Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?

Neuro Endocrinol Lett. Feb-Apr 2004;25(1-2):31-9.

Abstract

Objectives: This study examines the concept of clinical endocannabinoid deficiency (CECD), and the prospect that it could underlie the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis.

Methods: Available literature was reviewed, and literature searches pursued via the National Library of Medicine database and other resources.

Results: Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. The past and potential clinical utility of cannabis-based medicines in their treatment is discussed, as are further suggestions for experimental investigation of CECD via CSF examination and neuro-imaging.

Conclusion: Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.

Publication types

  • Review

MeSH terms

  • Arachidonic Acids / pharmacology
  • Cannabinoid Receptor Modulators / deficiency*
  • Cannabinoids / therapeutic use
  • Endocannabinoids*
  • Fibromyalgia / drug therapy
  • Fibromyalgia / physiopathology*
  • Humans
  • Irritable Bowel Syndrome / drug therapy
  • Irritable Bowel Syndrome / physiopathology*
  • Migraine Disorders / drug therapy
  • Migraine Disorders / physiopathology*
  • Pain / drug therapy
  • Pain / physiopathology*
  • Polyunsaturated Alkamides
  • Serotonin / physiology

Substances

  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Endocannabinoids
  • Polyunsaturated Alkamides
  • Serotonin
  • anandamide