Introduction
The term ‘drug abuse’ invites questions about what is a drug and what is the meaning of ‘abuse’. In a general sense, a drug is any substance without nutritional value which is capable of exerting a physiological or behavioral response in the subject. For the forensic drug examiner, as opposed to the toxicologist, this is much too broad. Following Paracelsus, we recognize all drugs as poisons, but the deliberate or accidental administration, including overdoses, of pharmaceutical medicines or the true poisons (e.g. carbon monoxide, cyanide, paraquat and arsenic) is not normally thought of as drug abuse. On the other hand, we should not conclude that the term is restricted to substances with medically useful properties. Most opinion asserts that cannabis, heroin and lysergide have little clinical value, yet they are widely abused. Alcohol and nicotine can lead to serious health and social problems, but there is much resistance in the wider community to even think of these substances as drugs.
For all practical forensic purposes, and for this discussion, drug abuse is largely concerned with those substances whose possession or supply is prohibited in law. We refer to them as the ‘scheduled’ or ‘controlled’ drugs. A few nonscheduled drugs are also of interest, but even here it is convenient to think of them as drugs which are potentially liable to be scheduled in the future. Expressions such as ‘illegal drug’ and ‘illicit drug’ are not always helpful. The former could include drugs which are perfectly legal when used in an appropriate context (e.g. morphine, benzodiazepines and other scheduled medicines), whereas ‘illicit’ refers to substances manufactured without licence and is not synonymous with ‘scheduled’. The use of labels such as ‘hard’ and ‘soft’ should also be avoided as they give the impression that some scheduled drugs are more acceptable than others. Although the expressions ‘abuse’ and ‘misuse’ are used interchangeably, the policy of the World Health Organization is to prefer the former if scheduled drugs are involved.
The legal classification of drugs is partly determined by their pharmacological properties. It is also convenient to group drugs according to their geographical origin, whether they are naturally occurring, semisynthetic or completely synthetic, their mode of administration, scale of abuse and physical form (e.g. powder, tablets, liquids).
In this article, drugs of abuse are described under three major headings:
• Form and origin Natural plant material Derived plant material Semisynthetic drugs Synthetic drugs
• Pharmacological classification Narcotic analgesics CNSstimulants Hallucinogens Hypnotics/tranquilizers Miscellaneous
• Legislative controls
Scheduled drugs: international classification The UN Single Convention on Narcotic Drugs,1961
The UN Convention on Psychotropic Substances,1971
National legislation Nonscheduled drugs
Form and Origin
Drugs of abuse fall into four groups: natural plant material, derived plant material, semisynthetic drugs and true synthetic drugs.
Natural plant material
Herbal cannabis or marijuana typically consists of the dried flowering tops of female Cannabis indica and related species, but it may also include the dried leaves. This plant has a widespread distribution, but grows best in subtropical conditions. Plants grown outdoors in Northern Europe rarely produce a good yield of flowers. The active principle in cannabis is tetrahydrocannabinol (THC), much of which is found in the resin surrounding the bracts. Cannabis is normally mixed with tobacco and smoked, but can be ingested. The average ‘reefer’ cigarette contains around 200 mg of herbal cannabis. The mean THC content of good quality cannabis is around 5%. Improved seed varieties, which have been selected to produce higher THC yields, are associated with intensive indoor cultivation. Procedures such as artificial heating and lighting, control of ‘day’ length, hydroponic cultivation in nutrient solutions and propagation of cuttings of female plants not only lead to a high production of flowering material, but the THC content may be in excess of 20% in ideal cases. At the other end of the scale, cannabis is also cultivated under license in a number of European countries for the production of fiber. The THC content of this cannabis is less than 0.3%.
The leaves of the coca plant (Erythroxylum coca), which grows on the Andean ridge in South America, have long been chewed by local people as a stimulant Coca leaves are also made into a commercially available coca tea, but this product is rarely seen outside South America. The active principle is cocaine.
