Acute COVID-19 Clinical Trials
There are four clinical trials of Low Dose Naltrexone (LDN) as an acute COVID-19 therapeutic in the United States, two of which are currently recruiting. Statera BioPharma (formerly Cytocom), which calls its formulation STAT-205, is conducting a study at centers in California and Florida of patients with mild symptoms in the first 30 days of the illness, while hospitals in Minnesota are experimenting with LDN and colchicine together. Initial results from a completed study of hospitalized COVID patients in Royal Oak, Michigan are not encouraging with respect to the treatment of severe illness, but adverse side effects reported by the cohort receiving LDN were, interestingly, lower than for the placebo group.
Long COVID (PASC) Clinical Trials
For COVID-19 long haulers wanting to participate in a study of low dose naltrexone, there is only one, run by Ann Arbor, Michigan anti-aging drug supplier AgelessRX. Clinical trial NCT04604704 combines LDN with NAD+ (nicotinamide adenine dinucleotide anion administered by patch) for the treatment of post-COVID syndrome. There are plenty of Low Dose Naltrexone clinical trials, about 50, some of them for post-viral conditions, and there are other interventions being tried for Long COVID, but only the one clinical trial deploys LDN to treat long COVID at this time.Subscribe to the Trialsitenews “COVID-19” ChannelNo spam – we promise
On January 19, 2022, the FLCCC (Front Line COVID-19 Critical Care Alliance) updated its I-RECOVER Protocol for the treatment of long COVID to include Low Dose Naltrexone, with dosing recommendations consistent with those of clinicians using LDN for the treatment of other chronic conditions.
Full dose naltrexone, taken 50mg-100mg at a time, was approved by the U.S. F.D.A. in 1984 to reduce cravings for opiates and opioids. In 1994 its permitted use was expanded to the treatment of alcohol use disorder.
While it’s closely related to Narcan (naloxone), naltrexone is used to block cravings only after a person has quit using narcotics or alcohol by blocking opioid receptors,
mu in particular. Distributors of full-dose naltrexone tablets include Barr Pharmaceuticals of Pomona, NY, and Mallinckrodt Pharmaceuticals of St. Louis, MO.
Much of the early research on naltrexone at both full and low dose was done at Penn State.
Low dose naltrexone (LDN), 0.5mg to 7mg, is used for a surprisingly different purpose than the full dose: pain management and inflammation reduction for chronic disease patients. Many sufferers from fibromyalgia, Crohn’s disease, multiple sclerosis, ME/CFS, AIDS, post-Lyme, and an assortment of other ailments report relief and often general improvement.
Dose being key, attempts to crush or otherwise parse higher dose tablets is not recommended; one must obtain LDN tablets from a compounding pharmacy. There is now sufficient demand that some companies are producing batches and stocking product despite chronic disease pain management being an off-label use.
Naltrexone’s multiple mechanisms of action explain the unusual phenomenon of its dose-dependent applicability. Partial antagonism of opioid receptors has the paradoxical effect of increasing endorphin production, producing an analgesic effect. In addition, naltrexone is an anti-inflammatory, blocking toll-like receptors and crossing the blood-brain barrier to reduce microglial cell activation, reducing brain inflammation.
These multiple mechanisms can be grouped according to the left- and right-handed nature of individual naltrexone molecules. It’s thought that levo- and dextro-isomers of naltrexone would produce different, independently dose-dependent effects, though this has not been experimentally validated in vivo. Only the chimeric form containing both left and right-handed molecules is FDA approved at this time.
According to the Awake Health website the breakdown is:
- Antagonist effect at Toll-like receptors (TLR)
- TLR-4 receptors exist on microglial cells, other macrophages, mast cells
- Activated microglial cells produce proinflammatory cytokines, substance P, nitric oxide
- Inhibition leads to a decreased proinflammatory cascade
- Antagonist effect at opioid receptors
- Small temporary opioid blockade
- Upregulates endogenous opioid production
- Upregulates opioid receptors
- Increased endorphins favorable to the immune system
While there are numerous clinicians and treatment centers utilizing LDN, two organizations stand out as hubs of research and information sharing activity: the LDN Research Trust, a patient-organized nonprofit in the U.K., and the University of Alabama’s Neuroinflammation, Pain and Fatigue Laboratory. Jarred Younger, Ph.D., Director of the lab, has long expressed an interest in developing the dextro-isolate as a therapeutic. To what extent the FDA would regard that as novel, fully investigational drug, in which case it would have to go through a longer approval process but might attract more investor interest than a repurposed drug, is one of several questions to be answered. Allodynic Therapeutics in North Miami, Florida, holds several related patents including one claiming the dextro- isomer.
A current discussion of LDN and LDN therapy can be found on the website of Awake Health, an Ellensburg, Washington clinic. The central Washington location of Awake Health may be far from the Florida patent holder and the University of Alabama but is less distant from another notable center of chronic disease research, Mercer Island-based PolyBio. Other potential players include Soin Therapeutics of Dayton, Ohio, which obtained FDA Orphan Drug designation last year for the use of LDN in the treatment of Complex Regional Pain Syndrome (CRPS), and Sorrento Therapeutics, which aims to run a clinical trial relative to fibromyalgia.
UK-based LDN Research Trust founder Linda Elsegood.
University of Alabama Neuroinflammation, Pain and Fatigue Laboratory director Jarred Younger.