Company: CMND
Filing Date: 2025-12-05
Form Type: F-1/A
Source: 0001213900-25-118772
Chunk: 151

Company: Clearmind Medicine Inc.
Filing Date: 2025-12-05
Form: F-1/A
Chunk 151
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 that MEAI’s main inhibition effect was obtained on 5-HT agonist radioligand, reaching a 76.8% inhibition of 5-HT2b receptor (compared to 100% inhibition with DOI), 62.6% inhibition of 5-HT1A receptor (compared to 100% inhibition with 8-OH-DPAT) and 53.6% inhibition of 5-HT2A receptor (compared to 100% inhibition with DOI). To rule out a possible agonist effect of MEAI on the 5-HT2b receptor, an additional study was conducted, in which the effect of MEAI on calcium flux on the 5-HT2b receptor in agonist format was evaluated in a dose response manner (using 10 concentrations of MEAI ranging between 0.0005 to 10µM). Results showed a maximal response of 18% while serotonin induced 100% maximal response. These results indicate that MEAI is not considered an agonist at the 5-HT2b receptor. Collectively, these results are in line with the previous published reports and further support the safety of MEAI. 91 Hebrew University Study: MEAI’s Effect on binge-eating, Obesity, and its Metabolic Complications MEAIs effect on high fat diet induced obesity was evaluated in mice model mimicking binge eating disorder. For this purpose, an in vivo study was conducted in three phases: in the first phase, the effective dose of MEAI in producing positive metabolic changes in an acute mice model was determined. In the second phase, the efficacy of MEAI was evaluated in high fat diet induced obesity following 28 daily doses of MEAI at the effective dose. In the third phase MEAIs effect on anhedonia, or the decreased ability to experience pleasure, (represents one of the core symptoms of depression which is often associated with binge-behavior) was assessed by the sucrose preference test (SPT) (a reward-based test used as in indicator of anhedonia). In the first phase four groups of adult male mice (n=8 mice per group, total of 32 animals) received a single dose of either vehicle or MEAI by oral gavage (either 40, 60 or 100 mg/kg). Drug tolerability, food and water intake, activity respirometric parameters (respiratory quotient, rate of oxygen consumption, rate of carbon dioxide emission, total energy expenditure, fat oxidation, carbohydrate oxidation) were monitored