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.

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