap metabolic actions on the 5-HT2A acidosis with respiratory failure. receptor. Route: oral Duration of action 16 – 30 1-(2,5-dimethoxy-4- “trips” hours iodophenyl)- DOI was first The trip tends to be more DOI propan-2-amine synthesized energetic than an LSD trip. by Alexander Shulgin After effects include residual C H INO 11 16 2 stimulation, difficulty in sleeping.[49,50] Route: oral Duration of action : 8 hours Effects include perceptual changes such as blurred vision, DOM is a selective 5- 1-(2,5-Dimethoxy-4- It was first synthesized visual hallucinations, distorted STP - HT , 5-HT , and 5- methylphenyl)-2- by Alexander Shulgin, shapes, enhancement of details, 2A 2B Serenity, HT receptor partial DOM aminopropane and reported in his multiple images, vibration of 2C Tranquility, agonist. book PiHKAL: A objects, Peace C H NO Chemical Love Story slowed passage of time, 12 19 2 increased sexual drive and pleasure, pupillary dilation and a rise in systolic blood pressure. [51] 2-(4-chloro-2,5- Route: orally, NBOMe-2C-C, 25C- dimethoxyphenyl)-N-[(2- "Pandora" buccal, sublingual or NBOMe methoxyphenyl)methyl]etha insufflations.

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namine It produces hallucinations.[52]

C18H22ClNO3

25I-NBOMe is extremely potent Route: 25I-NBOMe is inactive orally.

The most common methods of

administration are sublingual, 2-(4-iodo-2,5- buccal or nasal dimethoxyphenyl)-N-[(2- Effects usually last 6-10 hours methoxyphenyl)methyl]etha Solaris, Discovered in 2003 and A

NBOMe-2C-I, 25I- namine N-Bomb, sold online as highly potent full agon Effects include euphoria, NBOMe Smiles, a designer drugs since ist for the human 5- alteration of perception, , C H INO 25I 2010 HT receptor. 18 22 3 aggression, visual and auditory 2A hallucinations, clonus, elevated

white cell count tachycardia , hypertension, agitation, seizures, hyperpyrexia, elevated creatine kinase, metabolic acidosis and acute kidney injury. [53] 4-methyl-2,5-dimethoxy-N- A potent agonist for [(2- the 5HT receptor. 2A NBOMe-2C-D, 25D- methoxyphenyl)methyl]benz Divination It produces similar effects in

NBOMe eneethanamine humans to related compounds

such as NBOMe-2C-I [54] C19H25NO3 and NBOMe-2C-C.

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Table 7: Designer Drugs-Psychedelics ( Based) Pharmacokinetics Iupac Name Discovery And Designer Drug Street Name Pharmacodynamic and Adverse Remarks Chemical structure Historical Aspects Effects 3-[2-[bis(1- Route: oral 4-Acetoxy-DiPT Described in methylethyl)amino]ethyl]-1H- Onset of action 20–60 minutes TIHKAL Off-white Indol-4-ol acetate Ipracetin Effects last 1–4 hours and include (4-acetoxy-N, ( I Have powder open and closed-eye visual N- ) Loved And Known) [55] C18H26N2O2 hallucinations It is an Route: oral analog of Effects last 4-6 hrs. . The onset of action is described as Psilocin is smooth, gentle and pleasant. a Schedule Effects include enhanced visual I drug under Psilacetin, 4- perception, mental and physical the Controlled 3-[2-(Dimethylamino)ethyl]- Patented on January O-Acetylpsilocin Acetoxy-DMT, stimulation, euphoria, increased Substances 1H-indol-4-yl acetate 16, 1963 4-AcO-DMT laughing, sexual arousal. Act of by Sandoz Ltd It can also cause mydriasis, the USA. C H N O 14 18 2 2 confusion, alterations in time and O- colour perception, synesthesia, Acetylpsilocin sedation, auditory and visual is illegal in distortions, anxiety, insomnia, the UK under paranoia, motor impairment, the Misuse of vertigo, confusion, tachycardia.[56] Drugs Act 1971. 3-(2- Route: oral 4-HO-MET 4-HO-MET was first (ethyl(methyl)amino)ethyl)- Duration of action 4 - 6 hrs 4-hydroxy-N-methyl-N- Metocin synthesized 1H-indol-4-ol Effects include euphoria, changes ethyltryptamine by Alexander Shulgin [57] C13H18N2O in thought processes. 4-HO-MiPT 3-(2- Miprocin First synthesized by Route: oral Partial

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[Isopropyl(methyl)amino]ethyl Alexander Shulgin Duration of action 4 - 6 hrs agonism of 5- 4-Hydroxy-N-methyl-N- )-1H-indol-4-ol and described in his Effects include euphoria, auditory HT2A and 5- isopropyltryptamine book TIHKAL and visual hallucinations. HT1A

C14H20N2O Adverse effects include motor receptors incoordination, mild vertigo[58]

Route: oral, intravenous and intramuscular 5-MeO-Amt 1-(5-methoxy-1H-indol-3- Effects include euphoria, visual and yl)propan-2-amine auditory hallucinations, increased Alpha-O 5-methoxy-α- energy and awareness methyltryptamine C12H16N2O Adverse effects include headache, fever, nausea, vomiting, insomnia, paranoia, aggressive behaviour, cardiac arrhythmia and seizures. [59] Route: oral, inhaled, injected Effects include auditory and visual 3-[2- distortions, hallucinations, sexual (Diisopropylamino)ethyl]-5- 5-Methoxy- enhancement, improved self methoxyindole diisopropyltryptamine Foxy, confidence, diminished fear and

