DRUGS OF ABUSE | Designer Drugs

DRUGS OF ABUSE | Designer Drugs

DRUGS OF ABUSE/Designer Drugs Some countries have scheduled specific substances either for legislative convenience or because the drugs are deemed to...

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DRUGS OF ABUSE/Designer Drugs

Some countries have scheduled specific substances either for legislative convenience or because the drugs are deemed to be a local problem. An example of the former is the inclusion of ephedrine as a controlled drug in the Republic of Ireland. (This arose from a desire to consolidate into their Misuse of Drugs Act of 1977 the provisions of the UN 1988 Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.) An example of the latter is the control of the khat plant in the USA and a number of European countries.

Nonscheduled Drugs Apart from drugs under international or domestic control, there is a further small group of substances that are recognized as causing personal and social problems, particularly in Europe and North America. These are possible candidates for control, but as discussed earlier should be distinguished from `socially acceptable' substances such as alcohol, nicotine and caffeine. Ketamine and gamma-hydroxybutyrate (GHB) are both under investigation in the UK and USA as candidates for control. Ketamine is used in veterinary and some human surgery as an anesthetic. Only injection solutions are licensed, whereas abusers ingest powders and tablets, sometimes mixed with a stimulant such as ephedrine to mimic the effects of MDMA. GHB is licensed for use in some countries as a hypnotic, but it is also abused. Not only is GHB readily made from its precursor (gamma-butyrolactone), but that precursor is widely used as an industrial solvent which is metabolically converted to GHB. Abuse of solvents by inhalation is arguably a more serious problem, which leads to many fatalities. However, hydrocarbons, such as butane and toluene, are so readily available that effective control would prove difficult to achieve. The alkyl nitrites, which cause peripheral vasodilation, represent a particular type of solvent abuse, but again their control would present practical problems. Finally, there are numerous herbal drugs which are abused for their stimulant or hallucinogenic properties. Not only is this somewhat of a fringe activity, but most legislatures are reluctant to control a wider range of plant material. See also: Drugs of Abuse: Designer Drugs. Pharmacology.

Further Reading Advisory Council on the Misuse of Drugs (1998) Drug Misuse and the Environment. London: Stationery Office.

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British Medical Association (1997) The Misuse of Drugs. Amsterdam: Harwood. European Monitoring Centre for Drugs and Drug Addiction (1998) Annual Report on the State of the Drugs Problem in the European Union. Luxembourg: Office for Official Publications of the European Communities. Fortson R (1996) The Law on the Misuse of Drugs and Drug Trafficking Offences, 3rd edn. London: Sweet and Maxwell. Hardman J (eds) (1996) Goodman and Gilman's Pharmacological Basis of Therapeutics. New York: McGrawHill. Henry J (1994) The British Medical Association New Guide to Medicines and Drugs. London: Dorling Kindersley. Institute for the Study of Drug Dependence (1999) Drug Abuse Briefing: A Guide to the Non-Medical Use of Drugs in Britain, 7th edn. London: ISDD. Julien RM (1995) A Primer of Drug Action, 7th edn. New York: Freeman. Karch SB (eds) (1998) Drug Abuse Handbook. London: CRC Press. Ramsay M and Spiller J (1997) Drug Misuse Declared in 1996: Latest Results of the British Crime Survey. London: Home Office. Redda KK, Walker CA and Barnett G (ed.) (1989) Cocaine, Marijuana, Designer Drugs, Chemistry, Pharmacology and Behavior. Boca Raton, FL: CRC Press. Stockley D (1992) Drug Warning. London: Optima. United Nations (1993) Multilingual Dictionary of Narcotic Drugs and Psychotropic Substances under International Control. New York: United Nations. United Nations International Drug Control Programme (1997) World Drug Report. Oxford: Oxford University Press. Webber D (ed.) (1998) Controlled Drugs: A Handbook for the Legal Profession. London: Institute for the Study of Drug Dependence.

