Lesson 1: Brief History of Methadone Maintenance TreatmentA short introduction about how methadone started. The original team consisted of four and included Drs. Dole and Nyswander who were the investigators, Dr. Herman Joseph who did the statistics and Dr. Mary Jeanne Kreek who was a medical student at the time.
Lesson 3: The Discovery of Endorphins by Joycelyn WoodsA brief history of the discovery of opiate receptors and endorphins. It is interesting to note that the first research was undertaken in Dr. Dole's laboratory at Rockefeller. However at the time it was abandoned because the technology was not yet available and Dr. Dole was to busy with setting up methadone programs.
Methadone maintenance treatment came into being in an
unexpected way. By 1963, on the cusp of the social revolution of the
sixties, doctors and public health workers had concluded what objective
observers and users alike had known for decades: that there was no
treatment known which could cure more than a small fraction of long term
opiate (heroin, morphine, etc) addicts. In fact, there wasn't even any
treatment which could honestly claim to be more successful than no
treatment at all! Every imaginable option had been tried, from lobotomies
and insulin shock to psychoanalysis and the threat of lifetime
incarceration. But in every case the result was the same: between 70 and
90 percent of these chronic addicts would return to opiates within a short
time. In light of such statistics a number of prestigious panels examined
the problem and by 1963 had come to the same conclusion: it was time to
re-examine nearly fifty years of prohibition and consider allowing doctors
to prescribe addicts the opiates they needed.
At Rockefeller University in New York City, Dr. Vincent Dole, an
expert in metabolic disorders, and Dr. Marie
a psychiatrist who'd worked at the U.S. Public Health
Hospital/Prison for addicts in Lexington, Kentucky, began experiments with
several chronic heroin addicts. In attempting to determine if addicts
could be maintained on stable doses of pharmaceutical opiates, the
volunteers were given access to the spectrum of opiates available to
medical practitioners. The researchers tried everything from morphine to
dilaudid, but found that it was extremely difficult to stabilize the
subjects. The addicts were either oversedated or in mild withdrawal most
of the time, and spent their days either "on the nod", waiting for their
next shot, or comparing the relative merits of the drugs used.
Reluctantly, Drs Dole and Nyswander concluded that the experiment had been
a failure, and decided to "detox" the addicts and release them from the
hospital. To accomplish the withdrawal, they turned to a synthetic
narcotic called methadone. Methadone had first been synthesized by German
chemists before World War Two, and after the war it was used to withdraw
addicts at Lexington. It had the advantage of being cheap, significantly
orally active, and longer lasting than opiates like morphine. For the
researchers at Rockefeller, it seemed merely a convenient and humane means
of ending the experiment with maintenance. As the addict volunteers had
been built up to large doses of narcotics by street standards, they were
given relatively large doses of methadone to stabilize their "habits"
before beginning the reduction.
And then something completely unexpected happened. A few days after
the subjects had been switched to methadone, and before the "detox" had
begun, they began to exhibit very different behavior. Whereas for weeks
they had spent their days either feeling the effects of the narcotics or
complaining of their need for more narcotics, suddenly the focus of their
days turned away from drugs. One subject asked the researchers for
supplies so that he might resume his long neglected hobby of painting.
Another inquired after the possibility of continuing his interrupted
education. In short, the addicts- who when admitted to the hospital had
looked and behaved very much alike -now began to differentiate.
They began to manifest the potential that each had obscured during years
of chasing street narcotics.
Schaffer Drug Library (pdf format) You can download the entire book for free from the Scheffer Drug Library.
In the Course of Professional Medical Practice (pdf format) by Vincent P. Dole M.D.. NYS Journal of Medicine 1966 55(7): 927-930.
Note: This was the first paper publishede on methadone and it is an editorial spoofing the Harrison Narcotic Act. Dr. Dole was preparing to challenge the Bureau of Narcotics (now the DEA).
Narcotic Blockade (pdf format) byDole, V.P.; Nyswander, M.E.; and Kreek, M.J. Arch Intern Med 118:304, 1966.