Methoxy anxiety C H N O -MeODiPT 17 26 2 Side effects include nausea,

vomiting, hypotension, mydriasis,

tachycardia, rhabdomyolysis and renal failure. [60] 5-MeO-MiPT the N-methyl-N- Route: oral, smoking isopropyl homologue of the It has a very strong odour. Moxy 5-methoxy-N-methyl-N- psychedelic, 5-MeO-DMT Effects include synesthesia, isopropyltryptamine tachycardia, vasoconstriction[61] Diisopropyltryptamine, N,N- Route: oral Diisopropyltryptamine diisopropyltryptamine, 3-[2- DiPT Duration of action 6 - 8 hrs

(diisopropylamino)ethyl]indole Effects include auditory

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hallucination, confusion, [62] C16H24N2 imbalance, lack of coordination Route: oral, intravenous or intramuscular injection 3-[2- Angel of the Duration of action 2 - 4 hrs (dipropylamino)ethyl]indole Host Effects include increased intensity C H N 16 24 2 of music, visual and auditory hallucinations, synaesthesia [63]

Dissociatives - Dissociatives are a class of hallucinogen, which distort perceptions of sight and sound and produce sensory deprivation and feelings of detachment and dissociation from the environment and self. They are the variants of the anaesthetic agent and the drug of abuse, Phencyclidine. Overdoses can cause respiratory depression, coma and even death. (Table 8).

Table 8: Designer Drugs - Dissociatives DESIGNER DRUG IUPAC NAME COMMON DISCOVERY PHARMACOKINETICS REMARKS CHEMICAL NAME AND PHARMACODYNAMIC STRUCTURE HISTORICAL AND ADVERSE EFFECTS ASPECTS 3-Methoxyphencyclidine (3- 1-[1-(3- 3-MeO-PCP First appeared Duration lasts: 7-8 hours. reuptake MeO-PCP) methoxyphenyl)cycloh around 2009 Oral anaesthetic drug inhibitor and NMDA exyl]-piperidine with hallucinogenic and sedati antagonist with same C18H27NO ve effects potency as phencyclidine 4- 1-[1-(4- 4-MeO-PCP First sold in the anaesthetic drug Methoxyphencyclidine (metho methoxyphenyl)cycloh UK in 2008 as with hallucinogenic and sedati xydine, 4-MeO-PCP) exyl]-piperidine a designer ve effects[64] drug and researc C18H27NO h chemical by a company trading under the name

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CBAY [5R,10S]-[+]-5-methyl- MK-801 Discovered by a Active dose in the 50-100 μg Antagonist at 10,11- dihydro-5H- team at Merck in range. the NMDA receptor dibenzo[a,d]cyclohepte 1982 Strong auditory and nicotinic n-5,10-imine hallucinations, amnesia and acetylcholine receptor residual deficits in thinking[65] . It inhibits the C16H15N serotonin and dopamine transporters N-ethyl-1- PCE, CI-400 Developed by Dissociative anaesthetic drug phenylcyclohexylamine Parke-Davis in with hallucinogenic effects the 1970s

C14H21N (MXE) or 3- (RS)2-(3- First identified in White powder NMDA receptor MeO-2-Oxo-PCE methoxyphenyl)-2- Mexxy November 2010 half life- 3 to 6 hours antagonist and seroton (ethylamino)cyclohexa in reuptake none inhibitor[67] Dissociative drug that causes

C15H21NO2 hallucinations and can lead to acute cerebellar toxicity[66] PCPr N-(1- Sold as Dissociative anaesthetic drug phenylcyclohexyl)prop a designer with hallucinogenic and sedati anamine drug in Germany ve effects[68] and other C15H23N European countries since the late 1990s 1-(1- PcPY Similar in effects to phenylcyclohexyl)pyrro phencyclidine. lidine It is slightly less potent ; it acts by inducing a C16H23N effect with additional PCP-

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like dissociative and hallucinogenic effects[69]

Tenocyclidine 1-(1-(2- A dissociative anaesthetic dru Non-competitive Thienyl)cyclohexyl)pip g similar in effects antagonist at the 3A- eridine to phencyclidine (PCP) but is subunit of the NMDA

C15H23NS considerably more potent. receptor.

N-Ethylnorketamine 2-(2-Chlorophenyl)-2- NEK Sold over the Similar properties (ethylamino)cyclohexa internet since to ketamine n-1-one late 2012

C14H18ClNO

Methoxyketamine 2-(2-Methoxyphenyl)- 2-MeO-2- First reported in Functions as an NMDA 2- deschloroketa 1963 . (methylamino)cyclohex mine Produces sedative, anone hallucinogenic, and anaesthetic effects C14H19NO2

Piperazine-based designer drugs - These are chemical compounds which contain a core piperazine functional group. These are extremely common adulterants in clubs, often being sold as MDMA-Methylene dioxy methamphetamine. (Table 9)

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Table 9: Designer Drugs- Piperazine Based DESIGN IUPAC NAME DISCOVERY AND PHARMACOKINETICS ER CHEMICAL STREET NAME HISTORICAL PHARMACODYNAMIC AND REMARKS DRUG STRUCTURE ASPECTS ADVERSE EFFECTS Route: oral, IV, insufflations

