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Designer Drugs: a Review 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 DRUGS: A REVIEW Dr. Suyash Chavan,MBBS*1 and Dr. Vandana Roy2 1MD, Resident Doctor, Department of Pharmacology, 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 drug 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, Bath salts, 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, www.wjpps.com Vol 4, Issue 08, 2015. 297 Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences 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, morphine was isolated from opium and heroin was synthesized from morphine. In the early 1900s, cocaine 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 opioid 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, amphetamines and barbiturates 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 www.wjpps.com Vol 4, Issue 08, 2015. 298 Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences structure of LSD. This structural modification increased their potency and prevented them from being detected in drug tests.[6] The anaesthetic agent Phencyclidine emerged as a new club drug (angel dust) during the 1970s. Fentanyl structure based new Opioid drugs, Anabolic steroids and stimulant drugs like Methamphetamine 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 cannabinoids, synthetic cathinones, piperazines and phenethylamines 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] www.wjpps.com Vol 4, Issue 08, 2015. 299 Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences 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 Amphetamine-type stimulants and their trade to European countries. Codeine-based cough syrups, dextropropoxyphene, benzodiazepine, buprenorphine and pethidine 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 designer drug 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 opioids (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. Dissociatives 7. Piperazine-based 8. Stimulants www.wjpps.com Vol 4, Issue 08, 2015. 300 Chavan et al. World Journal of Pharmacy and Pharmaceutical Sciences Nomenclature Based upon the chemical structure, the drugs have been given names by the IUPAC (The International Union of Pure and Applied Chemistry). 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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