Company: CMND
Filing Date: 2025-01-22
Form Type: 20-F
Source: 0001213900-25-005490
Chunk: 130

Company: Clearmind Medicine Inc.
Filing Date: 2025-01-22
Form: 20-F
Item: Item 4
Chunk 130
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ats (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.

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