Company: MIRA
Filing Date: 2025-07-29
Form Type: PRER14A
Source: 0001641172-25-021434
Chunk: 73

Company: MIRA PHARMACEUTICALS, INC.
Filing Date: 2025-07-29
Form: PRER14A
Chunk 73
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 overeating. THC increases food intake, while CB1 blockers reduce appetite and weight, however central nervous system side effects limit their use. CB1 drives both energy-based and pleasure-driven eating.

CB2 receptors are sparse in a healthy brain but increase in microglia and certain neurons during periods of stress or inflammation. They are more prevalent in peripheral tissues like the gut, fat, and immune cells. Unlike CB1, CB2 does not directly stimulate appetite but may indirectly reduce cravings by lowering inflammation and stress—key triggers for emotional eating. In the brain, CB2 activation reduces neuroinflammation, which can overstimulate reward circuits in obesity or addiction. In the gut and adipose tissue, CB2 curbs inflammatory cytokines, supports insulin sensitivity, and may stabilize appetite signals. While CB1 says “eat more,” CB2 seems to say “regulate,” fine-tuning consumption through immune modulation. 39

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MAO-B

MAO-B, found in the brain (striatum, hypothalamus, astrocytes) and periphery (adipose, liver), breaks down dopamine, phenylethylamine (“PEA”), and trace amines. By clearing dopamine—a key player in reward and satiety—high MAO-B activity may dull satisfaction, increase cravings, and promote overeating. In the hypothalamus, it may alter hunger circuits. MAO-B inhibitors (such as selegiline) boost dopamine and can reduce food intake in animals, though results vary. In humans, Parkinson disease patients on MAO-B inhibitors report appetite shifts, suggesting a craving link. Elevated MAO-B in obese fat tissue may signal oxidative stress, potentially driving emotional eating. Overall, MAO-B may sustain hunger by lowering dopamine and PEA; inhibition might curb appetite, but effects depend on context. (Source: the Journal of Frontiers in Pharmacology)

Interplay: CB1, CB2, and MAO-B

Both CB1 and MAO-B increase the amount of dopamine required by the body through different mechanisms: CB1 increases its release in reward circuits by increasing dopamine cravings, while MAO-B degrades existing dopamine, leaving the body demanding more. In obesity, high CB1 and MAO-B activity can trap individuals in a cycle of dopamine spikes (from food) and crashes, fueling cravings. However, CB2 may counteract this cycle of increased dopamine demand by reducing neuroinflammation that sensitizes reward pathways. Chronic stress and obesity-related inflammation,