Abstract
The research paper discusses the origin and nature of methadone, including the historical aspect of its development and further commercial and scientific use. The paper also describes the pharmacology of methadone, including the route of administration of the drug, its metabolism and its mechanism of action. Next section of the paper explains the experience in medical use of methadone, as it`s a great alternative to the painkillers based on the opiates, it plays a major role in the therapy of maintaining and replacement and treating the withdrawals syndromes. The positive effects on the pregnant patients are also described here with a further notation on the effects of methadone on driving abilities. The last section of the paper briefly describes the social reaction of the use of methadone and its criticism about it. The end of the paper summarizes the information mentioned in the previous section and comes up to a logical conclusion.
Methadone is a synthetic opioid that has a variety of different names, as Dolophine, Symoron, Methadose, Amidone, Heptadone and many others; it is used as an analgesic in medicine in supporting the reductive and anti-addictive treatment of patients that suffer from an opioid dependency. As it`s an acyclic analogue of heroin and morphine, it affects the same receptors similar to these drugs, therefore its effects are also of the similar nature. Methadone is also used as a powerful painkiller due to the long-lasting duration of its effects and their power to treat the severe chronic pain; moreover, it has a comparatively low cost.
As it was also mentioned before, it`s more often used to treat the narcotic dependence due to the tolerance to the drugs of the same origin (like morphine and heroin) and the durability of its effects. The lesser doses of methadone have an ability to balance the condition of patients suffering from opioid withdrawal syndrome, soften or make it less painful for them. Methadone`s high doses can even block the effects of heroin and other opiates, and their euphoric effects in particular. Theoretically, a properly dosed methadone treatment can shorten or even stop the further use of opioid narcotics; however, it obviously cannot reduce the negative effects of other drugs, like methamphetamine, it cannot be used to treat an alcohol addiction also.
There is a variety of pharmaceutical companies that produce and sell methadone in the form of racemic hydrochloride, as it can be found in the drug stores of US and countries of EU. The methadone`s dextrorotary enantiomer is found to be more an NMDA antagonist than an agonist of opiates; that`s why the medication of a narcotic addiction use only levomethadone (its levorotary enantiomer), also well known under the names of Heptadon and Polamidone, but it has a variety of different names also.
It was a great painkiller, indeed; however, it proved to be causing lethargy, apathy, depression, reducing the will of soldiers to return to the battlefield as a result. Therefore, it was rejected for military use until 11 September 1941, when chemists Ehrhart and Bockmühl applied to patent their synthetic matter under the name Polamidon (codename Hoechst 10820), which is still widely used in Germany. The substance had a slightly related structure to any opiate alkaloids and morphine, in particular.
After the Second World War, all the trademarks, research records and patents were expropriated and requisitioned by the Allied Forces; therefore, all the documentation with the researches by I.G. Farbenkonzern was expropriated also by the Department of Commerce Intelligence of the United States and after the investigation and checking by the US Department of State`s Technical Industrial Committee, all the results of the researches by IG Farben arrived to US.
Since then, it was found out to have the effects in healing the opiate addiction, as it proved to be a successful method of the treatment; however, its official use was only as an analgesic. After that, Professor Vincent Dole, accompanied by Mary Nyswander and Mary Jeanne Kreek from Rockefeller University in New York City conducted a study proving that methadone could be used as an effective option for a substitution therapy. The results of their research showed that drug addiction was not only a matter of psychology and the will of a person, they proved that addiction could be treated, as many other diseases. Since then, the methadone use proved to be the most successful and officially accepted, as a pharmacotherapy for drug addicts.
First manufactured in US by Eli Lilly and Company on 14 August 1947, as Dolophine in 5mg and 10mg tablets, and the company was one of the least to be approved for the official production of the drug. For example, Mallinckrodt Pharmaceuticals wasn`t approved by the officials to produce methadone; however, their branded Methadose 5mg and 10mg tablets were approved for production only on 15 April 1993. Eventually, they have got the approval of their 40mg Methadose tablets on 27 April 2004. To this day, methadone is produced by a variety of pharmaceutical companies through all over the world, as it was already mentioned above.