Hepatic metabolism, Half life (t ½) is 5.5 hours, Renal excretion.[70] Effects include feelings of euphoria, increased energy, enhanced appreciation of music, skin tingling, decreased appetite, It acts on Originally repetitive thought patterns the and 1- Pepper extract, synthesized as a dopaminergic recepto Benzylpip Herbal high, potential anti- Adverse effects include acute rs.It is an antagonist erazine C H N Jet 11 16 2 parasitic agent. Used psychosis,blurred vision, dry mouth, at the 2

recreationally since pruritus, confusion, agitation, tremor, receptor causing an

the early 1990s extrapyramidal symptoms increase in release (dystonia, akathisia), headache, dizziness, of noradrenaline anxiety, insomnia, vomiting, Increased heart rate, dilation of pupils ,flushing , hallucinations, paresthesia, tachycardia, hyp ertension, palpitations, collapse, hyperventilation, sweating, hyperthermia, renal toxicity, respiratory failure, hyperthermia, serotonin syndrome, rhabdomyolysis and seizure.[71]

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Routes- oral, nasal, rectal m-CPPP 1-(3- It undergoes hepatic metabolism and renal mCPP is metabolized meta- chlorophenyl)piperaz It was initially excretion, via the CYP2D6. Chlorophe ine developed in the late- half life is 2-6 hrs It has affinity for α- nyl 1970s and was sold adrenergic receptors. piperazine C10H13ClN2 as a designer drug in Psychedelic effects are caused by It behaves as the mid-2000s 5-HT2A activation while negative effects such an agonist at most as anxiety, headache and appetite loss are serotonin receptors[72] likely mediated by its actions on the 5- HT2C receptor para- 1-(4- Inhibit the reuptake a Party pills Methoxyp methoxyphenyl)piper Oral route doses between 120–200 mg. nd induce MeOPP, henyl azine It undergoes hepatic metabolism and renal the release of pMPP, piperazine excretion the monoamine neuro Paraperazine C11H16N2O transmitters Route: oral route It undergoes hepatic metabolism and renal pFPP, 4- 1-(4- excretion FPP; Fluoperazine, para- fluorophenyl)piperaz t ½ is 6-8 hrs Flipiperazine Fluorophe ine Serotonin and nor nyl The stimulant effects are lesser than other adrenaline reuptake Party pills, piperazine C H FN drugs in the group. inhibitor. 10 13 2 The Big Grin, Side-effects include migraine, muscle Mashed, and aches, anxiety, nausea, and vomiting. pFPP is Extreme Beans[73] an inhibitor of cytochrome P450 enzymes in the liver Trifluoro 1-[3- Route: oral methyl (trifluoromethyl)phe Side effects including migraine, headaches, phenylpip nyl]piperazine Legal X[74] muscle aches, nausea, erazine vomiting, insomnia, loss of appetite,

C11H13F3N2 and headache

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Table 10: Designer Drugs-Stimulants IUPAC NAME DISCOVERY AND PHARMACOKINETICS STREET DESIGNER DRUG CHEMICAL HISTORICAL PHARMACODYNAMIC AND REMARKS NAME STRUCTURE ASPECTS ADVERSE EFFECTS

Alpha- (RS)-1-Phenyl-2-(1- Detected by laboratories Pyrrolidinopropiophen pyrrolidinyl)-1- in Germany as an α-PPP Stimulant drug one propanone ingredient in "ecstasy"

C13H17NO tablets. (RS)-1-(3- Stimulant drug which acts as a 3-Fluoroamphetamine fluorophenyl)propan- 3-FA monoamine releaser.

2-amine PAL-353 It has similar potency

C9H12FN to methamphetamine Route: oral Effects start within an hour after ingestion and last 4–10 hours. (RS)-1-(4-

Fluorophenyl)propan- 4-Fluoroamphetamine Flux, Flits, Effects include euphoria similar to the 2-amine R2D2, Miley effects of MDMA, mood elevation,

excessive talking, increased energy and C H FN 9 12 anorexia. Side effects are nausea, headaches, increased heart rate and insomnia[75] Route: oral, vaporized, insufflated, injected

4-Methyl-5-phenyl-2- Euphoria and First synthesized in It undergoes hepatic metabolism and 4-Methylaminorex amino-oxazoline Ice 1960 by McNeil renal excretion. (4-MAR, 4- Laboratories. C H N O MAX 10 12 2 Effects are stimulant in nature, producing euphoria, increased attention and cognition. It can also cause

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pulmonary hypertension Route: oral, rectal, vaporization, insufflation, intravenous, intramuscular α-methylamino- 2-(methylamino)-1- Effects include euphoria , elevated butyrophenone phenylbutan-1-one mood, increased alertness, increased (MABP) C H NO 11 15 heart rate, increased sexual drive, insomnia, sweating N-methyl-2- (N- phenylbicyclo[2.2.1]he Designer drug following methyl-3-phenyl- ptan-3-amine Camfetamine the banning Stimulant drug norbornan-2-amine) of C14H19N (RS)-2- Route: oral, nasal, sublingual benzhydrylpiperidine 2- Developed in the 1950s 90% bioavailability diphenylmethyl for the treatment It undergoes hepatic metabolism C18H21N piperidine (2- of narcolepsy and It is a stimulant drug which acts as DPMP) ADHD norepinephrine-dopamine (NDRI) Relatively diphenyl(pyrrolidin-2- Stimulant drug. mild norepinep (D2 yl)methanol Head Candy Adverse effect include cardiovascular hrine-dopamine PM) toxicity reuptake C H NO 17 19 inhibitor Route : insufflation, vaporized, Potent psychos intravenous, intramuscular, rectal, oral, timulant (RS)-ethyl 2-phenyl-2- sublingual drug that acts piperidin-2-ylacetate It undergoes hepatic metabolism and as both renal excretion. dopamine C H NO 15 21 2 The half life is 4 hours reuptake inhibitor and n

