Frequently Asked Questions

Do you want information about DON'T, ARM, or both? You can read about DON'T on the home page of the Methadone Today newsletter. DONT is the Michigan advocacy group for methadone patients, and ARM is a national methadone advocacy organization. Both organizations are 501(c)3 non-profits.

Both organizations have newsletters. DONT's publication is Methadone Today, a local newsletter which has been published since August 1995. It is a four-page monthly publication whereas ARM's newsletter is a national 12-page quarterly publication. The first issue was Fall 1999.
Both organizations also work to dispel the myths and end the stigma attached to methadone. We educate patients, clinic staff, the medical profession and general public. No, methadone does not get into your bones or rot your teeth. Methadone is the most studied drug, and over 30 years of study has shown it to be safe and nontoxic.

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What can you tell me about buprenorphine?

There is a new medication called buprenorphine (Subutex, Suboxone) that can be prescribed by doctors who have taken the proper training, but it may be difficult for some patients to switch from methadone to this medication. You should reduce your dose to 30 mg or less in order to switch over, or you could be thrown into withdrawal. If you are doing okay on 60 mg of methadone, you would probably do fine on buprenorphine. Anyone who needs more than 60 mg of methadone may not do well on buprenorphine.

Buprenorphine is more expensive than methadone because the pharmaceutical company still owns the patent; there is no generic drug yet. Your insurance company may pay for the prescription, but you may want to check this out prior to switching.

If you want to check into this, you should go to http://www.SAMHSA.gov Click on Addiction Treatment, then click on Office Based Treatment Now Available, and finally, click on Physician Locator.

What are methadone patients to do when drug testing is required for a job?

Methadone does not show up as an opiate, one of the things for which companies test. If they want to find out if you are taking methadone, they must check specifically for it. Not all companies do.

If they do check for it and don't hire you simply because you are taking methadone, then you have a case. Methadone patients are covered under the Americans with Disabilities Act (ADA), and you can file a grievance with the Justice Department.

If you don't get hired because you are taking methadone, you should try to get it in writing. If you can't, that doesn't mean you shouldn't still file against the company. Drug testing is usually the last step in the hiring process, so it is usually quite apparent what the deal is.

I'm pregnant, and I was told that I would have to get off methadone because it would hurt the baby. I have tried, but I can't seem to detox. Do you have any suggestions?

Do not berate yourself for taking this medication. That is what it is--a medication for a chronic, relapsing disease. Scientific studies have shown that pregnant, opiate-using women should immediately begin methadone maintenance treatment instead of risking relapse to heroin or other short-acting opiates. Heroin withdrawal is harmful, but methadone improves the chances for the unborn fetus.

Call the NIDA clearinghouse and ask for TIP 5, "Improving Treatment for Drug-Exposed Infants." It tells pregnant women to run, don't walk, to your nearest methadone maintenance program and get on methadone. It improves the chances for a healthy baby as opposed to remaining on short-acting opiates. This book is free for the asking. Call (800) SAY NOTO and ask for an information specialist. Then ask them for the above-mentioned book.
The TIP and TAP books are not simply one person's opinion. It is a consensus of experts in the field. You would do well to start with these TIP books.

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Can you direct me to research about the risks of breast feeding when on low doses of methadone?

I recommend TIP 2 from the Department of Health and Human Services for "Pregnant, Substance-Using Women" and TIP 5 also from the DHHS, "Improving Treatment for Drug-Exposed Infants." These can be obtained free of charge by calling (800) SAY NOTO and simply asking for TIP 2 and TIP 5.
Actually, there are no risks to the infant when breast feeding while taking methadone, period. It is not contraindicated but is encouraged. In fact, the small amount of methadone that may be in the breast milk should help if the infant is born dependent on the medication. It should help ease withdrawal in that case.

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I want to get off methadone. What is the best way to do it?

If you really must withdraw from methadone, it is best to do so very slowly. You should not withdraw from more than 10% of your dose per week at doses over 100 mg. That is, if you are on 150 mg, you could probably safely lower your dose to 135 mg. Once you get down to doses under 100 mg, you probably won't want to drop more than 2 mg per week until you get down to 50 mg. Then I would say you should drop only 1 mg per week or 2 mg every other week. Of course, not everyone is the same, and some people can drop more quickly. Others might not be able to drop this fast.

And by all means, if you put yourself on a schedule but find that you don't feel well, stop dropping and stabilize until you feel better. You may even want to go up a few milligrams until your body adjusts. Don't decide that you want to be completely off methadone by the next season coming up because your body might not listen to you. It might tell you that you shouldn't be completely off until next year--or the year after.

