Synthetic cannabinoid Ajulemic acid exerts potent antifibrotic effects in experimental models of systemic sclerosis

The therapeutic potential of cannabinoids such as THC is grossly limited by their psychoactive effects, leading to a growing interest in the development of synthetic analogs with similar benefits but without activity on the brain. One of such compounds is ajulemic acid (AjA), which can bind to both cannabinoid receptors and the peroxisome proliferator-activated receptor-γ (PPAR-γ) but can’t cross the blood-brain barrier effectively to trigger psychoactive responses.

Recent evidence suggests a key role for cannabinoid receptors as well as PPAR-γ in fibrogenesis, which is the formation of fibrous tissue – a strong tissue consisting of twisted strands of collagens by cells known as fibroblasts. This process, when going unchecked, underlies diseases like systemic sclerosis, also known as scleroderma. More particularly, in systemic sclerosis, the uncontrolled fibrogenesis leads to chronic hardening and tightening of the skin and joint pain. For these reasons, scientists hypothesized that AjA could be a drug molecule targeting abnormal fibrogenesis in patients with scleroderma.

So far, several experiments have supported this hypothesis. First, AjA was found to strongly reduce collagen synthesis by scleroderma fibroblasts in skin cells from patients. This action was reversed completely in the presence of a PPAR-γ blocker, confirming that such reduction resulted from activation of PPAR-γ by AjA. Second, in murine models of scleroderma, when mice received AjA prior to induction of the disease process, abnormal thickening of the skin was significantly prevented. When mice received AjA 3 weeks into the disease, its progression was still moderately hindered.

If you or someone you know suffers from Scleroderma (or Crest Syndrome), and want to learn more about how cannabis may be helpful in providing relief, contact CED Clinic today at Dr. Caplan and his team would be happy to discuss treatment options.


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