The theory of clinical endocannabinoid deficiency (CED) was presented in manifest similarly in certain disorders that display predictable clinical features The use, by its sufferers, of cannabis-based agents to treat IBS has. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and. What is the Clinical Endocannabinoid Deficiency Syndrome? . why there is research underway to try and determine if CBD can help Alzheimer's patients.
Help? Syndrome: Clinical Deficiency CBD Endocannabinoid Can
We currently know of two main cannabinoid receptors, the CB1 and CB2 receptors, and the likelihood of discovering more cannabinoid receptors is strong. CB1 receptors are mostly located in the nervous system, connective tissues, gonads, glands, and organs. CB2 receptors are mostly found in the immune system.
In fact, the reason we can even absorb these chemicals in the first place is because our body produces its own cannabinoids naturally — albeit in different forms than the cannabinoids we take into our bodies when using cannabis products.
Our body produces its own cannabinoids called endocannabinoids. The most well researched endocannabinoids are anandamide and 2-arachidonoylglycerol 2-AG. To simplify the concept of endocannabinoids: Anandamide and 2-AG are categorized as endocannabinoids because they are produced within the human organism; THC and CBD are called phytocannabinoids because they are produced within plants. We rely on endocannabinoids for homeostasis, as they handle functions like cell development, healing, pain mitigation and behavior.
For this reason, our body contains endocannabinoid receptors in various areas, such as the brain, cells and tissues that absorb and utilize cannabinoids accordingly. In doing so, we retain a certain balance homeostasis that allows us to function in a healthy way. In a June interview , Russo gives an explanation of his theory:.
Well, we already knew that. But a paper in Nature Neuroscience suggests that nutrition could be at least one contributing factor — specifically as it relates to omega-3 fatty acids scientifically referred to as n-3 PUFAs.
Russo was exploring migraines, fibromyalgia and IBS. Examining these conditions provides a wealth of critical information that could open the door to potential solutions or treatments. Pharmacology , toxicolo gy, and thera peutic potential. Medic al cannabis potency testing proje ct.
Neurolo gy ; North Am ; 2 8: Fib romyalgia and hea dache. Their comm on clues. Cephalalgia ; 18 Sup pl. Eur J Pharmacol ; Hypoa ctivity of the spi-. Eur J Pharm acol ; 3 Cannabin oids red uce hyper-. The cannabinoi d r eceptor agonist WIN 55, mesylate blocks.
Local administration of delta 9-tetrahyd rocannab-. Cannabinoi d WIN 55 ,—2 inhibit s the. Neuroph ysiol ; Schatz AR, et al. Gastrointestinal afferents as targets of novel drugs for. Molecular targets for cannabidiol and its synthetic ana-. Br J Pharmacol ;. Cannabinoi ds an d the gastr ointestinal tract. J Comp Neurol ; Cannabino id CB1-receptor me diated regulati on of gastrointe stinal. In teraction of deltat etra-. Pharm Pharmacol ; Cannabin oids for g astrointestin al dise ases: Expert Opin Investig Drugs ;.
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Br J Pha rmacol ; 14 0: Char acterization of a nove l endocann abinoid , virodhamin e,. J Pharmacol Exp Ther. Cann abis-From pari ah to prescription. Prospe cts for new cann abis-based. J ournal of Cannabis Ther apeutics ; 1: Cannabis and cannabinoi ds as. Pharm aceutical Press , Lond on. Donovan's successes in migraine and a variety of neuropathic pain syndromes were a landmark at the time and included the first reports of cannabis treatment for trigeminal neuralgia, which to this day remains a thorny therapeutic challenge.
Modern studies of neuropathic pain support application of cannabis-based medicines for both central Rog et al. As a footnote, Donovan continued his experiments with cannabis, publishing a later account in documenting another personal experience plus success in two additional cases of facial neuralgia Donovan Richard Greene left practice in ill health in Anonymous Along with his predecessor, Donovan, he may be seen as a pioneer of cannabis treatment of migraine, a diagnosis which remains extremely problematic today, and whose pathophysiology seems intimately related to a disturbance of the endocannabinoid system Russo ; Russo ; Sarchielli et al.
History of Cannabis as Medicine: Cannabis or hemp has been employed medicinally in Ireland since at least the Anglo-Saxon era, more than years ago. Its use came to the fore, however when William B.
His knowledge, acquired through application of the scientific method combining ethnobotanical teachings, animal experimentation and clinical observations in humans, was quickly shared with colleagues in Ireland and England.
This led in turn to rapid advances in therapeutics by Michael Donovan in neuropathic pain states, Dominic Corrigan in chorea and trigeminal neuralgia, Fleetwood Churchill in uterine hemorrhage, and Richard Greene in the use of cannabis as a prophylactic treatment of migraine.