Mescal buttons from the peyote cactus (Lopho-phora williamsii) originate from Central America and have had a long use in religious ceremonies. The active constituent is mescaline, an hallucinogenic phenethylamine. The peyote cactus is a slow-growing plant, which is rarely cultivated on a commercial scale. Mescaline has largely been superseded by synthetic phenethylamines (see below).
‘Magic’ mushrooms (Psilocybe semilanceata and related species) are another ubiquitous group. They contain the hallucinogenic tryptamines, psilocin, and its phosphate ester, psilocybin. The related hallucinogen, dimethyltryptamine, is a constituent of various tropical plants.
Khat or qat (Catha edulis) is a plant indigenous to Northeast Africa. The fresh leaves are chewed to extract both cathinone and cathine. These substances are stimulants closely related to ephedrine. Abuse of khat in Western countries is mostly confined to Ethiopian and Somalian communities.
Derived plant material
Cannabis resin (produced by collecting and compressing the resinous matter surrounding female cannabis flowers) has a typical THC content of 5%. Hash oil (a solvent extract of herbal cannabis or cannabis resin) may contain 30-40% THC.
Cocaine comprises around 1% of coca leaves. It is chemically extracted and manufactured into cocaine hydrochloride. This is a white powder which is commonly snorted. Some cocaine is reconverted to the free base. Known as ‘crack’, it is extremely addictive. Unlike the hydrochloride salt, it can be smoked.
Opium is also smoked, but abuse is uncommon in Western countries. It is the dried latex which exudes from the capsules of the opium poppy (Papaver somniferum), and contains around 10% morphine as the main active ingredient. Poppy straw concentrates, made by solvent extracting the dried capsules, are sometimes injected – a practice seen in Eastern Europe.
Semisynthetic drugs
Heroin is the most common example of a semisyn-thetic drug. It is produced by the acetylation of crude morphine obtained from opium. Until the late 1970s, nearly all of the heroin consumed in Europe came from Southeast Asia. Sometimes known as ‘Chinese heroin’, it was a white powder consisting of diamorphine hydrochloride and minor amounts of other opium alkaloids, but adulterants were unusual. However, over the past 20 years, most of the heroin seized in Europe has originated in Southwest Asia, an area centred on Pakistan, Afghanistan and Turkey. This material is a much cruder product, typically a brown powder containing around 45% diamorphine and variable amounts of other opium alkaloids (e.g. mono-acetylmorphine, noscapine, papaverine and acetyl-codeine). Adulterants are normally present, the most frequently reported being caffeine and paracetamol. It is generally accepted that most of these cutting agents are added to heroin at the time of manufacture. The illicit heroin used in North America traditionally originated from Southeast Asia, but in recent years Columbia has emerged as a major heroin supplier.
Synthetic drugs
Amphetamine was first synthesized over 100 years ago, but its stimulant properties were not recognized until much later. It is now rarely prescribed as a medicine, where one of its few uses is in the treatment of narcolepsy. In Europe, amphetamine is the second most commonly abused drug after cannabis. Most amphetamine syntheses continue to start with phenyl-2-propanone (benzyl methyl ketone). Despite international trade controls deriving from the United Nations (UN) 1988 Convention, illicit supplies of this and other precursors appear to be readily available on the black market. In North America and the Far East, methamphetamine is more common. This has traditionally been made from ephedrine, but trade controls have caused a shift to pseudoephedrine. More recently, phenylpropanolamine has been used in the USA to produce amphetamine. Both amphetamine and methamphetamine are found as white or off-white powders. Typical cutting agents are caffeine and sugars such as glucose. In Europe, amphetamine is occasionally seen in tableted form.
