Relmada Therapeutic Inc. announced that new preclinical data on its novel psilocybin will be highlighted in a poster presentation at the American Association for the Study of Liver diseases (AASLD) The Liver Meeting(R) 2023, being held November 10-14, 2023, in Boston, MA. The data demonstrate the beneficial effect of non-psychedelic/low dose psilocybin on multiple metabolic parameters in a rodent model of metabolic dysfunction-associated steatotic liver disease (MASLD). Mice were fed a high fructose, high fat diet (HFHFD) for 17 weeks to induce MASLD, along with hyperglycemia, hyperlipidemia and significant weight gain.

One group of MASLD mice (N=10) was treated with low-dose (0.05 mg/Kg) psilocybin daily and a second (N=10) with vehicle daily by oral gavage while continuing on HFHFD. Standard diet-fed mice (N=10) were used as controls. Body-weight and food intake were assessed weekly.

Key statistically significant results in psilocybin-treated mice relative to HFHFD vehicle-treated mice include: Significantly reduced hepatic steatosis; 12% reduction in body weight gain with no reduction in food intake; Significant decrease in fasting blood glucose level and AUC in an Oral Glucose Tolerance Test (OGTT); Additionally, 0.05 mg/Kg psilocybin resulted in: Restoration of plasma and liver triglyceride levels to those of the standard-diet fed mice; Reduced anxiety-like behavior (p<0.05) with no detrimental central nervous system (CNS) effects; Modulation of hepatic genes involved in de novo lipogenesis, glycolysis, ß-oxidation, i.e., SREBP1 (2-fold decrease, p<0.05), ChREBP (2-fold increase, p<0.05 vs. controls) and CPT-1 (3-fold increase, p<0.05). These pleiotropic metabolic effects were demonstrated to be due, in part, to the 5-HT-2A serotonin receptor agonist activity of psilocybin, a mechanism distinct from, and potentially complementary to, the incretin (GLP-1) class of agents.

Additionally, the results show that low-dose psilocin, the pharmacologically active metabolite of psilocybin, reduces lipid accumulation in HepG2 cells in vitro in a 5-HT-2A dependent manner. Relmada intends to enter human studies of its proprietary, non-psychedelic/low dose modified-release formulation of psilocybin for metabolic indications. Leveraging the large amount of safety data already publicly available on psilocybin, the Company plans to commence a single-ascending dose Phase 1 trial in obese patients with steatotic liver disease in early 2024 to define the pharmacokinetic, safety and tolerability profile of Relmada's modified-release psilocybin formulation in this population, followed by a Phase 2a trial in the same patient population to establish clinical proof-of-concept.