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Clinical Endocannabinoid Deficiency

Clinical Endocannabinoid Deficiency: The Facts

August 23, 2019

Cannabidiol (CBD) seems to impart limitless wellness benefits. The ability of cannabinoids to act as an apparent magic bullet for diverse issues led to the concept of clinical endocannabinoid deficiency (CED). CED means that if the body does not produce enough of its own cannabinoids — or if cannabinoid signaling fails — we may become ill. 


The CED hypothesis suggests that individuals with certain treatment-resistant conditions may have an underperforming endocannabinoid system (ECS). Systemic failure of the ECS may underlie a range of health conditions, most prominently migraine, fibromyalgia, and irritable bowel syndrome [1,2].


Dr. Ethan Russo explained CED in 2004, drawing a parallel to other syndromes that arise from neurotransmitter malfunctions. Specifically, Dr. Russo pointed out that Alzheimer’s is linked to reduced acetylcholine activity; depression is linked to low serotonin; and Parkinsonism is linked to low dopamine. It stands to reason that low/abnormal levels of endocannabinoids, which are ubiquitous neurotransmitters with abundant receptors, may harbor disease [1].


Research supports the CED concept; the endocannabinoid system serves a protective role and safeguards physiological homeostasis. Disruptions in this system may spark pathologies [3,4]. As one example, a study in Neuropsychopharmacology reported that chronic stress led to a deficiency of endocannabinoid signaling [5]. Another study conducted in 2014 on mice found that normalizing endocannabinoid signaling reversed affective disorder (mood/anxiety) [6].


This begs the question — do I have a deficiency? And will CBD help?


The truth is that there is no established litmus test for CED. The concept is relatively young and research is still underway. In a 2016 publication in Cannabis and Cannabinoid Research, Dr. Russo elucidated several potential clinical manifestations:


  • Migraine
  • Fibromyalgia
  • Irritable bowel syndrome
  • Cystic fibrosis
  • Causalgia
  • Brachial plexopathy
  • Glaucoma
  • Post-Traumatic Stress Disorder 
  • Dysmenorrhea
  • Bipolar Disorder


Conditions are based on the criteria of “unfathomed pathophysiological features,” and resistance to conventional treatments [2]. More broadly, criteria include:


  • Hyperalgesic states (increased sensitivity to pain)
  • Diagnoses of exclusion (reached via the process of elimination)
  • Higher risk of depression and anxiety
  • Comorbidity of conditions [2]


Upregulating the ECS with hemp cannabinoids – particularly CBD –  promotes physiological homeostasis and theoretically counters CED with a much-needed kick start. CBD increases levels of anandamide, the natural endocannabinoid associated with pain regulation, mood balance, and inflammation control [7-9]. Hemp-based cannabinoids represent a novel, natural option to activate the ECS and counter any potential deficiencies.


Scientists and medical professionals have yet to develop a diagnostic tool for CED; at present, it is a fairly well-supported hypothesis. The bottom line is that every person has an innate endocannabinoid system. If it malfunctions, the results are unlikely to be positive. CBD and other phytocannabinoids may enhance and boost the ECS to improve overall wellness.



  1. Russo, E. (2004). Clinical Endocannabinoid Deficiency (CECD): Can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuroendocrinology Letters, 25(1-2), 31-39.
  2. Russo, E. B. (2016). Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis and Cannabinoid Research,1(1), 154-165. doi:10.1089/can.2016.0009
  3. Kaur, R., Ambwani, S. R., & Singh, S. (2016). Endocannabinoid System: A Multi-Facet Therapeutic Target. Current Clinical Pharmacology,11(2), 110-117. doi:10.2174/1574884711666160418105339
  4. Mcpartland, J. M., Guy, G. W., & Marzo, V. D. (2014). Care and feeding of the endocannabinoid system: A Systematic review of potential clinical interventions that upregulate the endocannabinoid system. PLoS ONE,9(3). doi:10.1371/journal.pone.0089566
  5. Wang, W., et al. (2010). Deficiency in endocannabinoid signaling in the nucleus accumbens induced by chronic unpredictable stress. Neuropsychopharmacology,35(11), 2249-2261. doi:10.1038/npp.2010.99
  6. Shonesy, B., et al. (2014). Genetic disruption of 2-Arachidonoylglycerol synthesis reveals a key role for endocannabinoid signaling in anxiety modulation. Cell Reports,9(5), 1644-1653. doi:10.1016/j.celrep.2014.11.001
  7. Clapper, J. R., et al. (2010). Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nature Neuroscience, 13, 1265. Retrieved from
  8. Gobbi, G., et al. (2005). Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Proceedings of the National Academy of Sciences of the United States of America, 102(51), 18620 LP – 18625.
  9. Maccarrone, M., & Finazzi-Agró, A. (2003). The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis. Cell Death & Differentiation, 10(9), 946–955.



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