The ring-substituted amphetamines are commonly known as the ‘Ecstasy’ drugs. The prototypical member of this family is 3,4-methylenedioxymeth-amphetamine (MDMA). First synthesized in the early part of the twentieth century, abuse did not become widespread until the 1980s. Both amphetamine and MDMA are derived from the phenethylamine molecule. In the past 10 years, dozens of designer drugs based on variously substituted phe-nethylamine have appeared in Europe and the USA. These drugs are invariably produced in the form of white well-made tablets, often bearing a characteristic design (logo) and usually around 10 mm in diameter. The MDMA content of tablets is typically 80-90 mg. Lactose is a common excipient (filler) in tablets.
Lysergide (LSD) is generally thought of as a purely synthetic material, but routes of manufacture usually start from ergotamine, a natural substance produced by the microorganism Claviceps purpurea. Until the mid-1970s, LSD was produced in small (approximately 2 x 2 mm) tablets known as microdots. For the past 20 years, paper squares of around 7 x 7 mm have been the common dosage form. These squares are usually printed with a coloured design featuring cartoon characters, symbols or drug-related motifs; the lysergide content averages 50 ug.
Apart from lysergide and dimethyltryptamine (DMT), few synthetic drugs based on the tryptamine molecule have become popular, even though the synthesis and properties of many have been described in recent popular literature. A factor that is likely to limit the wider abuse of hallucinogenic tryptamines is their inactivity when taken orally. Most need to be smoked, injected or mixed with an ‘activator’ to inhibit metabolic destruction.
Methaqualone, a drug formerly used as a hypnotic, but now produced illicitly, has remained a popular drug of abuse in South Africa. It is often smoked mixed with cannabis.
Pharmacological Classification
The legal classification of an abused drug is determined by its propensity to harm the health of the individual or produce a risk to society. In large measure, these factors are governed by the pharmacological properties of the substance, particularly its toxicity and ability to produce dependence (a term used in preference to addiction). Most abused drugs fall into a few well-defined pharmacological categories, namely narcotic analgesics, central nervous system (CNS) stimulants, hallucinogens and hypno-tics/tranquilizers. A small number fall into a miscellaneous or mixed function group.
Narcotic analgesics
These are drugs which interact with those receptors in the brain responsible for the transmission of and response to pain. They may be differentiated from the peripheral analgesics (e.g. aspirin), which have no abuse potential. The classical narcotic analgesics are the opium alkaloids (principally morphine) and its semisynthetic derivatives (e.g. diamorphine – the main active principle in heroin, codeine, buprenor-phine). In the first half of the twentieth century, a large group of entirely synthetic narcotic analgesics was developed, including methadone, pethidine (meperidine) and fentanyl. Abuse of narcotic analgesics is responsible, by far, for most drug-related mortality and morbidity.
CNS stimulants
Although the narcotic analgesics may cause the greatest damage to society and the individual, the CNS stimulants are probably the most widely abused. These drugs have a close structural relationship to neurotransmitters such as dopamine and noradrena-line. They are believed to act on receptors in the brain and other tissues, causing an increase in the levels of these neurotransmitters. This results in a rise in blood pressure, increased mental alertness and wakefulness, reduction of physical fatigue and appetite. Prolonged use can lead to psychosis. In developed countries, amphetamine, methamphetamine and cocaine are the commonly encountered examples. In some countries, there is abuse of medicinal drugs nominally intended for the treatment of narcolepsy, weight reduction or hyperactivity attention disorder (e.g. diethylpropion, pemoline, methylphenidate).
Hallucinogens
Naturally-occurring hallucinogens have been used in Central and South America since historical times. The most common of these are mescaline, dimethyl-tryptamine and other ring-substituted tryptamines such as psilocin. These drugs produce visual and other sensory hallucinations. Synthetic hallucinogens are typified by lysergide. It is one of the most potent drugs to act on the CNS. Although first produced over 50 years ago, serious abuse was uncommon before the 1960s. This era also saw the appearance of other clandestine hallucinogens such as DOB (brolamfetamine, 4-bromo-2,5-dimethoxy-a-methyl-phenethylamine). More recently, other hallucinogenic phenethylamines have received wide publicity. These drugs, sometimes known as psychedelics, are thought to act by interfering with serotonin receptors in the brain. As with the stimulant drugs, there is a close relationship between the chemical structure of hallucinogenic drugs and serotonin (5-hydroxy-N,N-dimethyltryptamine).
