Company: CMND
Filing Date: 2025-12-05
Form Type: F-1/A
Source: 0001213900-25-118772
Chunk: 155

Company: Clearmind Medicine Inc.
Filing Date: 2025-12-05
Form: F-1/A
Chunk 155
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Experiment 1): MEAI’s effect on reward was tested using doses ranging from 2.5 to 20 mg/kg. The selection of the high dose was based on a previous pharmacokinetic study ( Volcani Center and Hebrew University Study).The high dose of 20 mg/kg showed low duration in the non-preferred place (sec) which indicates low reward. However, due to unexpected observed adverse clinical signs that occurred at this dose (low body posture, aggressiveness, diarrhea, tremors, and piloerection), a range of lower doses was tested. The second dose tested was 10 mg/kg. A higher duration in the non-preferred place was observed with this dose which indicates that there was a rewarding effect, yet this was still significantly less than cocaine. Therefore, two additional lower doses were tested, 2.5 and 5 mg/kg. At these two doses, the duration in the non-preferred place was negative showing no-reward effect. Overall, the dose that displayed the most non-rewarding effect was 5 mg/kg, therefore, this dose was selected to be tested for efficacy as a treatment for cocaine preference in rats in the following experiments. 93 Determination of MEAI as an Effective Treatment for Cocaine Preference in Rats (Experiment 2): In the second part of this experiment, MEAI’s effectiveness as a treatment for cocaine preference was tested in rats. Based on the previous results, a dose of 5 mg/kg MEAI was selected as the treatment dose, since it had a satisfying non-reward effect. Twelve rats were conditioned with cocaine (15 mg/kg i.p.) and on the day of the test were injected with MEAI (5 mg/kg i.p.), followed by a 10-minute wait in their home cage. The rats were then placed into the middle compartment of the arena for the test. The results were mixed with some animals showing a preference to the non-preferred compartment (negative values) and some animals showing a preference for the preferred compartment (positive values). It was decided to use a K-cluster test to evaluate the data; this test is a method that enables separation of two different sub-groups with statistical significance in a non-biased manner with high integrity. The two groups were divided as values below 100 seconds in a non-preferred compartment (MEAI A) and above 100 seconds (MEAI B). Based on the findings, a higher dose of MEAI (10 mg/kg i.p.) was tested to see if a more