Designer Drugs J Hartelius, Stockholm, Sweden Copyright # 2000 Academic Press doi:10.1006/rwfs.2000.0495

Emergence of the Concept The concept of `designer drugs' gained attention in the 1980s as a new expression for describing a number of recent arrivals among the psychoactive

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substances on the illegal drug markets. When introduced for intoxicating purposes, the substances in many cases escaped formal drug control, such as the Controlled Substances Act (US), the Misuse of Drugs Act (UK) or the Narcotics Control Act (Sweden); nor were they regulated under the United Nations International Drug Conventions (Single Convention on Narcotic Drugs, 1961; Convention on Psychotropic Substances, 1971). Thus, they were rapidly perceived by public authorities to constitute a challenge to traditional drug control. The concept of designer drugs is generally attributed to Dr Gary L. Henderson of the University of California at Davis, who introduced the concept to describe new, untested, legal synthetic drugs mimicking the effects of illicit narcotics, hallucinogens, stimulants and depressants. The concept has, however, no established scientific or codified judicial definition. Instead, several definitions have been advanced: most converge on the following criteria, stating that designer drugs are: 1. psychoactive substances; 2. synthesized from readily available precursor chemicals; 3. marketed under attractive `trade marks' (fantasy names); 4. not subjected to legal control as narcotic drugs or psychotropic substances, at least not at the time of their introduction on the nonmedical drug market. Sometimes the following criteria are added: 5. being produced mainly or exclusively in clandestine laboratories; 6. having little or no established medical use. In common parlance, a designer drug can be said to be a synthetic psychoactive substance having pharmacologic effects similar to controlled substances and initially remaining outside traditional drug control. Sometimes, these drugs are referred to as analogs, analog drugs or homologs, to stress the analogy or homology of their pharmacologic properties (and chemical structure) to well-known controlled substances. In media reporting, the concept also has a connotation of novelty: the drugs are seen as modern creations in the same sense as designer clothes in fashion. Some designer drugs have nevertheless been known for decades: the process for synthesizing 3,4-methylenedioxymethamphetamine (MDMA) was patented in 1914. The demarcation of the substances regarded as designer drugs is not universally accepted. Sometimes `old timers', such as methamphetamine (widely abused in Japan in the 1950s), are included. The

concept is fluid and dynamic, mirroring a continuous search for new psychoactive substances. The pioneer in this field is the American pharmacologist and chemist Alexander Shulgin (b. 1925), who for decades has been synthesizing and investigating the effects of hundreds of such substances. Some designer drugs have also been studied experimentally in cult-like settings in religiously flavored attempts to experience altered states of human consciousness.

Issues of Forensic Interest Designer drugs raise at least four issues of forensic interest: 1. Determination of the chemical composition of new substances on the illegal drug market, such as when `Hog' in 1968 was shown to be phencyclidine (PCP). 2. Problems of detecting very low concentrations (p.p.b. range) of a substance in body fluids in cases of severe intoxication or fatal poisoning. Sometimes the health hazard may come from impurities, such as 1-methyl-4-phenyl-1,2,5,6tetrahydropyridine (MPTP) in the synthesis of 1methyl-4-phenyl-4-piperidyl propionate (MPPP) as a heroin substitute resulting in severe parkinsonism (the worst cases known as `frozen addicts'). The drugs have also be used secretly to intoxicate or sedate a person for aims of sexual abuse or robbery. The detection problem is aggravated by the fact that new substances may not be fully investigated in respect of metabolites and routine methods of detection. 3. Determination of the particular substance used in a case of individual drug intoxication, especially when police diagnostic methods (such as the American drug recognition expert (DRE) wayside procedures) are used, as some designer drugs may not be controlled substances within the scope of domestic drug legislation. 4. Strategies to be used for controlling new drugs, e.g. drug scheduling, when a large number of new and unknown substances appear on the market. The number of designer drugs that can be produced in clandestine laboratories has been estimated to be from 1000 upwards, depending on the competence and resources of the chemist.

