Cancer is the second leading cause of death in the U.S. and is a result of uncontrolled cellular growth, local tissue invasion, and distant metastases. Cancer is a complex disease caused by physical damage, chemical damage, biological damage, genetic alterations, and/or epigenetic alterations. Exposure or damage from a physical, chemical, or biological agent is believed to be the signal for cancer propagation. Additionally, genetic and epigenetic changes and predispositions play a role in the etiology of cancer.
The current body of literature on LDN and cancer explores the relationship between OGF and OGFr and their effect on cellular proliferation in ovarian, pancreatic, colorectal, and squamous cell carcinomas. Short-term LDN was observed to influence the OGF-OGFr axis, which is responsible for the regulation of cell proliferation.38 Many other studies have investigated the use of LDN alone or in combination with standard therapies in ovarian cancer and renal carcinomas with promising results. Donahue, McLaughlin, and Zagon39 observed that the combination of LDN and cisplatin in ovarian tumors enhanced the inhibition of tumorigenesis, depressed DNA synthesis, and reduced angiogenesis. Additionally, LDN seemed to reduce adverse events with cisplatin therapy. Another study confirmed that LDN upregulates OGF and OGFr, inhibiting tumorigenesis and cancer proliferation.40 An alternative theory is that LDN prevents the prolonged cellular state of arrest in response to DNA damage, which places the cells in a state of cytostasis. This state of cytostasis reduces the sensitivity of the cell to treatment, preventing the cell from entering the apoptosis pathway. The intermittent binding of LDN does not block cells from entering this apoptosis pathway.41
Evidence seems to support LDN as an adjunct to current anticancer regimens, both by enhancing the drugs’ anti-tumorigenesis effects and by decreasing the severity of side effects related to chemotherapy regimens.
A case study by Miskoff and Chaudhri42 evaluated LDN in a 50-year-old male with prolonged survival and a history of prostate and lung cancer after a resection of adenocarcinoma in the right upper lobe of the lung. The patient began chemo-radiotherapy with cisplatin and pemetrexed postsurgery. Chemotherapy was stopped after the second treatment session due to intolerable side effects. After numerous additional health challenges, the patient was started on LDN 4.5 mg nightly. Imaging performed following the initiation of LDN has been unremarkable. At the time of publication by study authors, this patient had been on LDN for almost 4 years. More research is needed to assess the clinical efficacy of the use of LDN in these patients.
Autism Spectrum Conditions
Autism spectrum conditions (ASC) are a heterogeneous collection of behavioral disorders with an estimated prevalence of 1 in 68 children in the U.S. One of the theories behind the pathophysiology of ASC is an imbalance of beta-endorphins resulting in behaviors such as decreased socialism, insensitivity to pain, and motor hyperactivity. Brown and Panksepp43 discuss LDN’s role in both immune and psychiatric regulation resulting in improved social bonding, emotional well-being, and relieving symptoms in autism and depression. Furthermore, Roy, Roy, Deb, Unwin, and Roy44 investigated the effects of naltrexone on symptoms in patients with ASC. Participants were given
0.5-2 mg/kg of naltrexone with 77% showing improvement in irritability and hyperactivity compared to placebo. Naltrexone’s effects on endorphins has clinically only been observed with low doses. Given the positive outcomes of the above-mentioned study using traditional dosing, it is logical to believe that LDN would have an equal or possibly more profound effect on ASC symptoms.
Wound Healing and Infection
In their book The Promise of Low Dose Naltrexone Therapy: Potential Benefits in Cancer, Autoimmune, Neurological and Infectious Disorders, Moore et al.45 discuss the difference between the effects of LDN and high-dose naltrexone (HDN). High-dose naltrexone has been observed to have a positive effect on cellular growth due to the selective blockade of the OGF-OGFr axis. The primary cell type in the granulation of cellular tissue is the fibroblast, the activity of which has been shown to be increased by HDN applied as a cream.46 Additionally, in an animal study of wound healing in diabetic rats, topical 0.03% naltrexone cream applied to the wound accelerated DNA synthesis, increased mast cells, enhanced the expression of platelet-derived growth factor, and enhanced vascular endothelial growth factor.47 The complete blockade of the OGF-OGFr axis by HDN appears to increase cellular growth and angiogenesis, both of which are important in wound healing. These are promising results for the use of naltrexone in wound healing, especially in patients with disease states with impaired wound healing, such as diabetes.
Alternatively, LDN has been studied in infection control due to its properties of inhibiting cellular growth through upregulating OGF levels. Tian, Jiao, and Wang et al.48 showed that increased OGF exerted both a prophylactic and protective effect against the influenza A virus in mice. Additionally, LDN has been studied in HIV and hepatitis infections with similar protective results. It has been discussed above how LDN increases OGF levels, thereby explaining the relationship between LDN therapy and viral deterrence. Opioid growth factor receptors also appear to modulate the development of some bacterial species, activation of which seems to downregulate cellular growth. Low- dose naltrexone has been implicated in the prevention of Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus marcescens growth, opening the possibility of using LDN in infection control.45