Musculoskeletal symptoms, such as arthritis, tendonitis and bursitis, are very common in Systemic Lupus Erythematosus (SLE). Pain and disability from these symptoms can be significant and current treatment options for musculoskeletal pain in SLE include non-steroidal anti-inflammatory medications (NSAIDS), narcotic analgesia and corticosteroids. Each of these is limited by significant potential toxicitie including gastrointestinal bleeding and kidney toxicity in the case of NSAIDS, somnolence, constipation and nausea for narcotics and osteoporosis, osteonecrosis, diabetes, cataracts and atherosclerosis for corticosteroids. Ajulemic acid (AjA) is derived from a class of cannabinoids that retain analgesic and anti-inflammatory properties without the psychotropic effects characteristic of tetrahydrocannabinol (THC;marijuana). AjA has been shown to have potent pain- relieving effects, without psychotropic effects, in animal studies and a clinical trial in human subjects with chronic neuropathic pain. Anti-inflammatory effects of AjA have also been demonstrated in animal models as well as in human subjects and in vitro studies of human inflammatory cells. Thus far, a total of 123 subjects (healthy individuals and patients with neuropathic pain) have received AjA with no serious side effects. The overall purpose of this Phase IIa clinical trial is to evaluate the safety of AjA in SLE patients with mild to moderate musculoskeletal pain and to determine an optimum dose of AjA that will provide maximum benefit and minimal toxicity. Clinical improvement will be determined by assessment of SLE disease activity and changes in pain scales. Studies are also planned to evaluate the mechanisms of action of AjA on circulating inflammatory cells. Based on pre- clinical studies already completed in our laboratory, we expect that AjA will decrease the expression of certain pro-inflammatory proteins in peripheral blood cells and increase the expression of other proteins that enhance the resolution of inflammation.
Musculoskeletal pain due to inflammation is a chronic feature of SLE and current treatments are either not very effective but relatively safe or they are very effective but have lots of side effects. The purpose of this clinical trial is to test the safety ad anti-inflammatory effects of a novel drug, Ajulemic Acid, for the treatment of musculoskeletal pain in lupus patients. Ajulemic Acid is a cannabinoid derivative that does not have psychotropic effects on the brain and we expect that this drug may provide substantial pain relief with anti-inflammatory effects on the immune system that will reduce disease activity in lupus patients.
