What is Methadone?

How agonists ease agony for heroin addicts.

It isn’t the best, the worst, or the only treatment for heroin addiction. But for many heroin addicts, it has been a way out of the circle of euphoria and dispair.

In contrast to antagonist drugs, the agonist theory is based on drugs that bind to specific sites and which mimic some of the addictive drug’s typical range of effects. For obvious reasons, this greatly reduces craving. But is it simply a replay of the historical tactic of substituting one addictive drug for another?

The most successful use of the agonist theory remains heroin’s most controversial and stigmatized treatment—methadone therapy. Back in the 1960s, researchers at Rockefeller Hospital and The Rockefeller Institute, led by Professor Vincent Dole of Rockefeller University, began a series of studies that led to the development of methadone treatment. They did it on the strength of their belief in the unfolding biological model. “Heroin addiction is a disease of the brain, with diverse physical and behavioral ramifications, and not simply due to criminal behavior, a personality disorder, or ‘weak will,’” wrote Dr. Kreek, one of the principle methadone researchers at Rockefeller.

Methadone was approved by the FDA in 1973 for medical use against heroin addiction. It is a slow-acting opiate receptor agonist, meaning that it has some of the properties of heroin and morphine. However, the buzz it provides is no real substitute for heroin or morphine, from an addict’s point of view. It was nobody’s idea of a sweet drug holiday. But why give agonist drugs to addicts at all? Isn’t that just like giving them watered-down heroin? Writing in the September 2002 issue of Nature Reviews Drug Discovery, Dr. Kreek summed up what doctors face when dealing with long-term addiction:

"Repeated ‘on-off’ exposure to a drug of abuse progressively leads to stable molecular and cellular changes in neurons, which alter the activity of neural networks that contain these neurons. This eventually results in complex physiological changes and related behaviors that characterize addiction, such as tolerance, sensitization, dependence, withdrawal, craving and stress-induced relapse. These drug-induced changes are, in part, counteradaptive, and they contribute to dysphoria and dysfunction, which promotes continued drug use through negative-reinforcement mechanisms."

Daily methadone doses of 80mg or more exert a definite blocking effect on heroin craving. And patients who use it do not suffer the same lassitude and intensity of cognitive distortions as the heroin addict. Methadone’s other strength is that it doesn’t mix well with heroin or alcohol. 

More recently, Kreek and her colleagues, in collaboration with the NIH, used PET scans to watch opioid-receptor binding occur in the living brains of methadone-maintained patients. The brain scans confirmed that methadone leaves a significant number of opioid receptors unoccupied, allowing those regions of the brain to carry out normal physiological roles.

“In methadone-maintained patients there is modest occupancy of the receptors but still a lot of available receptors for normal cognition, normal reproductive function and normal stress responsivity,” Kreek reported.

Another underreported advantage of methadone is its oral administration, thus eliminating the need for hypodermics and reducing the risk of AIDS and hepatitis from contaminated needles. Provided the dosage is right, patients can be maintained for years on methadone. One reason methadone therapy fails, say researchers, is because of inadequate dosages—but higher dosages are much harder to withdraw from.

Photo Credit: http://www.wilkeseastna.org/