Hypnotics/tranquilizers
The barbiturates were once the most commonly used hypnotic drugs, but are now rarely prescribed or abused. Their CNS depressant properties led to many deliberate and accidental overdoses. They have been replaced by the benzodiazepines – a group which spans a range of both hypnotic (sleep-inducing) and tranquilizing properties. Benzodiazepine tranquilizers are typified by diazepam and lorazepam. Although these drugs may often be found in impaired vehicle drivers, abuse is largely restricted to the hypnotic members (e.g. flunitrazepam and temazepam). However, the distinction between the two types is largely based on their potency and duration of action.
Miscellaneous
The so-called ‘Ecstasy’ drugs are sometimes described as hallucinogenic, but their effects are unlike those of LSD. Although MDMA and its congeners may show some stimulant properties, they have been described as falling into the novel pharmacological categories of ‘entactogens’ and ‘empathogens’. The pharmacological effects of cannabis are fairly diverse, as may be expected from a complex plant product. Effects include euphoria, sedation, analgesia and hallucinations. Most abused solvents fall into the category of simple anesthetics, although substance-specific effects have been reported. Anabolic steroids are abused for their ability to increase lean body weight, strength and overall physical fitness.
Legislative Controls: Scheduled Drugs: International Classification
UN Single Convention on Narcotic Drugs, 1961
Plant-based drugs, such as opium, cannabis and cocaine, have been used for thousands of years, but the concept of drug abuse is much more recent. As a consequence of social change, the problem has inevitably arisen from a situation where the drug in question was initially accepted, at least in certain populations, if not actively promoted by commercial interests. This was the position with opium towards the end of the nineteenth century. Following the meeting of the Shanghai Opium Commission in 1909, trade was curtailed and eventually replaced by legislative sanctions against supply and use. Cocaine was once a permitted additive in Coca-Cola, whereas heroin (diacetylmorphine) was marketed as a treatment for opium addiction.
The major plant-based drugs have now been variously controlled for many years, but the modern era of international legislation starts with the UN Single Convention on Narcotic Drugs in 1961. Member States which are signatories to the Convention will have established the principles in domestic legislation. The Convention maintains a strong emphasis on these same plant-based drugs, setting out rules for their cultivation, manufacture and trade. However, the scope of control was widened to include over 100 mostly synthetic substances, the great majority of which can be described as narcotic analgesics; few of these are now used clinically or ever abused. The drugs are set out in four Schedules. Most are found in Schedule I, the category with the greatest restrictions. The more commonly encountered drugs in forensic casework, which are included in the 1961 Convention, are set out in Table 1.
