Company: CMND
Filing Date: 2025-01-22
Form Type: 20-F
Source: 0001213900-25-005490
Chunk: 123

Company: Clearmind Medicine Inc.
Filing Date: 2025-01-22
Form: 20-F
Item: Item 4
Chunk 123
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, salivation and piloerection; on day 4, salivation
and piloerection; on day 5, piloerection and lacrimation in female rats only. These adverse clinical signs were resolved spontaneously
on day 6 and no abnormal clinical signs were observed until study termination. MEAI showed no adverse effects at 10 and 30mg/kg/day in
rats, corresponding to the human doses of 1.6 mg/kg/day and 4.8 mg/kg/day, respectively.

In-vitro assessments established that cell viability
was not affected in both rat brain striatum primary neurons and human primary hepatocytes using up to 100 mg/L MEAI. In addition, the
combination of ethanol and MEAI was characterized and revealed that the combination of 6% or 7.5% ethanol with 100 mg/L MEAI displayed
no statistically significant increase in cytotoxic effect. In addition, in the absence of metabolic activation MEAI was considered as
not mutagenic.

National Institute on Drug Abuse Study

In another study, conducted by a researcher from
the National Institute on Drug Abuse, National Institute of Health in 2019 that was published in the scientific journal of Psychopharmacology,
MEAI was screened against 29 targets. In this study the investigators assessed, among other things, the interaction of MEAI, with 29 receptor
targets and compared it with the known literature about MDMA. The reason for the comparison between MEAI and MDMA was that the authors
opined in their study that MEAI and MDMA have similar mechanisms of action, and as such may induce similar effects when ingested. MEAI
was found to have moderate affinities for the 5-HT1a and 5-HT2b receptors, and higher affinities for the α2 subtypes. In addition,
high potency at the serotonin transporter was determined, having 6-fold lower potency at the norepinephrine transporter and 20-fold lower
potency at the dopamine transporter. This suggests that the serotonin receptors family is involved in the mechanism of action of MEAI.
Although MEAI was not tested in human clinical studies with respect to its abuse liability, the authors of this paper were of the opinion
that that based on the mechanism of action of MEAI, it is likely to have less abuse liability compared to MDMA, meaning it has less tendency
to be used in non-medical situations, even sporadically. The authors opinion about MEAI having