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

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“Ethan B. Russo’s paper of December 1, 2003 explored the concept of a clinical endocannabinoid deficiency (CECD) underlying the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome and other functional conditions alleviated by clinical cannabis.

Available literature was reviewed, including searches via the National Library of medicine database and other sources.

A review of the literature indicates that significant progress has been made since Dr. Ethan B. Russo’s landmark paper, just ten years ago (February 2, 2004). Investigation at that time suggested that cannabinoids can block spinal, peripheral and gastrointestional mechanisms that promote pain in headache, fibromyalgia, irritable bowel syndrome and muscle spasm.

CONCLUSION:

Subsequent research has confirmed that underlying endocannabinoid deficiencies indeed play a role in migraine, fibromyalgia, irritable bowel syndrome and a growing list of other medical conditions. Clinical experience is bearing this out. Further research and especially, clinical trials will further demonstrate the usefulness of medical cannabis. As legal barriers fall and scientific bias fades this will become more apparent.”  http://www.ncbi.nlm.nih.gov/pubmed/24977967

“Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? 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.”  http://www.ncbi.nlm.nih.gov/pubmed/15159679

 

Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model.

“Experimental animal models of migraine have suggested the existence of interactions between the endocannabinoid system and pain mediation in migraine.

Extensive evidence has demonstrated a role for the cannabinoid-1 (CB1) receptor in antinociception.

…recent research suggests that also CB2 receptors, especially located outside the central nervous system, play a role in the perception of pain…

In this study we evaluated the role of CB2 receptors in two animal models of pain that may be relevant for migraine…

CONCLUSION:

These findings suggest that the pharmacological manipulation of the CB2 receptor may represent a potential therapeutic tool for the treatment of migraine.”

http://www.ncbi.nlm.nih.gov/pubmed/24636539

CB2 cannabinoid receptor mediation of antinociception.

“Management of acute pain remains a significant clinical problem. In preclinical studies, CB2 cannabinoid receptor-selective agonists inhibit nociception without producing central nervous system side effects.

The experiments reported here further test the hypothesis that CB2 receptor activation inhibits nociception…

The CB2 receptor-selective agonist produces antinociceptive… activation of CB2 receptors results in antinociception…

…confirm the potential therapeutic relevance of CB2 cannabinoid receptors for the treatment of acute pain.”

http://www.ncbi.nlm.nih.gov/pubmed/16563625

Effect of cannabinoid receptor activation on spreading depression.

“Cannabis has been used for centuries for both symptomatic and prophylactic treatment of different types of headaches including migraine…

Suppression of CSD (cortical spreading depression) by activation of CB1 receptors suggests the potential therapeutic effects of cannabinoids in migraine with aura as well as other CSD-related disorders.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586901/

Therapeutic potential of cannabinoid medicines.

Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Migraine Cure: Marijuana Gives Miracle Relief

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“I guess I was a bit excited when I wrote this and my first article on the subject “Marijuana VS Migraines: Modern Medical Miracle” in Salem-News.com June 30th 2008. Then I was excited about it because the best treatment I had used was Demerol and Benadry injections which knocked the patient out for at least a whole day. This is much better.

Recently in Salem-News.com, a story appeared by Dr. Dianne Stafford, October 3rd 2012 entitled, “Not Just A Headache: Eleven Ways Not To Treat A Migraine”. I hoped that it would be some good stuff but it was a fizzling blah. She didn’t mention one treatment which was a good idea because there are some 20 different pharmaceuticals most of which don’t work for most people. For a migraine sufferer her list is worthless.

I don’t consider myself any great stuff about migraine therapy but I had a real opportunity in this regard when Oregon legalized marijuana for about 10 diseases including severe pain, spasms ( of smooth muscle such as blood vessels in the brain), and nausea and vomiting. Cannabis/marijuana works well for all of these. I must have ended up with about 50 migraine patients who had previously been prescribed or given dozens of poorly working drugs.