Major Types of Designer Drugs Designer drugs can be classified, in the same way as other psychoactive drugs, into depressants, stimulants, hallucinogens, etc. More commonly, they are

DRUGS OF ABUSE/Designer Drugs

classified according to their basic chemical structure, such as fentanyls or phenetylamines. The most important contemporary designer drugs are to be found among the following classes. Fentanyls

These have the same major properties as opiate narcotics, and they are used in medicine mainly as anesthetics or analgesics (Fig. 1). They are, however, much more potent; some varieties are estimated to be 20± 4000 times as potent as heroin. They may produce intoxication even in the microgram range. One gram (1 g) may be sufficient for 10 000 doses. Because of their extreme potency, fentanyls may be difficult to dilute for street sale as intoxicants. Their clandestine synthesis may be extremely profitable: precursors costing USD 200 may produce drugs at a value of USD 2 000 000 on the illicit market. Alphamethylfentanyl, diluted and sold under the name `China White' to mimic traditional heroin of extreme purity, was among the first designer drugs to appear on the market (1979) and rapidly caused a number of overdose deaths. The number of drugs in this class is estimated to be around 1400, and the total number of designer opiates 4000. Methcathinone analogs

The khat (kath, qat) plant (Catha edulis) contains the central nervous system stimulants cathin (norpseudoephedrine) and cathinone. They are both under international control as psychotropic substances, but not the plant per se. Methcathinone (ephedrone) is a synthetic analog of cathinone, and it can easily be produced in a `kitchen laboratory' (Fig. 2). It is highly dependence- and tolerance-forming, and it is often abused in `binges' with intensely repeated administration for several days. Its main effects include severe anorexia, paranoia and psychosis. Homologs

Figure 1 Fentanyl. Reprinted from Valter K, Arrizabalaga P (1998) Designer Drugs Directory with permission from Elsevier Science.

Figure 2 Methcathinone. Reprinted from Valter K, Arrizabalaga P (1998) Designer Drugs Directory with permission from Elsevier Science.

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of methcatinone, some of which are not under formal drug control, are considered by some to represent a potentially new series of designer drugs yet to be introduced to the nonmedical market. The number of drugs in this class is estimated to be around 10. Phencyclidines

These have both anesthetic and hallucinogenic properties. PCP was originally developed in the 1950s as an anesthetic (Sernyl), but it was withdrawn after it was found to produce severe hallucinations in patients (Fig. 3). Ketamine (Ketalar, Ketanest) is still used as an anesthetic, but it is also abused for its alleged ability to produce a meditative state. Drugs of this type may cause depression, psychosis, personality changes and overdose deaths. The confounding of anesthetic and hallucinogenic properties may make the abuser very difficult to handle in confrontations with the police. The number of drugs in this class is estimated to be 50. Phenetylamines (PEAs)

These comprise a large group, including such highly diverse substances as amphetamine and mescaline. These drugs can be divided into two subgroups: mainly euphoriant or mainly hallucinogenic. Among the euphoriant PEAs, the most widely known and abused one is MDMA (this was the original `Ecstasy' drug, but this name has also been applied to new varieties such as 3,4-methylenedioxyamphetamine (MDA) and N-ethyl-3,4-methylenedioxyethylamphetamine (MDEA)) (Fig. 4). It has become especially popular among young people at `rave' and `techno' parties. Sometimes these drugs are labeled `entactogens' for their alleged ability to increase sensitivity to

Figure 3 Phencyclidine. Reprinted from Valter K, Arrizabalaga P (1998) Designer Drugs Directory with permission from Elsevier Science.

Figure 4 MDMA. Reprinted from Valter K, Arrizabalaga P (1998) Designer Drugs Directory with permission from Elsevier Science.

