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Based on the earlier discussed receptor expression, innervation and their crucial role in behavioral control two mesolimbic nuclei, the VTA and the NAc, became the first targets of studies exploring behavioral consequences of the mesolimbic GLP-1R activation
2024;7:e2423385e2423385

exenatide and dulaglutide show no benefit Reductions in depressive symptoms with semaglutide appear independent of weight loss, suggesting a direct neurobiological mechanism Semaglutide is associated with reduced suicidal ideation in large real-world cohorts Addiction is the perhaps the most exciting signal in the literature: Confirmed reductions across alcohol, nicotine, opioid, and cocaine use disorders Alcohol: reductions in alcohol consumption, craving, relapse rates, alcohol-related diagnoses, and alcohol-related hospitalization, exceeding naltrexone Opioids: 40 to 68% lower overdose risk across multiple large cohorts Nicotine: 12-30% decrease in tobacco use disorder diagnoses, and 40-70% reduction in smoking cessation medication Eating disorders: Binge eating disorder: reduces binge episodes, cravings, and symptom scores Bulimia nervosa: reduces binge-purge frequency and episodes Restrictive eating disorders: numerous case reports document reactivation of past anorexia The psychiatric risks: In patients with a low dopamine, GLP-1s may worsen depression or trigger suicidal ideation, the opposite of the benefit seen in most patients Case reports of anhedonia, emotional flatness, and personality change Psychiatric benefits are most clearly established in patients with pre-existing depression, anxiety, or diabetes

HOW DO SEMAGLUTIDE, (WEGOVY, OZEMPIC) AND TIRZEPATIDE (MOUNJARO) WORK
Lion's Mane supports the gut-brain axis and digestive comfort