Before you even attempt to withdraw, ask yourself why you want to do so. If it is because your counselor or your parents or your significant other wants you to, forget it. You won't be successful. You must be the one who wants it, and you need to have all your affairs in order. That means you need to be working or doing something that you like to do, your finances should be in order, and you shouldn't have any issues you haven't dealt with. If you are ill or under stress, you absolutely do not want to try to withdraw at this time.

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I've gained a lot of weight on methadone; I sweat a lot, and I get constipated. Is this common?

Many people gain weight when they quit using drugs. There is nothing to suggest that methadone "causes" the weight gain. It is more likely the change in behavior when you quit using. Let's face it--using opiates is usually a full-time job. We have to find the money, then we run around trying to get the drugs. We don't eat right, and we would rather use our money for drugs than food. Once we get on methadone, we have a lot of time on our hands that we didn't have before.
For some people, one of the side effects of methadone is profuse sweating. I have had patients tell me that the kind of methadone they take reduces sweating (i.e., wafer vs. cherry liquid methadose), and others have said that lowering their dose a little has helped.

Constipation is another side effect. However, it usually goes away with time.

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I go to a clinic that is considered low dosage. I am now on 80 mg. The last time I asked my counselor for a raise, she said, "You are on a terribly high dose right now. She also recommended that when I have take homes to try drinking half my dose in the morning and the other half later in the evening. Well, later at the end of the week, I asked her if I get a raise, and she said I did. When I needed a document for work, it said that I was on 80 mg., so I was apparently lied to. I still feel really bad. I had a physical to see if I had Hepatitis; my counselor said I had symptoms. Any ideas?

The sad fact is that many counselors and many doctors do not have a clue when it comes to methadone. Your dose is not high; in fact, it is at the lower end of the effective range, and it sounds like you need a raise immediately. See the following articles: When Enough is Not Enough and Optimizing Response to Methadone Maintenance Treatment: Use of Higher Dose Methadone.

Why did your counselor have you split your dose? Are you sleepy or nodding if you take it all at once? Are you a fast metabolizer? If not, there is absolutely no sense in taking a split dose when what you need is an increase. If you are not showing signs of toxicity, you should be given an increase immediately and without question.

You might want to ask them to take a serum level to find out how many ng/ml of methadone is in your blood. If your trough is lower than 400 ng/ml, you need an increase. The problem with these serum levels, however, is that some of the clinics will use it against the patient. Methadone has an active and inactive metabolite, and a serum level does not distinguish between the two. Therefore, this test can make it seem as though you are on an adequate dose when you really are not.
Check out what I am talking about at:

http://www.methadonetoday.org/v2_n7.htm#Dose
You mention that your counselor said you have symptoms of Hepatitis. On what does she base this? Hepatitis may cause your dose to not hold you. I would insist upon a dose increase. Presently, it is felt that between 80 and 120 is an effective dose, but some patients need over 200 mg per day, and they are not overdosed. One patient is on 2,000 mg (yes, two thousand) per day. This person is a professional, and he is not overdosed. We need to get rid of this lingo "high dose" and "low dose" and start talking about individualized, effective doses.

Is there any chance you could go to a different clinic where they will dose you properly? Methadone is a great medication when it is used properly, and there is just absolutely no sense in you being miserable when a dose increase may turn things around.
Your counselor and doctor may "really" think that 80 mg is a high dose, and they may "really" be concerned about overdosing you. If this is the case, they need to become educated about the pharmacology of methadone.

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My significant other is a "patient" in a methadone clinic. It has been two or three weeks since he went up in dose, and his counselor is already talking detox! This drug is cheaper and cleaner than heroin. He has no intention of detoxing at this time, but how much "counseling" must one get?

I don't mind getting the earful, but it really angers me when counselors talk about withdrawing when the patient is apparently not ready. When I get a counselor, I tell them in no uncertain terms that I am on methadone as a maintenance medication and that I refuse to discuss withdrawal with them. I am staying on this medication and that's all there is to it. Now, if they want to waste their time and my time, they can continue beating their head against the wall, but I am not listening. I tried to withdraw several times, but I was not successful.
I have read every paper that I can get my hands on regarding methadone, and the reality is that most of us will either be on methadone for the rest of our lives OR we will be using short-acting opiates. Nobody "wants" to be on methadone for the rest of their life, but eighty to ninety percent of those patients who withdraw from methadone will relapse to short-acting opiates within two years.