It also should be briefly mentioned about the pharmacological peculiarities of methadone. The route of administration of it is usually a racemic oral option despite the fact that only R enantiomer is traditionally used in Germany due to the fact that it possesses the majority of the most expected effects of opioids. However, this trend started to decline recently because of the expensiveness of the production.
Methadone is usually formed into a sublingual tablet that is supposed to be drank by the patient; however, there are also the drinkable forms of it like ready-to-dispense liquid and in a tabled to be dispersed in water for oral administration also. The liquid form is the most effective option when there is a need of a smaller dose of the substance. As for the injections of methadone, they are of approximately the same effectiveness as an oral administration; however, the injection of methadone pills can cause harmful effects like swelling, bruising and even can cause the collapse of veins; moreover, every pill of methadone contains a talc as an ingredient, therefore, with the injection it melts into a mass of tiny particles delivered into blood with the substance. These particles form a numerous number of microscopic blood clots and they are impossible to be filtered out before the injection, therefore, they will simply be accumulated in body eventually. They are usually accumulated in eyes and lungs and produce a variety of complications and diseases, which could be progressive and even irreversible. There have been a number of reported cardiac arrests and occasions of damaged veins due to the injections, therefore, experts highly recommend using an oral consumption of methadone instead of injections.
As for its mechanism of action, it binds to the µ-opioid receptor; however, it also has a proximity with NMDA ionotropic receptor of glutamine. Enzymes CYP2D6, CYP2B6 and CYP3A4 metabolize it and it is a substrate for the P-Glycoprotein in brain and bowels. The elimination half-life and the bioavailability of methadone varies individually and depends mainly on the route of destination. The adverse effects of methadone include miosis, constipation and hypoventilation; moreover, the discussed above effects of dependence, tolerance and withdrawal difficulties are common for it also. It also can be noticed in the samples of urine in six to ten weeks after the last medication despite the common meaning that it leaves the organism within 2-3 days after the last dose. Still, the human organism peculiarities like metabolism, weight and the history of previous medications affect the time when methadone leaves the organism completely.
As for the metabolism, Methadone`s is slow and it`s fat solubility is very high, that`s why it appears to have a longer durability among the other opiates. Just like the half-life elimination, the metabolism also varies from one patient to another, as its time may range from 4 hours up to 130 and sometimes even to 190 hours. This range is usually explained by the generic volatility of the production of associated enzymes CYP2D6, CYP2B6 and CYP3A4. Obviously, in case of a longer half-life, the patients consume one dose per day and even less while they are the participants of the detoxication and maintenance programs. On the other hand, the patients that quickly metabolize methadone can afford themselves two doses per day to avoid excessive troughs and peaks in the concentrations of their blood, obtaining an adequate alleviation of the symptoms.
Methadone is widely used as the part of detoxication and maintenance therapy, as it was mentioned above. The last one is considered to be the continuous administration of methadone to the patients addicted to the opiates; moreover, the procedure is also long-lasting. It`s main goal is to replace the illegal heroin that was administrated parenterally and has a high rates of mortality with legal methadone with high durability and the effects that can soften the symptoms of addiction. The therapy allows a person to free himself from the addiction and the life full of procurement and drug abuse and can transform a drug addict to a socially accepted person. As it was discussed before, methadone blocks the euphoric effects of opiates, prevents the withdrawal symptoms, therefore, it minimizes the addiction itself. The methadone maintenance therapy proved to be a remedy of the drug abuse massively, decreased the number of infectious diseases like hepatitis and HIV that were contracted through the sharing of the same syringe. It reduced mortality and criminal activity; it also improved the social outcome, as the result. Usually 5mg of heroin administrated parenterally are equal to the 20mg of methadone transmitted orally. However, due to the fact that the purity of heroin purchased from street drug dealers varies drastically, it is also recommended to dose the methadone empirically, taking into consideration the peculiarities of the patient`s organism. Therefore, the dosage of methadone for therapy remains uncertain, as traditionally it starts with 10-20mg of the substance increasing the dosage per 10mg until the full control of the withdrawal symptoms. The majority of patients can be treated with 40mg per day to soften the withdrawal symptoms; however, it cannot annihilate the drug addiction.
