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Over the past decade, the widespread use of ‘recreational’ drugs has been increasingly acknowledged. In a burst of revelation last year, politicians of various hues confessed to having used illegal substances—in their younger days. The police tell us that a substantial proportion of certain crimes are drug-related, and there is debate on whether the laws on drug use need to be modified. Meanwhile, governments have announced ‘war’ on drugs, and ‘drug czars’ have come on the scene.
The debate on drugs is not always well informed. Anyone who seeks good information on the subject would do well to consult the writings of Steven Karch, an American pathologist with many years of research experience in the area. I have regularly turned to his textbook Pathology of Drug Abuse in its two previous editions. A third edition was eagerly awaited, because knowledge of drug effects has increased and patterns of use have changed. For instance, methylenedioxymethylamphetamine (MDMA, ‘ecstasy’), which originally reached Europe from America, has lately recrossed the Atlantic while cocaine is gaining ground on this side of the pond. In launching the third edition, Karch's publishers have saluted the author with an eponymous title—Karch's Pathology of Drug Abuse1. The book is longer than its predecessor of six years ago and has an additional 800 references. It is not just about pathology; also covered are the toxicology and clinical effects of the drugs, as well as epidemiological data, drawn mostly from DAWN (Drug Abuse Warning Network) surveys. DAWN provides data on drug deaths in the USA. Of great interest are the historical introductions to each major group of substances.
Do not turn to this work for information on either alcohol or marijuana. The first is very reasonably excluded because it requires its own textbook; the second because there are too few data on pathological effects. Cocaine is the subject of the first chapter, 187 pages long. Karch has a special interest in this drug, which in DAWN surveys was the commonest cause of drug-related death (in the UK, the commonest cause is heroin). He begins with history. The purification of cocaine led to a wide range of medical and non-medical uses; it became a popular additive to wine and was used as a treatment for morphine addiction—a strategy promulgated by Freud though first recommended by American physicians. Cocaine was not the only newly discovered agent to follow such a course: for example, amphetamines were recommended for seizures, schizophrenia, multiple sclerosis, head injuries, migraine, radiation sickness and morphine addiction, and heroin was sold as a cough suppressant. Cocaine toxicity was soon recognized, but many of the ill-effects had to be rediscovered when use of this agent exploded in more recent times.
One matter dealt with throughout the book is the interpretation of toxicological findings. For example, a chronic drug user who dies of a non-drug-related cause, such as being shot, may have a much higher concentration of the drug than someone who has died of an overdose. There is also the complication of post-mortem drug redistribution: thus, samples taken from separate anatomical areas may have widely different concentrations of drug; what then, is a fatal drug concentration? A very detailed description of cardiovascular pathology and cocaine includes discussion of deaths during arrest and in custody, and the contribution of postural asphyxia, excited delirium and other factors surrounding these often high-profile events.
After cocaine comes an examination of naturally occurring stimulants, including absinthe (a popular drink in the 19th century and before, and now enjoying something of a come-back in the UK), caffeine, ephedrine and khat. Khat, a plant that grows in parts of Africa, is a legal substance in the UK but illegal in the USA. The leaf (which is chewed) contains a stimulant, cathinone, similar to amphetamine; like amphetamine it can be associated with development of a psychotic illness. Ephedrine was used as a treatment for asthma and is a constituent of certain food supplements (‘herbal ecstasy’). It was given to kamikaze pilots in the Second World War and ephedrine abuse was widespread in post-war Japan. Today it is used as a precursor chemical in the illicit manufacture of amphetamine and methamphetamine. In America methamphetamine is increasingly important in drug-related deaths, but this agent (in contrast to amphetamine) is seldom encountered in the UK. This chapter also deals with misuse of methylphenidate (Ritalin). All the evidence indicates that, as with methadone, methylphenidate is diverted from clinical use rather than being illicitly manufactured.
The chapter on hallucinogens includes mescaline, MDMA and similar compounds, phenylalkalines such as psilocybin (the psychoactive compound in ‘magic mushrooms’) and lysergic acid diethylamide (LSD). The MDMA section has been much expanded from the previous edition, reflecting the now widespread use of these drugs and the concomitant increase in published reports. Another agent discussed in this chapter is bufotenine. This substance was the active component of certain hallucinogenic snuffs described by 16th century explorers of the Amazon. It is famously present in certain species of toad, giving rise to use of bizarre toad products as hallucinogens.
Opiates are awarded 142 of the book's 541 pages. Opium was mentioned by Homer and artifacts relating to opium predate the poet by a thousand years. Abuse of the drug has a long history, including Britain's war with China to maintain her opium trade. Karch records the advent of the hypodermic syringe, which advanced the use and abuse of opium products. Whilst credited to the Scottish physician Wood, the idea was first suggested by Christopher Wren, who as well as being an architect and astronomer was a physician. Wren experimented by injecting dogs with opium. Another important event in the history of opiate abuse was the synthesis of heroin, by CR Wright at St Mary's Hospital in London in 1874. By the 1920s heroin abuse was so troublesome that the American Medical Association voted to prohibit importation of the substance. The first necropsy report of an opiate death was in 1852, but this has never been a popular subject for pathological study. Despite the large number of deaths in the 1990s, the interval between the first and third editions of Karch's book (ten years) saw only twelve new papers recording microscopical findings in opiate deaths.
A new chapter, on disassociative anaesthetics, includes descriptions of the effects of phencyclidine (PCP) and the chemically related ketamine and γ-hydroxybutyrate (GHB). These compounds have hallucinogenic properties. PCP first appeared in California in the 1960s. Its popularity in the USA has declined and it is not currently encountered in the UK. However, ketamine, which was developed as a legitimate anaesthetic, is well known on the dance scene under the name of ‘special K’. GHB, currently lawful in the UK, is likewise increasingly encountered on the dance scene and has been used as a ‘date rape’ drug. This agent has been associated with several deaths, particularly when combined with alcohol. It is produced in the body after death, so interpretation of post-mortem toxicological findings can be complex. Because of its property of stimulating growth hormone release, GHB has been popular with body builders. Anabolic steroids, another staple of body builders and athletes, are discussed in a separate chapter. The book also gives proper attention to solvent abuse, an often neglected but important cause of morbidity and mortality in which the victim is typically younger than in other forms of substance abuse.
Karch's book is well illustrated and extensively referenced. The appendices include useful tables on heart weights, volume distribution and blood alcohol concentration estimates and conversion formulas for drug concentrations. I warmly recommend it to anyone who deals in any capacity with the effects of substance misuse.