Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?
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.
Available literature was reviewed, and literature searches pursued via the National Library of Medicine database and other resources.
Effects of anandamide in migraine: data from an animal model.
Systemic nitroglycerin (NTG) produces spontaneous-like migraine attacks in migraine sufferers and induces a condition of hyperalgesia in the rat 4 h after its administration. Endocannabinoid system seems to be involved in the modulation of NTG-induced hyperalgesia, and probably, in the pathophysiological mechanisms of migraine. In this study, the analgesic effect of anandamide (AEA) was evaluated by means of the formalin test, performed in baseline conditions and following NTG-induced hyperalgesia in male Sprague-Dawley rats. AEA was administered 30 min before the formalin injection. In addition, the effect of AEA (administered 30 min before NTG injection) was investigated on NTG-induced Fos expression and evaluated 4 h following NTG injection. AEA induced a significant decrease in the nociceptive behavior during both phases of the formalin test in the animals treated with vehicle, while it abolished NTG-induced hyperalgesia during the phase II.
Cannabinoids and hallucinogens for headache
Hallucinogens and most cannabinoids are classified under schedule 1 of the Federal Controlled Substances Act 1970, along with heroin and ecstacy. Hence they cannot be prescribed by physicians, and by implication, have no accepted medical use with a high abuse potential. Despite their legal status, hallucinogens and cannabinoids are used by patients for relief of headache, helped by the growing number of American states that have legalized medical marijuana. Cannabinoids in particular have a long history of use in the abortive and prophylactic treatment of migraine before prohibition and are still used by patients as a migraine abortive in particular. Most practitioners are unaware of the prominence cannabis or “marijuana” once held in medical practice. Hallucinogens are being increasingly used by cluster headache patients outside of physician recommendation mainly to abort a cluster period and maintain quiescence for which there is considerable anecdotal success.
The endocannabinoid system and migraine
The recently discovered endocannabinoid system (ECS), which includes endocannabinoids and the proteins that metabolize and bind them, has been implicated in multiple regulatory functions both in health and disease. Several studies have suggested that ECS is centrally and peripherally involved in the processing of pain signals. This finding is corroborated by the evidence that endocannabinoids inhibit, through a cannabinoid type-1 receptor (CB1R)-dependent retrograde mechanism, the release of neurotransmitters controlling nociceptive inputs and that the levels of these lipids are high in those regions (such as sensory terminals, skin, dorsal root ganglia) known to be involved in transmission and modulation of pain signals. In this review we shall describe experimental and clinical data that, intriguingly, demonstrate the link between endocannabinoids and migraine, a neurovascular disorder characterized by recurrent episodic headaches and caused by abnormal processing of sensory information due to peripheral and/or central sensitization.
Variations in the cannabinoid receptor 1 gene predispose to migraine
In animal models endogenous cannabinoids have an inhibitory effect on trigeminovascular activation through the cannabinoid receptor 1 (CB1), although there is no evidence of the potential role of CB1 in human migraine. In this study we applied single marker association and haplotypic trend regression analysis to investigate the relationship between the CB1 gene (CNR1) and headache with migraine symptoms (nausea, photophobia and disability, measured by the ID-migraine questionnaire). We identified our controls (CO=684) as those who have not reported ID-migraine symptoms at all and defined migraine headache sufferers (M=195) as those who reported all three symptoms.
Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It’s Been ….
The use of cannabis, or marijuana, for medicinal purposes is deeply rooted though history, dating back to ancient times. It once held a prominent position in the history of medicine, recommended by many eminent physicians for numerous diseases, particularly headache and migraine. Through the decades, this plant has taken a fascinating journey from a legal and frequently prescribed status to illegal, driven by political and social factors rather than by science. However, with an abundance of growing support for its multitude of medicinal uses, the misguided stigma of cannabis is fading, and there has been a dramatic push for legalizing medicinal cannabis and research. Almost half of the United States has now legalized medicinal cannabis, several states have legalized recreational use, and others have legalized cannabidiol-only use, which is one of many therapeutic cannabinoids extracted from cannabis. Physicians need to be educated on the history, pharmacology, clinical indications, and proper clinical use of cannabis, as patients will inevitably inquire about it for many diseases, including chronic pain and headache disorders for which there is some intriguing supportive evidence.
To review the history of medicinal cannabis use, discuss the pharmacology and physiology of the endocannabinoid system and cannabis-derived cannabinoids, perform a comprehensive literature review of the clinical uses of medicinal cannabis and cannabinoids with a focus on migraine and other headache disorders, and outline general clinical practice guidelines.
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