Insufflation can result in a perforated orepinephrine septum reuptake

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inhibitor

(RS)-1-(4- fluorophenyl)-2- Stimulant drug which leads to euphoria 4-fluoro started to be methylaminopropan-1- Adverse effects include Flephedrone ( sold as a designer - one hyperthermia, convulsions, neurotoxicit 4-FMC) drug in 2008 y[76]

C10H12FNO

It is a Route: norepinephrine oral, insufflation, smoking, rectal -dopamine and intravenous. reuptake Effects last for 4-6 hours. inhibitor (NDR (RS)-1- MDPV is metabolised by CYP I). (Benzo[d][1,3]dioxol- enzymes. Quantitated in Methylenedioxypyrov 5-yl)-2-(pyrrolidin-1- First developed Effects include euphoria, increased blood and urine alerone (MDPV) yl)pentan-1-one in the 1960s alertness, energy, wakefulness and by gas awareness, sexual stimulation, chromatograph [77] C16H21NO3 anorexia y-mass spectrometry or It can cause panic attacks, psychosis, liquid hypertension, tachycardia, and seizures chromatograph y-mass spectrometry (RS)-2-methylamino- Quantitated in 1-(4- Drone, Mephedrone causes euphoria, blood, plasma methylphenyl)propan- MCAT, First synthesised in 1929 decreased hostility, stimulation, an or urine by gas Mephedrone 1-one Bubbles, Rediscovered in 2003 enhanced appreciation for music, chromatograph 4-MMC elevated mood, ,improved mental y-mass

C11H15NO function and mild sexual stimulation. spectrometry to

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confirm a Adverse effects include dilated pupils, diagnosis. poor concentration, bruxism, poor short-term memory, hallucinations, delusions, and erratic behaviour., breathing difficulties, loss of appetite, increased sweating, changes in body temperature, increased heart rate, hallucinations, agitation, excitability and mania, anxiety, paranoia and depression . Insufflation can lead to nose bleeds.[78] (RS)-1-(4- Effects produced are similar to Para- methoxyphenyl)-2- both MDMA and which include methoxymethca (methylamino)propan- increased sociability, energy, euphoria, thinone, 1-one disinhibition and stimulation. Methedrone bk- Adverse effects include pupil PMMA, PMM C H NO dilation, hyperthermia, increased 11 15 2 C, methoxyphe perspiration, severe hyperthermia and drine even death 1-(thiophen-2-yl)-2- methylaminopropane Originally appeared for public sale in the UK in Blow Stimulant drug C8H13NS December 2010 as a "research chemical"

(RS)-1-naphthalen-2- NRG-1 It is a triple yl-2-pyrrolidin-1- emerged reuptake Naphyrone ylpentan-1-one O-2482, Legal months after the ban of Stimulant drug inhibitor high, drug mephedrone affecting C19H23NO Naphthylpyrov the reuptake of

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alerone the neurotrans mitters serotoni n, dopamine an d norepinephrin e (±)-1-phenyl-2- (methylamino)pentan- 1-one Bath salt sold Stimulant drug as legal highs C12H17NO

(±)-1-(1,3- benzodioxol-5-yl)-2- (methylamino)pentan- Novel designer 1-one drug,

bk-MBDP

C13H17NO3 NRG-1

(RS)-1-(4- fluorophenyl)-2- Flephedrone started to be methylaminopropan-1- Overdose can lead to hyperthermia Flephedrone 4-FMC sold as a designer one and convulsions drug in 2008

C10H12FNO Stimulants – These are synthetic drugs that induce temporary improvements in either mental or physical functions or both. They are derivatives of amphetamine type stimulants . They lead to enhanced alertness and wakefulness and can produce physical as well as psychological dependence.( Table 10)

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5. IMPLICATIONS The manufacture, availability and use of designer drugs has resulted in amplifying the already existing problem related to drug abuse. The problems may be categorized as

MEDICAL While there is lack of documented scientific data about the medical effects of the newly developed designer drugs, the medical implications of designer drugs can be many and profound. Designer drugs are marketed with innocuous names such as „legal highs‟, „club drugs‟, „spice‟, „ bath salts‟, „potpourri‟ , „meow‟ and hence mislead the youngsters into believing that they are indulging in low risk substances. Since no proper guidelines and techniques are involved in the synthesis of these new compounds, their effects on the human body are largely unpredictable. In the absence of quality control, the dose of these drugs cannot be ascertained and hence leads to frequent overdoses and harmful effects. For instance, the overdose of synthetic opioids can cause respiratory depression while the overdose of can lead to coma and death.

Social The social implications for the designer drugs are expected to be the same as that of the known drugs of abuse. While there is very little documented data on the effects of designer drugs on the society, drug abuse which includes synthetic drugs can adversely affect the whole society. Drug addicts cannot offer a stable family life to their children. Many of these children run away from homes living on the streets and the probability of them becoming addicts in turn is quite high. Drugs like MDMA and PCP have been seen to increase the likelihood of domestic violence. Designer drug use can lead to increased aggressiveness, sexual abuse, putting individuals at risk to contract HIV and other sexually transmitted diseases.