At the time no other physician/pharmacologist had published that cannabis/marijuana was effective for migraines, so I published my article. I received 32 responses on 8 pages from July 1st, 2008 till September 1st, 2011. Some are quite short but others are long extolling the effectiveness of cannabis/marijuana therapy. You can read my article and comments. I will reprint a few of the shorter ones:”

More: http://salem-news.com/articles/october112012/marijuana-migraine-pl-2.php

Marijuana for migraines – USAToday

“Does marijuana have medicinal value for migraine headaches and other maladies?

“There is no question that cannabis is beneficial medicinally,” Bearman says. With migraines, “some people say it makes the pain go completely away or can prevent migraines from coming on. Others say it lessens the pain and allows them to focus on other things to get their work done.”

What cannabis does to alleviate migraines is complicated and not completely understood. “But it works on serotonin and dopamine receptors, and has anti-inflammatory activity,” says Russo, who is just finishing a paper for the Journal of Cannabis Therapeutics.

“Basically, it is a multi-modality agent that works on various aspects of migraine in a way that’s really unique. And it’s not just the THC — tetrahydrocannabinol, the psychoactive chemical — that does it. It appears now that it’s the result of the interaction of a combination of other cannabinoids and also the essential oils in the plant.”

Unlike most headache medications, cannabis is unique in that it works as both a preventive agent and an analgesic. “At any point in the migraine, they could use cannabis by smoking, vaporizer, etc., and about 80% of these people get significant or total relief,” he says. “And, if someone has a chronic migraine, daily use in whatever form will often lead to a complete remission.””

http://usatoday30.usatoday.com/life/health/doctor/lhdoc227.htm

The Use of Marijuana or Synthetic Cannabinoids for the Treatment of Headache – MedScape

“Pharmacological preparations of cannabinoid compounds have a variety of therapeutic uses in medicine, including different pain syndromes, but have not been previously reported as beneficial for cluster headache.We present a patient with cluster headache who was refractory to multiple acute and preventive medications but successfully aborted his attacks with recreational marijuana use; subsequent use of dronabinol provided equally effective pain relief. The beneficial effect may be related to the high concentration of cannabinoid receptors in the hypothalamus, which has been implicated as a site of dysfunction in neuroimaging studies of patients with cluster headache.

The plant Cannabis sativa has a long history of medical use in the treatment of pain and spasms, the promotion of sleep, and the suppression of nausea and vomiting. However, in the early 1970s cannabis was classified in the Narcotic Acts in countries all over the world as having no therapeutic benefit; therefore, it cannot be prescribed by physicians or dispensed by pharmacists. In the light of this contradictory situation, an increasing number of patients practice a self-prescription with cannabis products for relieving a variety of symptoms.

  The majority of patients used natural cannabis products such as marihuana, hashish, and an alcoholic tincture; in just 5 cases dronabinol (Marinol) was taken by prescription…

 …this survey demonstrates a successful use of cannabis products for the treatment of a multitude of various illnesses and symptoms. This use was usually accompanied only by slight and in general acceptable side effects…”

http://www.medscape.com/viewarticle/738529

Effects of anandamide in migraine: data from an animal model

“Endocannabinoid system seems to be involved in the modulation of NTG-induced hyperalgesia, and probably, in the pathophysiological mechanisms of migraine…

The study confirms that a dysfunction of the endocannabinoid system may contribute to the development of migraine attacks and that a pharmacological modulation of CB receptors can be useful for the treatment of migraine pain…

By combining our data with the findings available from the literature, we can hypothesize that a dysfunction of the endocannabinoid system may contribute to the development of migraine attacks and that a specific pharmacological modulation of CB1 and CB2 receptors may be useful for the treatment of migraine pain, without deleterious effects, as well as of specific associated symptoms (nausea, in primis).”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072518/

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 legal status of cannabinoids and hallucinogens has for a long time severely inhibited medical research, and there are still no blinded studies on headache subjects, from which we could assess true efficacy.”

http://www.ncbi.nlm.nih.gov/pubmed/23278122