Methadone's chemical structure
The Methadone Myths…
Methadone was first synthesised in Germany in 1938 by chemists working for IG Farbenindustrie. There are several widely-circulated stories about the birth of methadone which are of doubtful veracity. It is often said, for example, that the new pharmaceutical was dubbed Dolophine in honour of Adolf Hitler. In fact, it was originally tagged with the unimaginative name of Hochst-10820 (Hochst being the name of the factory where it was invented), and later named Palamidon. Another widely-circulated story has it that the chemical was synthesised for use as an analgesic, eliminating Nazi Germany’s dependence on Turkish opium for morphine, or that it was created on the personal orders of Reich Marshal and Luftwaffe commander Hermann Goering, a heroin addict, to ensure that cold turkey could be kept at bay if supplies of morphine were cut off. Attractive as this last story is, and while it is true that Goering was a junkie, it is probably apocryphal.
Methadone was not brought into wide production during the war at all, and its properties were only studied later. After the war the Hochst factory fell into American hands and as a part of the wholesale plundering of German scientific and technical knowledge (which saw V2 rocket technology and Nazi advanced weapons and intelligence expertise appropriated by the US military-scientific establishment under Operation Paperclip) the methadone molecule too, ended up as loot of war.
More Than Morphine?
It was the American pharmaceutical company Eli-Lilly who began the first clinical trials in 1947 and it was here that it was first christened Dolophine, probably derived from “douleur” and “fin”, the French words for, respectively, “pain” and “end”. The chemical was found to have a similar pharmacological action to morphine, despite its very different chemical structure, and it was much longer-acting. Once these facts were established, methadone disappeared into obscurity in the USA for over a decade. While its chemical cousin pethidine – which, incidentally, was produced in bulk in Nazi Germany as a morphine substitute -and is still used today to ease women’s labour pains, methadone never really caught on as a narcotic analgesic in America.
The earliest accounts of methadone use in the UK are from 1947, when a paper published in the medical journal Lancet described it as “at least as powerful as morphine, and ten times more powerful than pethidine”.
By the end of 1968, the year when the Home Office notification/registration system of addicts was introduced, 297 people had been notified as being addicted to methadone. Doctors who thought it less addictive than other opiates had begun prescribing them the drug however, through the 1960s, patterns of drug use were changing; Opiate addiction, which had until then, primarily been an indulgence of the wealthy (or medical professionals themselves), was now being picked up by younger people, taking opiates for pleasure rather than for pain.
1968 also saw the introduction of drug treatment clinics and the abolition of free prescribing. The clinic system effectively removed the GP’s discretion in the prescribing of controlled drugs and specialist centres took over the treatment of the majority of dependent drug users, a practice that continues today. In the first years of the clinics, doctors freely prescribed pure pharmaceutical heroin and methadone in injectable form for addicts. The introduction in the mid 70s of smokable Middle Eastern brown heroin resulted in many users arriving for treatment not expecting to inject their drugs, encouraging the clinics to move towards using oral methadone for treatment.
Methadone Maintenance – The Minimum Vs the Maximum
Methadone maintenance treatment, as we recognise it now, was pioneered in the USA in the early 60s. In 1963, two New York doctors by the names of Marie Nyswander and Vincent Dole began exploring methadone as a possible treatment for opiate addiction. There was a screaming need for it – by the end of the decade, heroin-related mortality had become the leading cause of death in New York for young adults aged between 15 and 35. Dole and Nyswander identified the features of methadone that made it a suitable maintenance drug. At doses beginning at 80mg per day, it effectively blocks the euphoric effects of all opiate drugs. Patients stabilised on methadone do not experience euphoric effects and tolerance does not develop like many other opiates, necessitating ever-increasing doses. Tolerance to methadone’s pain-killing effects does develop however, meaning patients experience pain normally although trying to explain this to a nurse or doctor when you’re in A & E is another matter entirely. As it is a long-acting drug, it can be administered once a day, enabling a greater level of stabilisation as compared to shorter-acting opiates.
Nyswander and Dole operated on the premise that heroin addiction is in effect a metabolic disorder, comparable perhaps to diabetes. Large doses of methadone – 80 to 150mg – were used to normalise the disorder, as insulin is used for diabetes. They combined this theory of treatment with efforts at psychological counselling and social rehabilitation, including help and encouragement in finding work. Many of their patients benefited greatly from the treatment and were successfully re-integrated into “normal society”, such as it is. The use of the treatment spread, but was not necessarily implemented with the innovation displayed in the work of Nyswander and Dole. For example, more than half of the USA’s 120,000 methadone patients today are treated with dosages well below those recommended by their research.
To read the rest of this article and find out about methadone’s pros and cons and the trials of treatment, click here.