I would like to know what counselors think they are accomplishing if they DO get a patient to withdraw from methadone. Trying to talk a patient into withdrawal is not counseling. Counseling is "listening" to the patient's concerns, supporting them and helping them reach their goals instead of trying to talk them into something they don't want.

Just because you are not a methadone patient, that doesn't preclude you from writing to Watchdog and filling out a clinic report. This program of needs to be in the doghouse; they are famous for trying to get patients to withdraw from this medication. Your significant other is not the only one who goes through this at the clinic of which you speak. This clinic IS a maintenance program! But there are certain counselors who continue to impose their values and wishes on the patients. Write to Watchdog and put it on the record that this clinic hassles patients to withdraw from this life-saving medication.

Tell your significant other to ignore the counselor who is telling him that it is not a maintenance program OR ask for a different counselor. Tell him to ask for one who understands methadone and who won't keep bugging your significant other to withdraw from his medication.

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What is your opinion about the hospitals that you go to where they put you to sleep, and when you wake up, you are cured; any truth to that?

The "treatment" you are talking about is called UROD (Ultra Rapid Opiate Detox). It is dangerous, and it doesn't work to cure addiction. Several people have died after UROD, and almost no one has remained free of opiates once the naltrexone implant is depleted. Some patients who have had this done have not even lasted until the naltrexone is gone. There have been reports of patients being so horribly ill from this that they have actually dug the implant out from underneath their skin. I urge you to forget about this.

You may be interested in the following article as to why patients keep returning to active addiction. This is why patients should stay on methadone:

http://www.methadonetoday.org/v4_n05.htm#withdrawn
http://www.methadonetoday.org/v4_n05.htm#Disorder

If you want to read reports from people who have contacted Methadone Today after having UROD or RAAD done, there are many stories in the back issues of the newsletter. Following is an article I wrote and examples of what you will find people saying who have gone through this:

http://www.methadonetoday.org/v2n1.htm#Naltrexone
http://www.methadonetoday.org/v3_n03.htm#Cure

http://www.methadonetoday.org/v3_n07.htm#Rapid-Detox

http://www.methadonetoday.org/doctip3.htm#Naltrexone-Related

http://www.methadonetoday.org/v4_n11.htm#Hype

http://www.methadonetoday.org/v4_n11.htm#Hell

Of all those who have contacted me after having this procedure, only one said it was a positive experience. However, I have my doubts about this person since he was solicited by a doctor who does this procedure to call and give me a good report. All unsolicited reports have pleaded with me to let people know that it is a horrible experience.

I know I've given you a lot of stories to read, but they are relatively short, and I hope you will take the time to read them. It took me some time to locate them, so please give it a shot.

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I will be working with a man who is on methadone, and I wanted to know if there is anything about the drug or people who are on it that I should be aware of. Does it make them irritable, angry, confused, etc.?

No, it will seldom make a patient irritable, angry or confused. On the contrary, it is great as an anti-depressant. And, unlike short-acting opiates, it boosts the immune system. Often doctors will refuse to treat an AIDS patient if s/he is on methadone. Many doctors are unfortunately ignorant of the fact that methadone, a long-acting opiate, is unlike short-acting opiates in that area (short-acting opiates depress the immune system). AIDS patients in particular should remain on methadone.

Methadone may make the patient sleepy, but once stabilized, there is no difference between a person on methadone and a "normal" person. Studies have shown that stabilized methadone patients can operate machinery, drive a car, etc. with no impairment. Most opiate addicts have a dysfunctional opiate receptor ligand system, and methadone normalizes it. That brings us to your next question.

How long are patients usually on methadone?

Another area where methadone is misunderstood is the length of time a patient should be on it. It's just like insulin for the diabetic. Insulin controls diabetes--while the patient is taking it. Blood pressure medication controls hypertension--while the patient is taking it. Methadone controls the disease of opiate addiction--while the patient is taking it. Even the most well-adjusted, committed person should think long and seriously about withdrawing from this medication (80-90% relapse to daily opiate use within two years--most relapse much sooner). The odds are against us when we quit taking it.

I'd like to insert some comments from an interview from Dr. Vincent Dole, the father of methadone maintenance treatment. If you wish to read the whole interview, see:

http://www.methadonetoday.org/v3_n02.htm#Dr. Vincent Dole
http://www.methadonetoday.org/v3_n03.htm#Part II

Also see: http://www.methadonetoday.org/v4_n05.htm#withdrawn

Odus: Should counselors start a patient's treatment with the goal of eventually being totally drug free, including free of methadone?