In each instance the observations of these past treatments are examined in light of 21st century advances in pathophysiology so that their rationale and scientific basis are clarified. The venerable Irish tradition of cannabis research is being carried on contemporaneously by numerous prominent scientists with the promise of important advancements yet to come.
This pattern of responses could have been a function of characteristics of the software user interface e. According to the endocannabinoid deficiency theory, many mental and physical health disturbances result from the dysregulation of the body's innate endocannabinoid system ECS; Smith and Wagner, ;Di Marzo et al. The ECS consists of natural ligands e.
The Releaf AppTM mobile software application app data was used to measure self-reported effectiveness and side effects of medical cannabis used under naturalistic conditions.
Releaf AppTM responders used cannabis to treat myriad health symptoms, the most frequent relating to pain, anxiety, and depressive conditions. Significant symptom severity reductions were reported for all the symptom categories, with mean reductions between 2. Patient-managed cannabis use is associated with clinically significant improvements in self-reported symptom relief for treating a wide range of health conditions, along with frequent positive and negative side effects. A theory of Clinical Endocannabinoid Deficiency CED , first described by Russo, posits that migraine, fibromyalgia, irritable bowel syndrome and comorbid anxiety may be related manifestations of reduced endocannabinoid tone, specifically AEA and 2-AG levels [70, 71].
These conditions frequently occur together, and a growing body of evidence suggests that they respond well to cannabinoid therapy, particularly THC . The variants were evaluated for association with phenotypes similar to those observed in the orthologous gene knockouts in mice. Heterozygous rare coding variants in CNR1, which encodes the type 1 cannabinoid receptor CB1 , were found to be significantly associated with pain sensitivity especially migraine , sleep and memory disorders—alone or in combination with anxiety—compared to a set of controls without such CNR1 variants.
Similarly, heterozygous rare variants in DAGLA, which encodes diacylglycerol lipase alpha, were found to be significantly associated with seizures and neurodevelopmental disorders, including autism and abnormalities of brain morphology, compared to controls. Diacylglycerol lipase alpha synthesizes the endocannabinoid 2-AG in the brain, which interacts with CB1 receptors.
The phenotypes associated with rare CNR1 variants are reminiscent of those implicated in the theory of clinical endocannabinoid deficiency syndrome. The severe phenotypes associated with rare DAGLA variants underscore the critical role of rapid 2-AG synthesis and the endocannabinoid system in regulating neurological function and development. Mapping of the variants to the 3D structure of the type 1 cannabinoid receptor, or primary structure of diacylglycerol lipase alpha, reveals clustering of variants in certain structural regions and is consistent with impacts to function.
We briefly review evidence on the impact of environmental forces, particularly the effect of autoimmune activity, in the expression of schizophrenic profiles and the role of Cannabis therapy for regulating immunological functioning. A review of the literature shows that phytocannabinoid consumption may be a safe and effective treatment option for schizophrenia as a primary or adjunctive therapy.
Emerging research suggests that Cannabis can be used as a treatment for schizophrenia within a broader etiological perspective that focuses on environmental, autoimmune, and neuroinflammatory causes of the disorder, offering a fresh start and newfound hope for those suffering from this debilitating and poorly understood disease.
Cannabis sativa active compounds are extensively studied for their therapeutic effects, beyond the well-known psychotropic activity. Sativa is used to treat different medical indications, such as multiple sclerosis, spasticity, epilepsy, ulcerative colitis and pain. Simultaneously, basic research is discovering new constituents of cannabis-derived compounds and their receptors capable of neuroprotection and neuronal activity modulation.
The function of the various phytochemicals in different therapeutic processes is not fully understood, but their significant role is starting to emerge and be appreciated. In this review, we will consider the structure-activity relationship SAR of cannabinoid compounds able to bind to cannabinoid receptors and act as therapeutic agents in neuronal diseases, e. Abschlussbericht der Evaluation des Trainingscamps Lothar Kannenberg.
Medical cannabis for the treatment of chronic pain and other disorders: Oct Pol Arch Med Wewn. Recently, many countries have enacted new cannabis policies, including decriminalization of cannabis possession, medical cannabis legalization, and legalization of recreational cannabis. In this context, patients and their physicians have had an increasing number of conversations about the risks and benefits of cannabis.
While cannabis and cannabinoids continue to be evaluated as pharmacotherapy for medical conditions, currently, the best evidence exists for the following medical conditions: We also reviewed the current state of evidence for cannabis and cannabinoids for a number of other medical conditions while addressing the potential acute and chronic effects of cannabis use, which are issues that physicians must consider before making an official recommendation on the use of medical cannabis to a patient.
As patient requests for medical cannabis increase, physicians must become knowledgeable on the science of medical cannabis and open to a discussion about why the patient feels that medical cannabis may be helpful to them.