Links between trade of illicit drugs, crime syndicates and terrorist organisations has been established. The enormous money associated with the trade of designer drugs is channelized in the promotion of terrorism and other antisocial activities. Addicted parents often get indebted, steal from friends or family or lose their job. “Rave parties” which involve the use of new designer drugs are gaining popularity among the youth. After increasing crackdown on the use of illegal drugs in nightclubs, these parties have moved into residential neighbourhoods where finding the evidence to perform a raid is more difficult to acquire. Many young professionals in India are moving towards drug use because of stress, peer www.wjpps.com Vol 4, Issue 08, 2015. 327 Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences

pressure and rise in incomes. Drug traffickers are quite willing to take advantage of this emerging market by introducing new psychoactive substances or designer drugs.79

Economic: The exact data of the economic impact of designer drugs is not available. However, it is estimated that trafficking in illicit drugs is the largest illegal business in the world, making about 8% of the international trade (about $400 billion annually).80 A major portion of this illicit drug trade comprises of designer drugs. The exponentially increasing demand coupled with inability of law enforcing agencies to curb the development of designer drugs, encourages the trade of “research chemicals” leading to the synthesis of newer designer drugs. The enormous profits involved in trade of designer drugs lures many individuals especially in the developing countries to engage in the manufacture and trafficking of such drugs.

Legal: Many laws in different countries have been made to prohibit the manufacture, trade and use of illicit drugs including designer drugs. However, not all drugs of abuse are controlled under such laws because new designer drugs are synthesized from the banned drugs in order to circumvent the ban. The enforcement of laws and the discovery of newer drugs to evade these laws has been a continuous process. It has been difficult for the law enforcing agencies to keep up with the pace of development of new illicit drugs or designer versions of older drugs.

United States of America: Under the Federal Law, The Controlled Substances Act (CSA) prohibits unauthorized manufacturing, distributing, or dispensing of controlled substances. It also prohibits their possession for the purpose of distributing or dispensing.[81] United Kingdom: The Misuse of Drugs Act 1971 prevents the trafficking of illegal drugs in the United Kingdom.

India: In India, the cultivation, production, manufacture, possession of illicit drugs is regulated by a special act, Narcotic Drugs and Psychotropic Substances Act,1985.

The Act states -The cultivation, production, manufacture, possession, sale, purchase, transportation, warehousing, consumption, inter-State movement, transshipment and import and export of narcotic drugs and psychotropic substances is prohibited, except for medical or scientific purposes and in accordance with the terms and conditions of any license, permit or authorization given by the Government.[82]

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6. DETECTION AND ANALYSIS Since these drugs are developed by modifying chemical structures of banned drugs, it is difficult to detect these drugs using existing methods for drug analysis. Methods commonly used for drugs of abuse include colorimetric detections, gas chromatographic (GC)–mass spectrometric, and liquid chromatographic (LC)–mass spectrometric.[83] However, newer drugs are constantly developed in order to evade the current detection techniques. It is necessary to predict the modifications possible in the existing drugs and develop techniques to detect such modified compounds and potential new psychoactive substances.

Since the 1990s, the internet has become the main source of obtaining information regarding manufacture and sale of designer drugs. Eighty eight per cent of countries responding to a United Nations Organisation for Drug Control (UNODC) survey said that the Internet served as a key source for the supply in their markets. The designer drugs developed in various clandestine laboratories are sold in the market through internet based pharmacies.[84]

7. CONCLUSION Designer drugs have come to play an increasing role as drugs of abuse. The fact that they are modifications of existing controlled drugs makes their detection difficult. Although the exact data about these drugs is not available, it is important to control the development and trade of these new drugs of abuse since they are proving to be an emerging health hazard. Society at large, health personnel and the law enforcing agencies should be aware of rise in use of designer drugs and its consequences.

REFERENCES 1. The challenge of new psychoactive substances [Internet]. United Nations Office on Drugs and Crime report 2013[cited 2015 Jan 20]. Available from: http://www.unodc.org/documents/scientific/NPS_2013_SMART.pdf. 2. The International Narcotics Control Board [Internet] 2010 [ cited 2015 Jan 20]. Available from: http://www.incb.org/documents/Publications/AnnualReports/AR2010/AR_2010_forewor d.pdf. 3. European Monitoring Centre for Drugs and Drug Addiction ,Europol. New drugs in Europe, 2012; Annual Report on the implementation of Council Decision 2005/387/JHA. Luxembourg. EMCDDA-Europol; 2013.

www.wjpps.com Vol 4, Issue 08, 2015. 329 Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences

4. Designer Drugs History [Internet]. [cited 2015 Jan 21] Available from: http://www.erowid.org/archive/rhodium/chemistry/designer.drugs.history.html. 5. Heroin and the International Conferences on Narcotics of 1925 and 1931 [Internet] [cited 2015 Jan 21] Available from: http://www.unodc.org/unodc/en/data-and- analysis/bulletin/bulletin_1953-01-01_2_page013.html. 6. Lsd: A Short History [Internet].[cited 2015 Jan 22] Available from:http://www.drugfreeworld.org/drugfacts/Lsd/A-Short-History.html 7. Henderson G. L. Designer Drugs: Past History and Future Prospects. J. Forensic Sci. 1988; 33(2): 569-75. 8. 2013 World Drug Report Finds Increase in Synthetic and Designer Drug Use [Internet] CADCA; 2013 Jun 27 [cited 2015 Jan 23] Available from: http://www.cadca.org/resources/detail/2013-world-drug-report-finds-increase-synthetic- and-designer-drug-use. 9. UNODC. World Drug Report 2012. [Internet] Vienna. United Nations Office on Drugs and Crime. Jun 2012[cited 2015 Jan 24] Available from: http://www.unodc.org/documents/data-and- analysis/WDR2012/WDR_2012_web_small.pdf. 10. World Drug Report 2011[Internet]. http://www.unodc.org/documents/data-and- analysis/WDR2012/WDR_2012_web_small.pdf…..World Drug Report 2011 11. International Narcotics Control Board. Report of the International Narcotics Control Board for 2012. New York. United Nations. Jan 2013. Available from: http://incb.org/documents/Publications/AnnualReports/AR2012/AR_2012_E.pdf. 12. India a hub of designer drugs: INCB. [Internet] GN Bureau; 2011 Mar 3[cited 2015 Jan 24] Available from: http://www.governancenow.com/views/think-tanks/india-hub- designer-drugs-incb. 13. International Narcotics Control Board. Report of the International Narcotics Control Board for 2012 . New York. United Nations. Jan 2013. Available from: http://incb.org/documents/Publications/AnnualReports/AR2012/AR_2012_E.pdf 14. UNODC. World Drug Report 2012. [Internet] Vienna. United Nations Office on Drugs and Crime. Jun 2012[cited 2015 Jan 27] Available from: http://www.unodc.org/documents/data-and- analysis/WDR2012/WDR_2012_web_small.pdf. 15. Opiates(Narcotics): Addiction, Withdrawal and Recovery[Internet][cited 2015 Jan 30] Available from: http://www.addictionsandrecovery.org/opiates-narcotics-recovery.htm www.wjpps.com Vol 4, Issue 08, 2015. 330 Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences

