*6.3. Human Clinical Trials*

Developing on the favorable results cited in multiple in vivo studies, Ali et al. tested the safety and efficacy of an extract cream made of cannabis seeds in healthy patients and noted significant sebum diminution and erythema reduction while noting possible skin irritation as an adverse effect [188]. A Phase 2 study ran by Botanix Pharmaceuticals evaluating a proprietary synthetic CBD-derived cannabinoid labeled BTX 1503 on more than 350 patients with acne was recently completed, but the results are not yet available [189].

Cannabinoids were clinically tested in diffuse cutaneous systemic sclerosis, in a doubleblind, randomized placebo-controlled study on 42 subjects performed by Spiera et al. [190]. The authors noted that while the side effects included fatigue and vertigo, the patients receiving ajulemic acid had a significant improvement in their clinical scores, with a reduction in the expression of key genes related to inflammation on skin biopsies. Subsequently, a Phase 3 trial was launched in 2018, with an estimated 350 patients receiving either ajulemic acid in 20 mg or 5 mg concentrations, or a placebo [191].

Ajulemic acid was also tested in another Phase 2 trial conducted by Chen et al. for the effectiveness in controlling the inflammation in patients with dermatomyositis [192]. The oral administration of ajulemic acid leads to a decrease of IL-31, IFN-β and -γ, and T-helper cell inflammation, demonstrating effectiveness in the treatment of dermatomyositis skin lesions. Werth et al. developed a Phase 3 study to test the performance of ajulemic acid in dermatomyositis [193].