Dr. Dole: I think that has been a very serious misunderstanding from the beginning. The goal is NOT abstinence; the goal is to become functional. The data collected over the years has shown that abstinence is an unlikely goal. It is a terrible mistake to put someone in the position of either eventually becoming abstinent or becoming a failure. I am very sorry to hear that many clinics continue to do just that. Unfortunately, that is a philosophy at many clinics. They are willing to "put up with" maintenance in the short term, but they feel that a patient isn't really "cured" unless they are abstinent.

Odus: Do you see any similarities between your model and the clinics that exist today?

Dr. Dole: Well, of course I see similarities, but the main difference is the philosophy, which has been drummed into them by those who are anti maintenance, that the patient isn't "cured" unless they are "drug free", no matter what else. The patient can be employed gainfully, taking care of his family, and in all respects a fine citizen; still they feel that unless he is free of methadone, he isn't "cured". That is totally opposite from what I believed then and still believe today.

Odus: What percentage of your patients were eventually able to live completely free of all drugs, including methadone?

Dr. Dole: You see, even you are prejudiced to a degree, you want to know how many people get off methadone altogether when the question should have been, "How many patients were able to achieve a normal life consistent with their own abilities, strengths and so forth." The answer to that question is, "quite a large percentage were able to go on with their lives with some people reaching very high social and employment positions."

There is such a misunderstanding about methadone as a maintenance medication. I was in treatment for the first six years not understanding its pharmacology or the way it should be used. I would try to withdraw from the medication every time a counselor would bring it up, "You're doing so well. It's about time you 'get off this stuff'." Of course I was doing well. My addiction was being controlled, but it no longer was when I starting getting "off this stuff."

As Dr. Dole mentioned in his interview for Methadone Today, for the most part those in the clinic system "put up with" methadone as an interim treatment. The whole point to the clinic system is counseling, and counseling is supposed to prepare the patient for abstinence. Granted, the majority of methadone patients have dual diagnoses. Counseling will help that. However, part of the problem is physical, and no amount of counseling is going to change that.

When I started reading everything I could get my hands on about methadone and finally understood that I am not a weak person or a moral degenerate, I decided that I will probably be on this medication for the rest of my life. I no longer feel bad about it. Why should I? I don't get high off methadone; I get normal.

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Is methadone used for heroin withdrawal?

Although it is used for withdrawal, it isn't its main use. Opiate addicts have withdrawn many, many times. Withdrawal isn't the problem. Staying off opiates is the problem. Methadone's main purpose is to replace the endorphins that opiate addicts' dysfunctional opiate receptor ligand system no longer manufactures (or manufactures to a lesser degree than the "average" person). Methadone is mainly used as a maintenance medication, and it is used to maintain those who have taken too many short-acting prescription opiates also.

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Is methadone used as a painkiller?

Yes, it is. In fact, it is a very good painkiller. It is usually used at much lower doses as a painkiller than for maintenance for opiate addiction.

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I want to get a clinic started in my close-minded town. I am going to start a petition to open a methadone clinic here. Is there any advice you can give me as I start this task? I will be approaching the City Council and the County Board of Supervisors. It is a very backwards little town with small-town minds and views and this will be really tough. I need info on how to go about and do this correctly, can you steer me in the right direction ?

What I would do is have a firm grasp on all your facts and present them to one of the City Council or Supervisors on the Board at first. It is much easier to get one person to listen to you and give them the information than it is to try to convince everyone. Once you have the one person on your side, you can use him or her to help you convince the others.

You need to tell them that most likely what they have heard about methadone is not true. For example, it will not bring crime to their town. On the contrary, it reduces crime. It increases employment for the addicted, and it reduces heroin use. I don't have the percentages off the top of my head, but you need to have these statistics before you go to the first Supervisor. Be sure you have everything down pat before you talk to anyone.

Know your material like the back of your hand, and let them know where they can find information about methadone from the experts. You should order the TIP/TAP series from the Department of Health and Human Services. You can do that by calling (800) SAY NOTO and asking the information specialist for the TIP/TAP series.* It doesn't cost you anything, so I would order a set for you, and after you look them over, go through and order some of the more relevant books for them.

*TIP 43 is now available. It has combined several different TIPs, all regarding Medication Assisted Treatment, so you may only wish to order this TIP instead of the series.

There is also a great collection of articles regarding methadone that you can download from the internet. It is called "Methadone Treatment Works." There is a link to it from my site. Go to the Methadone Today home page in the blue bulleted area and click on the link .