Both the kynurenine and the endocannabinoid systems are involved in several neurological disorders, such as migraine and there are increasing number of reports demonstrating that there are interactions of two systems.
Although their cooperation has not yet been implicated in migraine, there are reports suggesting this possibility. Additionally, the individual role of the endocannabinoid and kynurenine system in migraine is reviewed here first, focusing on endocannabinoids, kynurenine metabolites, in particular kynurenic acid. Finally, the function of NMDA and cannabinoid receptors in the trigeminal system—which has a crucial role in the pathomechanisms of migraine—will also be discussed.
The interaction of the endocannabinoid and kynurenine system has been demonstrated to be therapeutically relevant in a number of pathological conditions, such as cannabis addiction, psychosis, schizophrenia and epilepsy. Accordingly, the cross-talk of these two systems may imply potential mechanisms related to migraine, and may offer new approaches to manage the treatment of this neurological disorder.
Cannabis for Pain and Headaches: Apr Curr Pain Headache Rep. Marijuana has been used both medicinally and recreationally since ancient times and interest in its compounds for pain relief has increased in recent years. The identification of our own intrinsic, endocannabinoid system has laid the foundation for further research. Synthetic cannabinoids are being developed and synthesized from the marijuana plant such as dronabinol and nabilone. Nabiximols is a cannabis extract that is approved for the treatment of spasticity and intractable pain in Canada and the UK.
Further clinical trials are studying the effect of marijuana extracts for seizure disorders. Phytocannabinoids have been identified as key compounds involved in analgesia and anti-inflammatory effects. Other compounds found in cannabis such as flavonoids and terpenes are also being investigated as to their individual or synergistic effects.
This article will review relevant literature regarding medical use of marijuana and cannabinoid pharmaceuticals with an emphasis on pain and headaches. The analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome.
Feb Aliment Pharmacol Therapeut. Background Intestinal immune activation is involved in irritable bowel syndrome IBS pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation.
Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation. These three have much in common. All of them cause an increased sensitivity to pain and all must be diagnosed subjectively by a process of exclusion, there being no objective tissue or lab findings for any one of them. And they often overlap, with patients presenting with some combination of the three quite often.
Currently, several types of pharmaceuticals are used to treat migraines. Pain relievers like ibuprofen, aspirin, caffeine, and acetaminophen may help mild migraines but regular use of these can cause problematic side effects that include bleeding stomach ulcers and new headaches caused by medication over-use.
Triptans like Imitrex are injectables that block blood vessels to the brain, aborting the onset of migraines if taken early enough.
Ergotamine combined with caffeine can be used if the migraine lasts more than 48 hours, but this combination can also exacerbate the nausea and vomiting that often occurs. Narcotics, steroids, and anti-nausea medicines are prescribed for persistent painful migraines. Pharmaceuticals are sometimes helpful in preventing migraine headaches.
Blood pressure medications, anti-depressants, anti-seizure medications, and Botox have all been used with varying rates of success. Some of these are quite effective, but each has its own set of possible side effects. For years cannabis was used to treat migraines; it was prescribed extensively in Western medicine between and Queen Victoria used it, and patients still use cannabis to prevent and treat migraine headaches. The trigeminovascular system see image below is considered by many to be at the root of migraine pathophysiology, both through neurons and blood vessels.
CB1 receptors are dense in the trigeminovascular system and research on endocannabinoids in these areas indicates an important role of the ECS in migraine episodes.
The endocannabinoid anandamide inhibits the trigeminovascular system as part of its modulating functions, and analyzation of cerebrospinal fluid in chronic migraineurs revealed significantly lower levels of circulating anandamide in those patients. Inflammation, serotonin, dopamine and depleted beta-endorphins in the central nervous system contribute to migraine syndromes, all of which are modulated by the ECS.
All this lends credence to the link between migraines and dysfunction of the Endocannabinoid System. Anyone with fibromyalgia knows the frustration of diagnosing and treating this disabling condition. Fibromyalgia is the most common diagnosis in American rheumatology practices. Over time, these painful areas intensify pain perception in the brain leading to disturbances in sleep, dysfunction of the nervous system, and depression.
Failure in the Endocannabinoid System: Theory or Reality?
We all want to hear that cannabis can help us with medical issues. But this Clinical endocannabinoid deficiency (CECD) is implicated in a spectrum of disorders. As you Can Cannabis Help With Irritable Bowel Syndrome?. Endocannabinoid deficiency is a theory for the symptoms and conditions receptors of the endocannabinoid system to elicit chemical responses that help Russo believes cannabinoids from cannabis plants like hemp are. Clinical endocannabinoid deficiency (CECD) has been studied in And when your signaling fails to function at proper levels, an endocannabinoid deficiency can result. And boosting your ECS may help diminish the symptoms and CBD for the most comprehensive support of your Endocannabinoid.