ANCILLARY IDEAS

I came across a recent publication of a study of some of the 'edge' sciences, that may have some answers to questions that folks are frequently asking. CBDs and OI are what stood out to me, but there is more here. Please read the summary below and/or download the entire article at the end:

Melatonin, angiotensin 1-7, and cannabidiol in refractory autoimmune disease: clinical case series

What Was This Study About? Researchers in Italy tested a three-drug natural combination — melatonin (the sleep hormone), angiotensin 1-7 (a blood-pressure-related peptide with anti-inflammatory properties), and cannabidiol (CBD, a non-psychoactive cannabis compound) — in 70 patients with autoimmune diseases that had stopped responding to standard treatments like steroids and immunosuppressants, or who had declined those therapies.

Why These Three Substances? In autoimmune disease, the immune system is out of balance: one type of immune cell (TH17) becomes overactive and drives inflammation, while the "peacekeeping" cells (called Treg cells) become too weak to control it. All three of these substances have been shown in lab and animal studies to calm down TH17 activity and reduce a key inflammatory signal called IL-17. Melatonin also helps boost the body's own production of angiotensin 1-7, which means using them together may allow lower doses to be effective.

OI Relevance — Shared Immune Pathway: Osteogenesis imperfecta involves chronic low-grade inflammation and collagen-related immune signaling. The TH17/Treg imbalance and elevated IL-17 highlighted in this study are also implicated in bone resorption and connective tissue inflammation more broadly — making this pathway of potential interest for OI-related inflammatory bone disease research, even though OI is not mentioned in this paper.

Who Was in the Study? 

70 patients (57 women, 13 men; ages 19–91) with a range of autoimmune conditions:

Condition                                                                                                # of Patients

Hashimoto's thyroiditis                                                                             24

Multiple sclerosis (MS)                                                                             21

Inflammatory bowel disease                                                                      6

Rheumatoid arthritis                                                                                    5

Sjögren syndrome                                                                                        4

Psoriasis                                                                                                        3

Lupus, scleroderma, mixed connective tissue disease, uveitis           7

What Did Patients Take?                               All taken by mouth, daily:

• Melatonin: 10 mg nightly (50 mg for MS patients)

• Angiotensin 1-7: 0.5 mg twice daily (in a special protective capsule so it survives digestion)

• Cannabidiol (CBD): 20 mg twice daily

What Were the Results? (After 3 Months)

Hashimoto's thyroiditis (24 patients): The antibody that attacks the thyroid dropped by a median of 47%. Two-thirds of patients had a meaningful response (30%+ reduction).

Other autoimmune diseases (25 patients): Antinuclear antibodies (ANAs — a general marker of autoimmune activity) dropped by a median of 56%. About three-quarters of patients responded.

Multiple sclerosis (21 patients): 62% of patients had no new lesions on MRI scans, with stability lasting a median of 46 months (nearly 4 years). Some patients also reported less nerve pain and improved movement.

Inflammation marker (LMR): A blood-test ratio that reflects immune balance was abnormally low in 6 patients having active flares. After treatment, it normalized in 4 of those 6 (67%).

Side effects and tolerability: No significant adverse events. Many patients actually reported feeling better — less fatigue, less anxiety, improved sleep and mood. Psoriasis patients saw skin clearing; rheumatoid arthritis patients reported significant pain reduction.

OI Relevance — Mitochondrial Connection: The paper attributes improvements in fatigue and mood partly to mitochondrial restoration. Melatonin and CBD both act as antioxidants that protect mitochondria — the cell's energy factories. Mitochondrial dysfunction is also increasingly recognized in OI, particularly in severe forms, as part of the chronic cellular stress associated with defective collagen production.

 Important Limitations —  The authors are very clear that this is early, exploratory research.

Key limitations: 

• No control group (no placebo comparison)

• Retrospective — data was gathered from existing records, not a prospective trial

• Mixed bag of conditions analyzed together, not all separately

• IL-17 and Treg cells were never actually measured — the proposed mechanism is inferred

• The authors call for controlled, randomized trials before any clinical conclusions can be drawn Source: Lissoni P, et al. Melatonin, angiotensin 1-7, and cannabidiol in refractory autoimmune disease: clinical case series. Academia Neuroscience and Brain Research 2026;2.

Original article online  https://doi.org/10.20935/AcadNeurosci8343

ORIGINAL ARTICLE HOSTED without express permission  Plain-English Summary prepared by TheOIGuy