Don't forget to tell them that our former Drug Csar, Barry McCaffrey has said there needs to be more methadone made available to addicts. The Institute of Medicine, the National Institute on Drug Abuse, the American Medical Association, and many other prestigious organizations have said that methadone is the best treatment for opiate addiction to date.

I'm sure you will be able to think of more things to do, but this will get you started.

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What can you tell me about serum levels?

American methadone is a 50/50 mixture of active and inactive forms. Swiss sometimes use pure form that has only active methadone, as well as the mixed (racemic) product used for maintenance in the US. These are called different names in different languages but are named for the right-handed or left-handed nature of the way the molecule transmits light. What is important is that only one of these methadone forms is biologically active. Our traditional serum level lab tests are based on adding the total methadone, both right- and left-handed. Combined values, which equal 450 ng/ml or greater, are cited as
being the minimum necessary for good treatment and abolishing craving.

The problem is that some patients metabolize methadone in a way that allows the 50/50 ratio of inactive/active methadone to vary widely. Some Patients can have far too little of active methadone, described in the article below as "R" methadone, but still have serum levels in the normal range. Others can be comfortable with low serum methadone test results because they have larger than average "R" methadone fractions in their system. In patients whose active/inactive (R/S, in the article below) methadone ratio is is less than .67 (=40 percent active methadone), Swiss clinicians (JJD) have observed signs and symptoms of withdrawal and emergence of craving, although their total methadone serum level would appear to be adequate.

In the US we need to medicate patients based on clinical signs and symptoms more than on serum levels. Tests which measure the two isomers are now expensive, and our literature does not yet reflect broad clinical experience with their use. Pure "active" methadone, which is usually dosed at fifty percent of the dose of our methadone is unavailable here (and costly, if it were).

Also see: doctip3.htm#Serum

v2_n7.htm#Dose

An article (abstract) follows:

European Journal of Clinical Pharmacology, Volume 50 Issue 5 (1996), pp 385-389.

Replacement of (R)-methadone by a double dose of (R, S)-methadone in addicts: interindividual variability of the (R)/(S) ratios and evidence of adaptive changes in methadone pharmacokinetics.

C.B. Eap , T. Finkbeiner , M. Gastpar, N.Scherbau, K. Powell , P. Baumann, Unit de Biochimie et Psychopharmacologie Clinique, Dpartement Universitaire de Psychiatrie Adulte, H pital de Cery, CH-1008 Prilly-Lausanne, Switzerland Rheinische Land- und Hochschulklinik Essen, Postfach 103043, cD-45030 Essen, Germany.

Abstract

Methods:

Twenty-two patients receiving (R)-methadone maintenance treatment were switched to a double dose of R,S)-methadone: blood samples were collected before and after the change, and the concentrations of the enantiomers were measured.

In the second period, during racemic methadone treatment, important interindividual variability in the stereoselective disposition of the enantiomers of methadone was measured, with (R)/(S) ratios ranging from 0.63 to 2.40. This point should be taken into account particularly with respect to therapeutic drug monitoring of racemic methadone.

Results:

A significant decrease, P < 0.005 in the mean serum concentration/dose ratios of the active (R)-enantiomer before and after the change, was measured (mean 3.97 and 3.33).

Conclusion:

Although of small amplitude (16%), this decrease confirms previously described adaptive changes in methadone pharmacokinetics during racemic methadone maintenance treatment and may necessitate, in some patients, a dose adjustment.

ISSN: 0031-6970 (printed version)
ISSN: 1432-1041 (electronic version)

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Immune functioning and methadone

Many physicians or medical professionals incorrectly believe that methadone inhibits the immune system and functioning. While this is true of all opioids and especially the short acting opiates, it is not true of methadone. And in fact, methadone is the only opioid that does not inhibit the immune system or functioning. This is an important characteristic of methadone when considering its impact on HIV+ methadone patients. But methadone does not only not inhibit the immune system--it restores immune functioning.

The potential for normalization of endocrine and immune functioning is especially crucial when treating HIV positive methadone patients. The evidence of immune restoration from HIV negative methadone patients hints that there may be a partial restoration of immune functioning for HIV positive methadone patients (Kreek, 1988). While this is not proven, there are many other advantages for HIV positive heroin users to be placed and maintained on methadone.
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In Switzerland a three-year prospective study followed a group of HIV-infected methadone maintenance patients and a contrast group of HIV-infected heroin users who did not enter methadone maintenance treatment (Weber, Ledergerber, Opravil & Luthy, 1990). The results showed that a significantly lower proportion of methadone maintenance patients progressed to AIDS as compared with the untreated heroin users, 24 percent versus 41 percent, almost a two-fold increase within the period of the study.