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Piperidine analogs are mainly MPPP, MPTP, OPPPP (1-(3-Oxo-3-phenylpropyl)-4-phenyl-4-piperidinol propionate) and PEPAP (1-Phenethyl-4-phenyl-4piperidol acetate (ester)) (Fig. 5). They have both euphoriant and analgesic properties. They may cause, for example, convulsions and respiratory depression. MPPP is a powerful analgesic but it has never been used in clinical medicine. MPTP has been identified as the causative agent of the frozen addicts syndrome. The number of potential drugs in this class has not been estimated.

services. In reviewing the problem, one author wrote that `Designer drugs are subverting the black-market drug trade, undermining and subverting law enforcement activities, and changing our basic understanding of drugs, their risks and the marketplace itself.' As only a small number of the thousands of varieties of designer drugs have appeared on the nonmedical market, it is likely that many more will be introduced, tested, abused and, ultimately, administratively controlled. Over the next years, the emergence of new designer drugs will raise important control issues, such as the criteria and procedures to be used for extending drug control to new substances. This may call for a new definition of drugs (controlled substances), not solely based on administrative drug scheduling but also on the pharmacological properties of the new drugs. Designer drugs will also raise complicated scientific and medical issues, such as new methods for identifying hazardous substances and treating severe intoxications. They may open new vistas for brain research. A substantial increase in clandestine production of designer drugs may change the structure of the illegal drug market, making some established forms of production (e.g. heroin from opium poppy) obsolete.

Tryptamines

See also: Pharmacology.

Tryptamines (indolealkylamines) include drugs such as dimethyltryptamine, harmaline, lysergide (LSD) and psilocybine. They produce a variety of reactions, including hallucinations and tremor. LSD was the center of a psychedelic cult in the 1960s, being used for its alleged `mind-expanding properties'. The number of LSD analogs is estimated to be 10 and the number of psychotomimetic indolealkylamines is estimated to be several hundred.

Further Reading

touch, or `empathicogens', for their alleged ability to create empathy, especially before sexual encounters. They may cause severe neurotoxic reactions due to serotonin depletion (e.g. depression, suicidal behavior and personality changes) and, when taken in connection with physical exercise such as dancing, even rapid fatalities. The predominantly hallucinogenic (psychotomimetic) PEAs include e.g. DOB (4Bromo-2,5-dimethoxyamphetamine), DOM (2,5Dimethoxyamphetamine), and TMA (3,4,5-Trimethoxyamphetamine). These drugs may cause or trigger psychotic reactions. The total number of drugs in this class is estimated to be several hundred. Piperidine analogs

Trends and Control Issues The modern designer drugs represent a new phase in drug synthesis and drug abuse. They have caused fundamental problems for contemporary administrative drug control, forensic investigation and medical

Figure 5 MPPP. Reprinted from Valter K, Arrizabalaga P (1998) Designer Drugs Directory with permission from Elsevier Science.

Dal Cason TA (1997) The characterization of some 3,4methylenedioxycathinone (MDCATH) homologs. Forensic Science International 87:9±53. Holmstedt B (1969) Gas chromatography±mass spectrometry as a tool to elucidate the structure of unknown psycho-active drugs. In: SjoÈquist F and Tottie M (eds) Abuse of Central Stimulants, pp. 357±373. Stockholm: Almquist and Wiksell. Kalix P (1984) The pharmacology of khat. General Pharmacology 15:179±188. Klein M, Sapienza F, McClain H and Khan I (1989) Clandestinely Produced Drugs, Analogues and Precursors. Proceedings of an International Conference, 8±11 September 1987, Rabat, Morocco. Washington, DC: WHO/Drug Enforcement Administration. Kirsch MM (1986) Designer Drugs. Minneapolis: CompCare. Shulgin A and Shulgin A (1991) PiHKAL ± A Chemical Love Story. Berkeley, CA: Transform Press. Shulgin A and Shulgin A (1997) TiHKAL ± The Continuation. Berkeley, CA: Transform Press. Valter K and Arrizabalaga P (1998) Designer Drugs Directory. Lausanne: Elsevier.