Company: MIRA
Filing Date: 2025-08-08
Form Type: DEFM14A
Source: 0001641172-25-022816
Chunk: 186

Company: MIRA PHARMACEUTICALS, INC.
Filing Date: 2025-08-08
Form: DEFM14A
Chunk 186
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acco”. www.who.int. 2024-07-31. Retrieved 2024-10-04.

2 Doll, Richard; Peto, Richard; Boreham, Jillian; Sutherland, Isabelle (2004-06-22). “Mortality in relation to smoking: 50 years’ observations on male British doctors

3 Banks, Emily; Joshy, Grace; Weber, Marianne F; Liu, Bette; Grenfell, Robert; Egger, Sam; Paige, Ellie; Lopez, Alan D; Sitas, Freddy; Beral, Valerie (2015-02-24).”Tobacco smoking and all-cause mortality in a large Australian cohort study: findings from a mature epidemic with current low smoking prevalence”. BMC Medicine

4 World Health Organization (2024-01-16). WHO global report on trends in prevalence of tobacco use 2000–2030

5 Moylan, Steven; Jacka, Felice N; Pasco, Julie A; Berk, Michael (2012). “Cigarette smoking, nicotine dependence and anxiety disorders: a systematic review of population-based, epidemiological studies”. BMC Medicine.

| Moore Financial Consulting |

| SKNY Pharmaceuticals, Inc. | April 2025   |
| Valuation                  | Page 8 of 25 |

Mechanism of Nicotine Dependence

Nicotine, a parasympathomimetic stimulant, exerts its effects by binding to nicotinic acetylcholine receptors in the brain. This interaction triggers the release of dopamine and other neurotransmitters associated with pleasure and reward. Chronic nicotine exposure leads to neuroplastic changes in the brain’s reward system, including an increase in the number of nicotine receptors (upregulation) as a response to initial receptor desensitization. This adaptation contributes significantly to the development of tolerance and dependence. Genetic factors also play a role in susceptibility to nicotine dependence, with specific genetic markers for nicotinic receptors being implicated.

Upon cessation of nicotine use, the brain experiences a lack of stimulation of these upregulated receptors, leading to the onset of withdrawal symptoms such as cravings, irritability, anxiety, and difficulty concentrating. These symptoms often lead to a relapse in individuals attempting to quit.

Treating Nicotine Dependence

Evidence-based treatments are available to aid in quitting nicotine dependence and tobacco use. These include:

Medications:

| ● | Nicotine                                                                                      
 Replacement Therapy (NRT): Provides nicotine without the harmful components of tobacco (e.g