UN Convention of Psychotropic Substances, 1971
During the 1960s, the abuse of stimulants, hallucinogens and related drugs became a problem in many Western societies. These drugs were often abused in the form of pharmaceutical preparations. Just as with the plant-based drugs in a previous era, the supply of stimulants was promoted by commercial concerns as aids to weight control and relief from fatigue. Even hallucinogens, such as LSD, were legitimized by their use in psychiatry. The 1971 UN Convention on Psychotropic Substances was intended to deal with this phenomenon. Again, the drugs for control were set out in four Schedules. Whereas a forensic drugs examiner is unlikely to encounter the great majority of substances in the 1961 Convention, the psycho-tropic drugs in the 1971 Convention will be more familiar. There are over 100 substances listed; Table 2 shows the more commonly encountered drugs in the four Schedules. Unlike the 1961 Convention, there is no overarching control of isomers. This leads to a situation in which a generic term such as amphetamine (meaning both the ‘ —’ and the ‘+’ enantiomers)
Table 1 The more commonly encountered drugs of abuse listed in the 1961 UN Single Convention on Narcotic Drugs
Schedule I
Cannabis and cannabis resin and extracts and tinctures of
cannabis Coca leaf Cocaine
Concentrate of poppy straw
Dextromoramide
Dipipanone
Heroin (diacetylmorphine)
Methadone
Morphine
Opium
Pethidine
The isomers, esters and ethers (unless appearing in another Schedule) and the salts of the drugs listed in this Schedule
Schedule II
Codeine Dihydrocodeine
The isomers and the salts of the drugs listed in this Schedule
Schedule III
This is concerned with what may be termed ‘low-dose’ preparations of drugs already listed in Schedules I or II. For example, it includes: codeine or dihydrocodeine when compounded with one or more other ingredients and containing not more than 100 mg of the drug per dosage unit and with a concentration of not more than 2.5% in undivided preparations; cocaine preparations containing less than 0.1% cocaine; and morphine preparations containing less than 0.2% morphine
Schedule IV
This is a list of those Schedule I substances which, unlike most of the entries in Schedule I, are considered to be of limited medicinal value and should be restricted to research use. It includes, among others, cannabis and cannabis resin and heroin
Table 2 The more commonly encountered drugs of abuse listed in the 1971 UN Convention on Psychotropic Substances
Schedule I
Brolamphetamine (DOB) Cathinone
Dimethyltryptamine (DMT)
W-Ethyltenamphetamine (MDE)
W-Hydroxytenamphetamine (W-OH MDA)
Lysergide (LSD)
MDMA
Mescaline
Psilocin
Psilocybin
Tenamphetamine (MDA)
Schedule II
Amphetamine
Dexamphetamine
Dronabinol
(+)-Methamphetamine
Methamphetamine racemate
Methaqualone
Methylphenidate
Phencyclidine
Secobarbitone
Schedule III
Amobarbital Buprenorphine Cathine Pentobarbital
Schedule IV
Diazepam and many other benzodiazepines
Diethylpropion
Pemoline
Phenobarbitone
The salts of the substances listed in all four Schedules sits alongside dexamphetamine (i.e. the ‘+’ enantio-mer of amphetamine).
National legislation
Nearly all States limit their domestic controls to those substances listed in the 1961 and 1971 UN Conventions. A few countries have chosen to control a wider range of drugs. For example, certain anabolic steroids are controlled in the UK and the USA, although the substances named are not identical in the two countries. In the UK, 48 anabolic steroids are listed specifically as Class C drugs (the lowest category), and generic legislation covers certain derivatives of 17-hydroxyandrostan-3-one or 17-hydroxyestran-3-one as well as the esters or ethers of the named steroids. In the UK, the more commonly encountered controlled steroids are methandienone, nandrolone, oxymetho-lone, stanozolol, and testosterone and its esters.
Further anabolic nonsteroidal compounds are also controlled, i.e. human chorionic gonadotrophin (hCG), clenbuterol, nonhuman chorionic gonadotro-phin, somatotropin, somatrem and somatropin.
Starting in the late 1970s, the UK introduced a number of generic definitions into the Misuse of Drugs Act of 1971. Thus, apart from derivatives of certain steroids as noted above, suitably substituted derivatives of tryptamine, phenethylamine, fentanyl, pethidine and barbituric acid also became controlled. A broadly similar approach is used in New Zealand. In the USA, the problem of so-called ‘designer drugs’ has been effectively dealt with by the Controlled Substances Analogue Enforcement Act of 1986.
In the UK legislation, apart from a few exceptions, no distinction is made between the isomers of listed drugs. Thus the Misuse of Drugs Act lists amphetamine, but not dexamphetamine, which is considered redundant. By contrast, in the USA, offenses involving different isomers of, for example, methamphet-amine may attract different penalties.
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 Psycho-tropic 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.