16. Kram TC, Cooper DA, Allen AC. Behind the identification of China White. .1981; 53 (12): 1379–86. 17. Alpha methylfentanyl; Martindale- The Extra Pharmacopoeia, 30th ed p1078. 18. Moscow theatre hostage crisis remembered [Internet]. 2010 Oct 26[cited 2015 Feb 10] ; Available from: http://www.demotix.com/news/486772/moscow-theatre-hostage-crisis- remembered-moscow#media-486767. 19. Ojanperä I, Gergov M, Liiv M, Riikoja A, Vuori E. An epidemic of fatal 3- methylfentanyl poisoning in Estonia. Int J Legal Med. 2008 Sep;122(5):395-400. 20. Street-Drug Contaminant causing Parkinsonism .CDC MMWR.[Internet]. 1984 June 22[cited 2015 Feb 10] Available from: http://www.cdc.gov/mmwr/preview/mmwrhtml/00000360.htm. 21. Sian J et al. MPTP-Induced Parkinsonian Syndrome. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. [Internet]Philadelphia: Lippincott-Raven; 1999.[cited 2015 Feb 5] Available from: http://www.ncbi.nlm.nih.gov/books/NBK27974/ 22. Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional Fatal Intoxications with Mitragynine and O-Desmethyltramadol from the Herbal Blend Krypton [Internet]..Journal of Analytical Toxicology, Vol.35, 2011 May. Available from: http://jat.oxfordjournals.org/content/35/4/242.full.pdf. 23. Caspi H.Drug Expert Explains Facts on Krokodil. EMSWorld.[Internet]. 2013 Oct 14[cited 2015 Feb 24]. Available from: http://www.emsworld.com/article/11191331/drug-expert-explains-facts-on-krokodil- desomorphine-flesh-skin-rotting-drug. 24. “Krokodil”. New York State Office Of Alcoholism And Substance Abuse Services.[Internet] 2012 Feb[cited 2015 Feb 24]. Available from: ttp://www.oasas.ny.gov/admed/fyi/krokodil.cfm 25. AM-1220[Internet] 2013 Jan 26[cited 2014 Mar 1] Available from: http://www.drsynthetic.com/t/am-1220-cannabinoid/ . 26. AM-2201.Drugs-Forum.[Internet] [cited 2015 Mar 1] Available from: http://www.drugs- forum.com/forum/showwiki.php?title=AM-2201. 27. ekaJ. “The Night I Killed My Friends: An Experience with AM-2201(ID 89294)” [Internet] 2011 Feb 20[cited 2015 Mar 1]. Available from: http://www.erowid.org/experiences/exp.php?ID=89294. 28. JWH-007. Drugs-Forum.[Internet] [cited 2015 Mar] Available from: http://www.drugs- forum.com/forum/showthread.php?t=105345#ixzz2thCM5UJ6. www.wjpps.com Vol 4, Issue 08, 2015. 331 Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences

29. Shanks K, Dahn T,Terrell A..Detection of JWH-018 and JWH-073 by UPLC–MS-MS in Postmortem Whole Blood Casework. J Anal Toxicol (2012) 36 (3): 145-52.[Internet] 2012 [cited 2015 Mar 3] Available from: http://jat.oxfordjournals.org/content/36/3/145.long. 30. Brock D. The Metabolism of JWH-type Synthetic Cannabinoids.Cayman chemical [Internet] [cited 2015 Mar 1] Available from: https://www.caymanchem.com/app/template/Article.vm/article/2198. 31. [JWH-073] Body high with rush. The Trip Report. [Internet] 2011 Jan 20 [cited 2015 Mar 1] Available from: http://the-tripreport.com/site/tripreport/jwh-073/. 32. MasXtreme contains Aildenafil and [Internet] UKmedix online pharmacy; 2010 Apr 5 [cited 2015 Mar 3] Available from: http://www.ukmedix.com/news/viagra/masxtreme_contains_aildenafil_and_phentolamine 5355.cfm. 33. Acetildenafil. [Internet] Cayman chemical [cited 2015 Feb 20] Available from: https://www.caymanchem.com/app/template/Product.vm/catalog/12049/promo/emolecule s. 34. Aziffa Side Effects: Sulfoaildenafil is Dangerous to Your Health. [Internet] Sex Drugs. 2012 Jul 9[cited 2015 Feb 24] Available from: http://healthsideeffects.org/aziffa-side-effects.html 35. “ViaXtreme” Contains Undeclared Drug Ingredient.[Internet] US Food and Drug Administration; [Internet] 2011 May 29 [ cited 2015 Feb 23] Available from: http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/M edicationHealthFraud/ucm257161.htm. 36. Pereira HM, Padilha MC, Neto FR. Tetrahydrogestrinone analysis and designer steroids revisited. Bioanalysis. 2009 Nov;1(8):1475-89 . [cited 2015 Mar 1] Available from: http://www.ncbi.nlm.nih.gov/pubmed/21083096. 37. Groot A, Koert W. Designer Steroids.Het Anabolenboek.[Internet]. 2007 Sep 15[cited 2015 Feb 25]; Available from: http://www.ergogenics.org/anabolenboek/index18en.html 38. How to use Superdrol safely. The Anabolic Insider [Internet]. 2012 May 7[cited 2015 Feb 25]; Available from: http://theanabolicinsider.com/superdrol-safetly/. 39. Desoxymethyltestosterone.FindTheBest [Internet] [ cited 2015 Feb 25 ] Available from: http://controlled-substances.findthebest.com/l/267/Desoxymethyltestosterone. 40. Shulgin A. ETH-LAD.PiHKAL[Internet] [ cited 2015 Mar 22] Available from: https://www.erowid.org/library/books_online/tihkal/tihkal12.shtml.

