Abstract
Left: Oral methadone. Courtesy of the Geoffrey Kaye Museum of Anaesthetic History. Right and above: Scientist at Lexington Hospital mapping the brain to learn the effects of many abused substances and the causes of addiction. Courtesy of the US National Library of Medicine.
There is an exclusive wing of Lexington reserved for the Do-Rights, who are considered good rehabilitation prospects. They get better rooms and more medication.
William S Burroughs (1914–1997), ‘The Do-Rights’, date unknown.
William Burroughs, a hugely influential post-modern American author, visual artist and member of the Beat generation, appeared in many recordings and films. He drew much of his inspiration from his own life, especially his long struggle with heroin addiction. The Lexington Narcotic Farm in Kentucky featured in several of his novels and song lyrics, and these reflect his cynicism with a place that seemed to him to support, rather than cure, his addiction. Like many voluntary patients, Burroughs only stayed long enough to try a few new experimental drugs before discharging himself when the drug withdrawal phase of the treatment started.
Most residents were not voluntary though—they were drug-addicted federal prisoners. The Lexington Narcotic Farm opened in 1935, one of two new, experimental facilities for the ‘confinement and treatment of persons addicted to the use of habit-forming narcotic drugs’. 1 Opium and its various derivatives had been largely unregulated throughout the nineteenth century but as awareness of the addictive properties of these drugs grew, organisations and therapeutic regimens developed. 2 Eventually governments felt compelled to intervene, and in the United States a series of state and federal interventions were enacted from 1880 onwards. 3 These regulations culminated in the Harrison Narcotic Tax Act of 1914, often seen as the beginning of the US government’s war on drugs.
At the time, the US pharmaceutical industry was conspicuously lagging behind the rest of the world. 4 To address this deficit, the National Research Council formed the Committee on Drug Addiction (CDA) under the auspices of the New York City Bureau of Social Hygiene in 1921. The CDA was created specifically to identify non–habit-forming opiates and local anaesthetics. They originally believed that ‘the opium problem’ resulted largely from medical use leading to addiction, but investigators soon came to appreciate that there was also a rising use of recreational heroin in the community.
The CDA studied the morphine molecule in detail, seeking to separate the analgesic properties from the addictive properties and manipulate the molecule to produce a potential alternative. But to conduct clinical trials they needed drug-addicted patients. In 1929, US Congress authorised the construction of ‘narcotic farms’, with the first being built in Lexington, Kentucky. 4 When it opened six years later, it housed 1500 inmates and a small research laboratory.
The scientists at Lexington began by studying the withdrawal process in 65 patients, concluding that ‘morphine abstinence syndrome is a definite clinical entity’. 5 The research director, Clifton Himmelsbach, developed a scoring system to quantify the patient’s dependence—known as the ‘point system for measuring abstinence syndrome intensity by the day or by the hour’.5,6 Single points were given for symptoms such as yawning and perspiration and up to five points for restlessness and emesis; the points were added to produce a single score. Various symptomatic treatments such as warm baths, intravenous fluids and sedatives were adopted and a programme of treatment evolved. Initially patients were stabilised for a week or so on a known dose of opioid, accepting that the street drugs they had been consuming were of uncertain strength and quality. Then the withdrawal process would begin with symptomatic treatments or, as morphine substitutes became available, in clinical trials with these experimental drugs. Withdrawal from the opioid substitutes could then also be quantified with the point system.
In the early years, of the 150 compounds they produced, only Metopon (5-methylhydromorphone) met most of their criteria. Metopon was marketed for chronic pain until the early 1950s and was considered the drug which proved that pain relieving properties could be dissociated from the addictive properties and respiratory depression. Despite this, it did not fulfil the requirement for a drug with ‘long and strong analgetic action, but a short and weak dependence effect … ideal for clinical purposes’. 6
The next drug to show promise in the area was methadone, a drug developed in the laboratories of IG Farbenkonzern in Frankfurt during the Second World War as an antispasmodic.7,8 Once the war ended, German patents were declared invalid and methadone was produced commercially by Eli Lilly and Co. in the United States as dolophine. Early clinical trials showed little benefit over morphine as an analgesic, 9 but it was extensively studied and used in addiction medicine. Trials at Lexington under the new research director, Harris Isbell, concluded that methadone produced a milder, more prolonged version of the morphine abstinence syndrome. In 1948, methadone was included in the opioid detoxification programme although they remained concerned that ‘narcotic drug addicts would abuse amidone [methadone] if it were freely available’. 10
These concerns hampered research throughout the 1950s, but in 1964 Vincent Dole and Marie Nyswander conducted a pilot study on outpatient methadone maintenance therapy at the Rockefeller Institute. 11 Despite considerable opposition from the Federal Bureau of Narcotics, oral methadone substitution programmes became increasingly popular. Government support for opioid substitution programmes grew as further public health benefits became apparent. In the 1970s, the US government found oral methadone substitution therapy to be effective in the treatment of heroin-addicted Vietnam veterans, and later it proved useful in preventing the rapid transmission of HIV in intravenous drug addicts. 7
Buprenorphine, a drug with opioid agonist and antagonist properties, was discovered in 1966 by researchers at Reckitt & Colman in Hull, England, where they had been developing new synthetic opioids. Reckitts supplied buprenorphine to Lexington throughout the 1970s for addiction research. As there was growing opposition to the use of prisoners for research, a group of ‘healthy male federal prisoner volunteers’ was required to give informed consent before entering into the buprenorphine trials. 12 Although former addicts, ‘none were tolerant or physically dependant on narcotics’ at the time. The researchers concluded that buprenorphine had obvious therapeutic application as a maintenance drug in narcotic addiction due to its long duration of action and low addiction potential. This was one of the last trials conducted at Lexington as research involving prisoners was finally prohibited in 1979. Buprenorphine was subsequently approved for addiction treatment by the US Food and Drug Administration. 4 Reckitts released a sublingual form of buprenorphine in 1982, and by 1985 injectable buprenorphine had been approved in 29 countries, with the sublingual form available in 16 of those.
Sublingual buprenorphine and oral methadone are now widely used in the treatment of drug addiction and have found a place in chronic cancer and non-cancer pain. These drugs are not without problems in this context: although methadone only accounts for approximately 2% of prescribed opioids in the US, in 2009 it was estimated that 30% of the 15,500 US deaths from prescription analgesics were due to methadone. 8
In Australia, on a particular day in 2017, almost 50,000 people were on a pharmaceutical regimen for their opioid dependence. Of those, 60% were on methadone, 25% on buprenorphine–naloxone and 15% on buprenorphine. 13