Methadone is a depressant, or "downer," drug prescribed primarily as a pain reliever for extreme pain that does not respond to non-narcotic treatment or as a treatment of heroin addiction and other kinds of opioid addictions. It has been used to treat heroin addiction for more than 30 years and is a cheap and safe alternative to opioid designer, or "street," drugs when correctly prescribed by a physician. Methadone stimulates one of the brain's opioid, or endorphin, receptors and blocks the receptor for the brain's main neurotransmitter involved in neuron excitement.
Pain Relief
Because methadone is a strong, effective analgesic or pain reliever, it particularly suitable for relief of intense pain, such as cancer and AIDS pain. Like heroin, methadone regulates pain by binding to the mu-opioid receptor. In natural circumstances, endorphins, the body's own pain-relievers that are released during extreme exercise, injury and trauma, bind to opioid receptors. Opioid drugs such as opium, heroin, morphine, codeine and methadone are able to bind to these receptors because they are akin to endorphins chemically.
According to a review published in the September/October 2003 issue of "Journal of Supportive Oncology," methadone also increases the brain's levels of serotonin and norepineprine by inhibiting reuptake of these neurotransmitters. Increasing the brain's levels of these neurotransmitters is known to have anti-psychotic and chronic pain-relieving effects.
Glutamate Regulation
Methadone also inhibits the NMDA glutamate receptor, which the excitatory neurotransmitter glutamate normally binds to. Whereas extreme concentrations of glutamate cause neurons to die from hyperactivity, normal levels are crucial to memory and learning. Perhaps for this reason, tolerance to methadone could lead to cognitive problems, reports a research team in the March 2007 issue of "Psychopharmacology." According to a report from the 2008 meeting of the International Society for Magnetic Resonance in Medicine, methadone's binding to the glutamate receptor may be partially responsible for increasing heroin cravings in heroin addicts in methadone therapy. The researchers found that with higher doses of methadone, glutamate blood concentrations decrease and heroin cravings increase. The most plausible explanation of this is that with less neuron excitation, the longing for an acute rush is felt more strongly. The glutamate-blocking effect of methadone may also explain why methadone lessens the euphoric effect of opioid drugs, the researchers report.
Histamine Release
According to a study published in the June 2004 issue of "Anesthesia & Analgesia," methadone, like heroin, has a potential for triggering the release of histamine in the central nervous system. Histamine gives rise to an inflammatory response, which can involve flushing, sweating, itching, watery eyes, nasal congestion and constrictions of airways. There are no hard data on why heroin causes a "rush," whereas methadone normally does not. It could be the difference in how the drugs are typically administered--intravenously versus orally. However, as reported in "Opiate Receptors and Antagonists: From Bench to Clinic," the large, sudden histamine release associated with heroin injections but more rarely with methadone intake can itself give rise to a rush, which could be another reason for the difference in the subjective experience of the two drugs.
References
- "The Journal of Supportive Oncology"; Prescribing Methadone, A Unique Analgesic; Paolo L. Manfredi and Raymond W. Houde; September/October 2003
- "Psychopharmacology"; Chronic Methadone Treatment and Repeated Withdrawal Impair Cognition and Increase the Expression of Apoptosis-Related Proteins in Mouse Brain; Mónica Tramullas, et al.; March 2007
- Diagnostic Imaging: Report from ISMRM: MRS Glutamate Measures Reflect Heroin Craving
- "Anesthesia & Analgesia"; Methadone for the Induction of Anesthesia: Plasma Histamine Concentration, Arterial Blood Pressure, and Heart Rate; Bowdle, et al.; June 2004
- "Opiate Receptors and Antagonists: From Bench to Clinic"; Reginald L. Dean, et al.; 2009