www.wjpps.com Vol 4, Issue 08, 2015. 332 Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences

41. Shulin A. 2C-C. PiHKAL. [Internet] [cited 2015 Mar 23] Available from: https://www.erowid.org/library/books_online/pihkal/pihkal022.shtml. 42. Shulin A. 2C-E. PiHKAL. [Internet] [cited 2015 Mar 25] Available from: http://www.erowid.org/library/books_online/pihkal/pihkal024.shtml. 43. Weiss P,Staff S. 2C-I or 'Smiles': The New Killer Drug Every Parent Should Know About. [Internet] 2013 Sep 20[cited 2015 Mar] Available from: http://greggornation.com/2012/10/02/2c-i-or-smiles-the-new-killer-drug-every-parent- should-know-about/. 44. Shulin A. 2C-T-2. PiHKAL. [Internet] [cited 2015 Mar 23] Available from: https://www.erowid.org/library/books_online/pihkal/pihkal022.shtml. 45. Kerrigan S, Mott A, Jatzlau B, Ortiz F, Perrella L, Martin S, Bryand K. Designer psychostimulants in urine by liquid chromatography-tandem mass spectrometry. J Forensic Sci. 2014 Jan; 59(1): 175-83. 46. Murple. 2C-T-2 Sulfurous Samadhi.The Vaults of Erowid. [Internet] 2001 Feb 6 [cited 2015 Mar 27] Available from: https://www.erowid.org/chemicals/2ct7/article1/chemistry.shtml. 47. Bromo-Dragonfly. Drugs-Forum. [Internet] [cited 2015 Mar 28] Available from: http://www.drugs-forum.com/forum/showwiki.php?title=Bromo-Dragonfly. 48. Shulgin A. DOB. PiHKAL. [Internet] [cited 2015 Mar 28] Available from: http://www.erowid.org/library/books_online/pihkal/pihkal062.shtml. 49. DOI. Drugs-Forum. [Internet] [cited 2015 Mar 29] Available from: http://www.drugs- forum.com/forum/showthread.php?t=11713. 50. Shulgin A. DOI. PiHKAL.[Internet] [cited 2015 Mar 29] Available from: https://www.erowid.org/library/books_online/pihkal/pihkal067.shtml. 51. DOM.Drugs-Forum. [Internet] [cited 2015 Mar 30] Available from:http://www.drugs- forum.com/forum/showthread.php?t=42378. 52. 25C-NBOMe-2C-C. Drugs-Forum. [Internet] [cited 2015 Mar 30] Available from:http://www.drugs-forum.com/forum/showthread.php?t=146400. 53. Erowid. 25I-NBOMe. The Vaults of Erowid. [Internet] [cited 2015 Mar 30] Available from: https://www.erowid.org/chemicals/2ci_nbome/2ci_nbome_effects.shtml. 54. Psyke. 25D-NBOMelated.Erowid Experience Vaults. [Internet] 2011 Jun 11[cited 2015 Mar 30] Available from: http://www.erowid.org/experiences/exp.php?ID=91460. 55. Shulgin A.4-HO-DIPT ;TiHKAL [Internet] [cited 2015 Apr 2] Available from: https://www.erowid.org/library/books_online/tihkal/tihkal17.shtml. www.wjpps.com Vol 4, Issue 08, 2015. 333 Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences

