Methadone for cancer (no) and cancer pain (yes)

Most people know of methadone as a long-term substitution therapy for people addicted to heroin, morphine, or other similar drugs called opiates or opioids. A good, free full-text description of methadone maintenance therapy (MMT) can be found in the 15 June 2001 issue of American Family Physician.

Now, in the 1 August 2008 issue of Cancer Research, Claudia Friesen and colleagues at the University of Ulm report that methadone can kill leukemia cells in culture and reverse acquired resistance to other drugs like doxorubicin (Adriamycin). Press reports to this effect appeared at the beginning of the month in ScienceDaily and Scientific American online.

However, Karl Schwartz of Patients Against Lymphoma and Lymphomation.org dialed us up for comment on the most complete description of this paper that appeared in ScienceNOW Daily News in an article by Rachel Zelkowitz entitled, "Relief from Rehab?"

Karl wrote primarily because a contributor to one of his patient discussion boards said that methadone would never be developed as a cancer drug because:

Methadone joins a long list of molecules that have shown activity in the lab but will never see the light of day as drugs as either they were not patentable in the first place (naturally occuring molecules) or their patient has expired.

Here was my response to Karl to pass along to his commenter:

1. Methadone is not a natural product although it binds opiate receptors - it is a synthetic diphenyl compound developed by the Nazis in WWII because of fears that opium extract (the source of morphine and codeine) would be subject to Allied blockade of supply routes, presumably from SE Asia. (Its discovery makes for a fascinating history lesson for another day, in part because it was the first drug that worked like morphine but didn't look like morphine structurally - plus Tom Cruise and the Church of Scientology still contends that its original brand name, Dolophine, was coined out of admiration for Adolf Hitler - in truth, it likely comes from the Latin word dolor meaning "pain" and fin meaning "end.").

2. Regardless of whether methadone is natural, natural products are indeed patentable but, as the writer notes, use patents are weaker. However, there are some cases where strong patents can be used to protect natural products. Taxol (paclitaxel) is a great example: one could not extract enough taxol from Pacific yew trees without sending them (and a species of spotted owl) into extinction. Bob Holton at Florida State came up with a 5-step synthesis beginning with 10-DAB, a chemical precursor derived from European yew needles (a renewable resource). Bristol-Myers Squibb licensed Holton's patented synthesis for their manufacture of Taxol and Dr, Holton is now a very wealthy man.

3. I would pay very close attention to the final statement in the ScienceNOW article from Dr Scott Kaufmann from Mayo Clinic - Scott is a MD/PhD who treats cancer patients and has his own basic science laboratory. But you don't need Dr Kaufmann's level of brilliance and accomplishment to understand a very simple concept: Many, many compounds kill all kinds of cancer cells in flasks (i.e., cell culture) yet few people (and some medical writers) consider that the concentrations of drug required to do so are either unable to be achieved in patients and/or are so high as to be even more toxic than conventional chemotherapy. Hence, Dr Kaufmann's point is that the concentrations of methadone required to kill leukemia cells are so, so high that the patient would be dead from a major side effect of opiate drugs: respiratory depression (i.e., the patient's breathing center in the brainstem would be depressed such that one would stop breathing).

On the other hand, I find it biologically tantalizing and curious that many cancer cells express various opiate receptors on their surface. Hence, I would not completely discount the importance of the work by Friesen and colleagues - although I did in the title of this post, I did so more to relay to cancer patients via search engines that methadone is not going to be a cancer treatment today or worse that patients may try to take extremely high doses of methadone that could be hazardous.

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Friesen, C., Roscher, M., Alt, A., Miltner, E. (2008). Methadone, Commonly Used as Maintenance Medication for Outpatient Treatment of Opioid Dependence, Kills Leukemia Cells and Overcomes Chemoresistance. Cancer Research, 68(15), 6059-6064. DOI: 10.1158/0008-5472.CAN-08-1227