Tonic signaling

Tonic signaling refers to sustained, baseline activity of a signaling system, as distinguished from transient phasic responses to discrete stimuli. In the ECS, tonic signaling is produced by continuous low-level release of endocannabinoids, constitutive receptor activity, and ongoing balance between biosynthetic and degradative enzymes. Elevating endocannabinoid tone pharmacologically (FAAH or MAGL inhibition; exogenous CB1 agonists) or dampening it (antagonists, inverse agonists) alters baseline mood, pain thresholds, stress reactivity, and appetite. Russo (2016, Cannabis and Cannabinoid Research 1:154) revisited the "clinical endocannabinoid deficiency" (CED) hypothesis, proposing that low endocannabinoid tone contributes to migraine, fibromyalgia, and irritable bowel syndrome. ⚠️ CED remains a hypothesis — biomarker evidence (CSF AEA reductions in migraine; altered FAAH activity in fibromyalgia) is suggestive but not definitive. → See also: Endocannabinoid system, FAAH, Homeostasis.