56. 4-Acetoxy-DMT ;The Vaults of Erowid [Internet] [cited 2015 Apr 2] Available from: http://www.erowid.org/chemicals/4_acetoxy_dmt/4_acetoxy_dmt_effects.shtml. 57. Shulgin A. 4-HO-MET;TiHKAL[Internet] [cited 2015 Apr 3] Available from: https://www.erowid.org/library/books_online/tihkal/tihkal21.shtml. 58. Shulgin A.4-HO-MIPT ;TiHKAL [Internet] [cited 2015 Apr 3] Available from: http://www.erowid.org/library/books_online/tihkal/tihkal22.shtml. 59. Shulgin A. a,O-DMS ;TiHKAL [Internet] [cited 2015 Apr 4] Available from: https://www.erowid.org/library/books_online/tihkal/tihkal05.shtml. 60. 5-MeO-DIPT;The Vaults of Erowid [Internet] [cited 2015 Apr 4] Available from: http://www.erowid.org/chemicals/5meo_dipt/5meo_dipt_effects.shtml. 61. Shulgin A.5-MEO-MIPT ;TiHKAL [Internet] [cited 2015 Apr 5] Available from: http://www.erowid.org/library/books_online/tihkal/tihkal40.shtml. 62. Shulgin A. DIPT ;TiHKAL [Internet] [cited 2015 Apr 5] Available from: http://www.erowid.org/library/books_online/tihkal/tihkal04.shtml. 63. hulgin A. DPT ;TiHKAL [Internet] [cited 2015 Apr 5] Available from: http://www.erowid.org/library/books_online/tihkal/tihkal09.shtml. 64. Erowid.4-Meo-PCP. The Vaults Of Erowid [Internet] cited 2014 Mar 16; Available from: http://www.erowid.org/chemicals/4meo_pcp/4meo_pcp_effects.shtml. 65. Kovacic P,Somanathan R. Electron transfer, radicals, redox metabolites and bioactivity . Oxid Med Cell Longev. 2010 Jan; 3(1): 13–22. 66. EMCDDA–EuropolJoint Report on a new psychoactive substance: methoxetamine (2-(3- methoxyphenyl)-2-(ethylamino)cyclohexanone. [Internet] [cited 2015 Mar 17] Available from: http://www.emcdda.europa.eu/publications/joint-report/methoxetamine. 67. Kjellgren, Jonsson K. Methoxetamine (MXE) – A Phenomenological Study of Experiences Induced by a “Legal High” from the Internet..J Psychoactive Drugs. 2013 July; 45(3): 276–86. 68. Sauer C, Peters FT, Staack RF, Fritschi G, Maurer HH. Metabolism and toxicological detection of a new designer drug, N-(1-phenylcyclohexyl)propanamine, in rat urine using gas chromatography-mass spectrometry. J Chromatogr A. 2008 Apr 4;1186(1):380-90 69. Rolicyclidine ;DrugBank; cited 2013 January[Internet] [cited 2015 April 7] Available from: http://www.drugbank.ca/drugs/DB01549. 70. Schep LJ, Slaughter RJ, Vale JA, Beasley DM. The clinical toxicology of the designer "party pills" benzylpiperazine and trifluoromethylphenylpiperazine. PClinToxicol (Phila). 2011 Mar; 49(3): 131-41. www.wjpps.com Vol 4, Issue 08, 2015. 334 Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences

71. PMA. Drugs.ie.[Internet] [cited 2015 Apr 18] Available from: http://www.drugs.ie/drugtypes/drug/benzylpiperazine A recreational drug with euphoriant and stimulant properties. 72. Lecompte Y, Evrard I, Arditti J. Metachlorophenylpiperazine (mCPP): a new designer drug .Therapie. 2006 Nov; 61(6): 523-30. 73. Pfpp. Drugs-Forum. [Internet] [cited 2015 May 2]; Available from: http://www.drugs- forum.com/forum/showthread.php?t=16084. 74. Berger M. Trifluoromethylphenylpiperazine-An Entheogenic Entactogen.[ Internet] Nov 2013[cited 2015 Mar] Available from: https://www.erowid.org/chemicals/tfmpp/tfmpp_article1.shtml. 75. Rösner et al. Isomeric Fluoro-methoxy-phenylalkylamines: a new series of controlled- substance analogues(designer drugs). Forensic Science International ,148( 2),143-56. [Internet] [cited 2015 Mar] Available from: http://www.fsijournal.org/article/S0379- 0738(04)00325-1/fulltext. 76. Geneva. Expert Committee on Drug Dependence. 4-Fluoromethcathinone(flephedrone;4- FMC) Critical Review Report;2014 June 16. Available from: http://www.who.int/medicines/areas/quality_safety/4_16_Review.pdf. 77. 3,4-Methylenedioxypyrovalerone(MDPV). Drug Enforcement Administration Office of Diversion Control Drug & Chemical Evaluation Section. [Internet] 2013 May[cited 2015 March 5]. Available from: http://www.deadiversion.usdoj.gov/drug_chem_info/mdpv.pdf 78. Mephedrone [Internet] [cited 2015 Mar 5] Available from: http://www.drugs- forum.com/forum/showwiki.php?title=Mephedrone. 79. Miranda von salis. Designer Drugs a New Problem for India's Young and Glamorous [ Internet] TalkingDrugs;2013 Mar 8 [cited 2015 Apr 5] Available from: http://www.talkingdrugs.org/designer-drugs-a-new-problem-for-indias-young-and- glamorous. 80. Money laundering and the drug trade the role of the banks. [Internet] [cited 2015 Apr 7]. Available from: http://www.globalresearch.ca/money-laundering-and-the-drug-trade-the- role-of-the-banks/5334205. 81. The Controlled Substances Act: Regulatory Requirements; Brian T. Yeh; Legislative Attorney ; December 13, 2012; https://www.fas.org/sgp/crs/misc/RL34635.pdf. Available from: http://news.softpedia.com/news/The-Effects-of-the-Drugs-on-Sex- Health-and-Social-Life-70913.shtml.

www.wjpps.com Vol 4, Issue 08, 2015. 335 Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences

82. NDPSACT.[Internet] Narcotics control bureau of India[Internet] [cited 2015 Apr 19] Available from: http://narcoticsindia.nic.in/NDPSACT.htm. 83. Colorimetric detection and chromatographic analyses of designer drugs in biological materials: a comprehensive review; Akira N, Akihiro N, Takeshi S, Masataka N; Forensic Toxicology, January 2011; 29(1): 1-24. 84. Fact sheet on new psychoactive substances. [Internet] UNODC World Drug Report;2013 [cited 2015 Apr 30] Available from: http://www.unodc.org/documents/southeastasiaandpacific//Publications/2013/wdr- 2013/Fact_Sheet_Chp2_2013.pdf.

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