Psilocybin increased Fos protein expression dose-dependently in the frontal cortex, nucleus accumbens, central and basolateral amygdala, and locus coeruleus of male rats, with the strongest effect in the central amygdala. Fos was expressed in both neurons and oligodendrocytes. The central amygdala, a region critical for emotional processing and learning, may be a key site where psilocybin initiates brain activation leading to neuroplastic changes underlying its therapeutic effects.
Nicotine dependence, primarily from smoking and vaping, is a leading cause of preventable death, and current pharmacotherapies—nicotine replacement, bupropion, and varenicline—have limited efficacy. This chapter reviews serotonin-targeted approaches, including selective serotonin reuptake inhibitors (SSRIs), 5-HT2A receptor agonists like psilocybin, 5-HT2C receptor agonists such as lorcaserin, and 5-HT2A receptor antagonists like pimavanserin. Psilocybin shows the most promise for smoking abstinence, but findings are preliminary and face approval challenges. Preclinical tests indicate distinct profiles for these drugs, and emerging biomarkers may enable personalized smoking cessation treatment.