Formulations and treatments are provided for selectively stimulating receptors of the endocannabinoid system (ECS). The formulations include non-cannabis, plant-based agents from readily available herbs, spices and other flavonoid-containing plants. The formulations and treatments can be designed to modulate the ECS so as to achieve a variety of health and wellness effects without incurring various undesirable limitations associated with cannabis. Treatments can be developed rapidly by selecting plant agents that mimic ECS effects associated with established medical agents.