There are many documented and reported facts that the administration of methadone in higher doses improves the effectiveness of therapy despite the previous views on the treatment that used the lowest doses possible to restrain the symptoms of withdrawal. However, due to a popular concern of high risk of HIV instances among the persons that use the drugs intravenously, the effectiveness of methadone therapy can be more adequately measured by the occasions of illicit use of heroin during the therapy. The studies conducted by a variety of scholars and scientists proved that the drug addicts that were on the therapy and received at least 80-100mg of methadone per day instead of the ones that had twice less, were noticed to administrate heroin intravenously.
As for the second option of methadone medical use, it is called the methadone detoxification and it means the use of short-term methadone administrations to soften the abstention symptoms of former drug addicts with a continuous decline in the doses of methadone to attain the state of full sobriety. The main minus of this therapy is the large number of heroin relapse after the end of the therapy that is usually explained by the psychological factors and the consequences of the withdrawal syndrome that remains for a long time after the drug addiction. For the detoxification procedure, the dosage traditionally starts with 10-20mg of methadone and then increases per 10mg until the full control of withdrawal syndrome symptoms. As it was also discussed before, a dose of daily 40mg can control it; however, it can`t fully reduce the craving for heroin. At the moment, when the needed dose is established and the withdrawal syndrome is under control for 2-3 days, the dose starts to reduce daily. Traditionally 10-20% of daily shortage is successfully used, but the shortage percentage also depends on the peculiarities of the human body. If a practitioner notices the possibility of abstinence syndrome that can result in a heroin relapse, he usually considers the increase of the dose to put the syndrome under control again. After the procedure is completed, every patient is monitored for the abstinence syndrome symptoms after the end of drug administration, as these symptoms reveal themselves only after 48-72 hours after the last dose.
Methadone is widely used as an alternative to morphine sulfate in treating the chronic pain of high severity, as it is well disperses orally, has the qualities of other opiates in softening the pain and has a long durability, which was said a couple of times already. Despite the fact that methadone and morphine are of the same nature and have equally good analgesic effects, switching a patient from one drug to another should be performed with a high caution due to the unclear relation of doses between these drugs.
There also was an interesting research describing how the use of methadone affects the ability of patients to drive. It`s a well-known fact that the drug abusers are one of the cause of car crashes; however, a person that is prescribed methadone for oral administration only can prove his ability to drive before an independent medical commission and can have a driving license for a year while being on a treatment. The patients that are prescribed to have parenteral administration of methadone are forbidden to drive due to the highly sedative effects of this way of administration.
As for the social acceptance of the methadone usage in medical treatments of drug abuse, the experts are critical and cynical. They criticize the whole procedure, as they consider it to be not the way of treatment of drug addicts, but to control them on an official level. They explain it that officials give the legal drug to the drug addicts for a low price with less negative consequences; they claim that this policy is widely spread among the hospitals and rehabilitation centers; moreover, prisons are not an exception in this situation also. They simply claim that it`s the way of management and control the least desirable social classes. Nevertheless, these experts should accept the fact that they can always return to heroin that they know how to get and prepare for administration and that has the euphoric effects. Still, the claim of these experts needs deeper and better reasoning.
Summarizing everything that was mentioned above, it should be said that methadone is one of the most controversial inventions of the 20th century. On the one hand, it achieved its popularity in medicine as a strong and more legal alternative to all the other opiates in pain treatment and the therapies of replacement and maintaining the withdrawal syndromes of drug addicts; on the other, it`s still an addictive narcotic substance, administration of which should be precisely controlled and performed properly due to the variety of negative consequences on health and life of a person.
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