Methadone when prescribed as a maintenance medication functions as a normalizer for a deranged physiology and not as a mood altering narcotic substitute (Dole, Nyswander & Kreek, 1966; Joseph & Dole, 1970). Methadone maintenance is therefore corrective but not curative.
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Illicit Heroin Use and Immune Function

The continued use of heroin impacts negatively on the health of the user in many ways. Certainly, a primary effect is the unstable life of the heroin addict who does not eat properly or sleep normal. However, it must be emphasized that even the piercing of thet on the immune system. Injecting pills is no better because they contain buffers to hold the pill together and dies to color th skin, as during injection will effect the immune system. In addition the act of injecting illicit drugs are dirty and will adversely impace pill--neither should be injected. Only sterile water should be used which can be purchased in a large drug store or medical supply store. Tap water contains bacteria which will also impact on the immune system and boiling water for short periods will not completely sterilize the water. If you cannot get sterile water then you could use distilled water which can be purchased at a drug store or boil tap water for a full 15 minutes. However, injecting will weaken the immune system and even if one only injects once in awhile each injection will begin to impact negatively on the immune system.
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The Potential Mandate of Methadone Programs on HIV Infection

Methadone programs are placed in a unique position to monitor HIV and other infectious diseases and provide clinical prevention and intervention. For example, AZT can be administered as well as medications for drug-resistant TB. Most importantly, clinics can offer AIDS prevention, counseling and referrals for services that exist in the community. Special methadone clinics and programs can be developed that serve patients infected with HIV (e.g., St. Claire's MMTP, Beth Israel AIDS program on 125th Street). Unfortunately, most programs do not have the funding to provide these services to their patients, and it is up to us to let our legislators know that these services are not only necessary in methadone programs, but it would be more efficacious to the health care system for methadone patients to be treated for conditions other than their addiction in methadone programs.

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References

Dole, V.P. Implications of methadone maintenance for theories of narcotic addiction. Journal of the American Medical Association 1988 (November 25) 260(20): 3025-3029.

Dole, V.P., Nyswander, M.E. and Kreek, M.J. Narcotic blockade. Archives of Internal Medicine 1966 (October) 118:304-309.

Himmelsbach, C. Clinical studies of morphine addictions. Nathan B. Eddy Memorial Award Lecture. In: Harris, L.S. (ed), Proceedings of the 49th Annual Scientific Meeting of the Committee on Problems of Drug Dependence. National Institute on Drug Abuse, Research Monograph Series 81. Rockville: U.S. Dept. of Health and Human Services, 1968.

Kreek, M.J. The addict as patient. In: Lowenson, J.H.; Ruiz, P.; Millman, R.B. and Langrod, J.G. (eds), Substance Abuse A Comprehensive Textbook. Baltimore: Williams and Wilkins, 1992.

Kreek, M.J. Summary of Presentation at 1988 meeting of the Committee for the problems of Drug Dependence. NIDA Notes 1988 Fall: 12, 25.

Kreek, M.J. Multiple drug abuse patterns and medical consequences. In: Meltzer, H.Y. (ed), Psychopharmacology: The Third Generation of Progress (Chapter 172), p 1597-1604. New York: Raven Press, 1987.
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Kreek, M.J. Tolerance and dependence: Implications for the pharmacological treatment of addiction. In: Harris, L.S. (ed), Problems of Drug Dependence. Proceedings o the 48th Scientific Meeting of the Committee of the Problems of Drug Dependence, 1986. DHHS No. (ADM)87-1508. Rockville, MD: National Institute on Drug Abuse.

Kreek, M.J. Medical complications in methadone patients. Annals of the New York Academy of Sciences 1978 311: 110-134.

Kreek, M.J. Medical safety and side effects of methadone in tolerant individuals. Journal of the American Medical Association 1973 (February 5) 223(6): 665-668.

Kreek, M.J.; Dodes, L.; Kane, S.; Knobler, J. and Martin, R. Long-term methadone maintenance therapy: Effects on liver function. Annals of Internal Medicine 1972 (October) 77(4): 598-602.

Hartel, D.; Selwyn, P.A.; Schoenbaum, E.E. et al. Methadone maintenance treatment and reduced risk of AIDS

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