Originally published 1/7/2015
We researched more recent information on the anti-opioid drug naltrexone to learn if more progress has been made since our original post below.
We found a 2016 study on the effects of low dose naltrexone on cancer cells (though not prostate cancer specific).
The authors found it had some ability to reduce tumor growth, modulate some immune system capacity, and increase the effectiveness of chemotherapy, concluding that it “possesses anticancer activity.”[i]
Of greater interest was a 2022 report of six prostate cancer cases treated with an immunotherapy called IMM-101 in combination with “the correction of vitamin D3 levels, and combination with other agents that have anti-inflammatory and immune-modulatory abilities, such as bromelain and low-dose naltrexone (LDN).”[ii]
The authors observed that the effect of IMM-101 was boosted when low dose naltrexone was used. PSA levels were reduced and in some cases MRI and PET scans showed the cancer had stabilized.
The authors note there were few side effects of combined treatment, and that “IMM-101 treatment alongside an anti-inflammatory agent, such as bromelain and/or LDN, may be considered an active and safe drug combination, and is a regimen that should be considered for treating patients with prostate cancer.”
Thus, low dose naltrexone provides some reason for optimism.
Because of my interest in immunotherapy, especially in conjunction with focal treatment of prostate cancer, I investigated claims that naltrexone (a drug approved for treatment of alcohol or opioid[1] dependency) can normalize the immune system when taken in subtherapeutic (low) doses. Naltrexone is an opioid receptor antagonist, meaning it blocks the effect of opioid drugs. However, laboratory studies and clinical observations suggest that giving low doses of naltrexone to animals and humans with tumor activity may enable the immune system to tackle a range of diseases, including cancer.
Naltrexone was developed in the 1960s when two researchers, Drs. Bloomberg and Dayton, were seeking a nonaddictive drug that could alleviate pain. Naltrexone did not fulfill their hopes, but the 1960s brought evidence that the drug helped manage addiction to opioids; a daily oral dose of 50mg blocks the sensation of a “high.” In the early 1980s, Dr. Ian Zagon and his team analyzed the effect of naltrexone on the body’s own endorphins, our natural pain and stress relievers. They found that giving a low dose of naltrexone before sleep produces a temporary period in which the brain’s opioid receptors are blocked, leaving the free-floating endorphins to be picked up by receptors in the immune system’s components such as T cells and bone marrow progenitor cells. In turn, this seems to up-regulate the immune system.
Zagon and others, reasoning that making endorphins more available could normalize immune activity in patients with endorphin deficiency, began to pursue two parallel lines of study:
- The effect of low dose naltrexone (LDN) on people with diseases caused by or related to low levels of natural endorphins (e.g. autoimmune diseases and some cancers)
- The effect of LDN on people whose shortage of natural endorphins accelerated a disease process (e.g. HIV/AIDS).
The list of diseases that improved with LDN grew. Claims about conditions ranging from bladder cancer, multiple sclerosis and psoriasis to the common cold were made. And yes, prostate cancer made the list. A number of pilot studies were initiated from the 1990s on to today. LDN websites promoted the merits of the drug. But are the claims well founded? Science writer Steven Novella, who calls the biologic science behind LDN fairly standard, addressed the question:
In the case of LDN the major problem comes at the level of translational research – taking what we are learning from basic science and applying it to specific clinical applications. It should be noted that this type of research is very unpredictable. Most of the promising leads provided by basic science do not lead to effective treatments. There are many possible reasons for such failure to translate to clinical outcomes. It is possible that the basic science picture is still significantly incomplete, and the piece or pieces that are missing alter the ultimate clinical effect of the intervention. It is also possible that the basic science is simply wrong in one or more of its conclusions. Further, the basic science may be correct, and the predicted outcome legitimate, but the size of the effect clinically insignificant, and therefore not seen in clinical trials.[iii]
Novella searched the PubMed data base and studied the promotional websites. He found a range of preliminary studies (see research levels at https://sperlingprostatecenter.com/foundation-medical-research/ ) on various medical conditions treated with LDN. He found the long list of cancers, autoimmune conditions and neurological problems suspicious, and took lowdosenaltrexone.org to task for making LDN sound like snake oil. Novella took his critique one step further by emphasizing an “inherent contradiction in simultaneously treating diseases that are auto-immune (the immune system attacking the host), and immunodeficiency diseases (like AIDS)… Increasing immune activity actually worsens auto-immune diseases, and suppressing the immune system would worsen AIDS. This is a difficult contradiction to resolve.[iv]
I decided to check PubMed for research that mentions prostate cancer and LDN. I found two abstracts. The first is from a team at the Integrative Medicine Center of New Mexico and involves three case studies of patients with metastatic pancreatic cancer.[v] They were put on intravenous alpha lipoic acid and oral LDN. At the time of publication, the first patient was still alive at 39 months after starting treatment, the second had no evidence of disease (by PET scan) after 5 months of therapy, and the third (who had an additional history of lymphoma and prostate cancer) had clear PET scans after 4 months of therapy. It was unclear if the prostate cancer had been treated, or was active during the protocol, so I could make no conclusion as to whether LDN had any effect on his PCa.
The second study is less than a year old as of this writing, and the authors are from a French research laboratory.[vi] They describe the results of treating 10 chemotherapy-resistant advanced cancer patients (various cancers) with intravenous lipoic acid and LDN as a form of “compassionate metabolic” therapy. An 11th patient with hormone-resistant advanced prostate cancer was treated with the lipoic acid and hormone ablation, but not LDN. Two patients died within two months because their cancer continued to progress. Of the remaining nine, the impact of the study protocol was mixed, and the prostate cancer patient experienced a 90% decrease in his PSA—but again, it was not due to LDN. The authors reported lack of treatment side effects, and concluded that further clinical study was warranted to determine whether the metabolic therapy had merit on its own, or enhanced the effect of previous chemotherapies.
I found no studies specifically on LDN and prostate cancer. While I also found no evidence that LDN does any harm, I still wonder if it does what its promoters claim. I like the biologic theory behind it, but I also believe further research, especially randomized, double-blind studies with larger numbers of patients, is necessary to demonstrate whether the apparent biological effects of LDN on the immune system (i.e. the increased endorphin uptake and consequent up-regulation of immune defense mechanisms) are borne out in human trials.
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
[1] Opioids are a class of medical drugs that block pain receptors, such as morphine, Oxycontin, Percodan, etc. Heroin is an illegal, powerfully addictive opioid, and many prescription drugs are also illegally sold as street drugs. All have the potential to form dependency.
[i] Liu WM, Scott KA, Dennis JL, Kaminska E et al.. Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy. Int J Oncol. 2016 Aug;49(2):793-802.
[ii] Dalgleish AG, Liu WM. The role of immune modulation and anti-inflammatory agents in the management of prostate cancer: A case report of six patients. Oncol Lett. 2022 Jun 7;24(2):247.
[iii] http://www.sciencebasedmedicine.org/low-dose-naltrexone-bogus-or-cutting-edge-science/
[iv] Ibid.
[v] Berkson BM, Rubin DM, Berkson AJ. Revisiting the ALA/N (alpha-lipoic acid/low-dose naltrexone) protocol for people with metastatic and nonmetastatic pancreatic cancer: a report of 3 new cases. Integr Cancer Ther. 2009 Dec;8(4):416-22.
[vi] Schwartz L, Buhler L, Icard P, Lincet H, Steyaert JM. Metabolic treatment of cancer: intermediate results of a prospective case series. Anticancer Res. 2014 Feb;34(2):973-80.
About Dr. Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
