Abstract Background: Because many chronic inflammatory and allergic disorders are intimately linked to excessive mast cell (MC) numbers and activation, it is clinically important to understand the physiologic mechanisms preventing excess MC accumulation/degranulation in normal human tissues. Objective: Because endocannabinoids are increasingly recognized as neuroendocrine regulators of MC biology, we investigated how cannabinoid receptor (CB) 1 signaling affects human mucosal-type mast cells (hMMCs). Methods: Using organ-cultured nasal polyps as a surrogate tissue for human bronchial mucosa, we investigated how CB1 stimulation, inhibition, or knockdown affects hMMC biology using quantitative (immuno)histomorphometry and electron microscopy. Results: Kit(+) hMMCs express functional CB1 in situ. Blockade of CB1 signaling (with the specific...