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CBD News 11/11/2016

Patient Survey: Cannabis in the Treatment of Age-Related Pain

cannabis and age-related pain
By on November 03, 2016

Pain affects one’s mood, memory, relationships, and overall quality of life. Chronic pain can cause frustration, depression, anger, social isolation, anxiety, poor sleep, and other health risks. Fifty percent of older adults who live on their own and 75-85 percent of the elderly in care facilities reportedly suffer from chronic pain.

This survey—a collaboration between Care By Design and Project CBD—sought to answer several questions: How satisfied are patients with cannabis as an analgesic? How does medical marijuana compare to other pain management approaches, in particular, opiates? How do the most common pain management therapies compare in terms of their impact on quality of life?

Eight hundred people, most between 50 to 70 years old, responded to the survey. Over 80 percent reported that they were suffering from chronic pain; close to half reported suffering from acute pain.

A significant decrease in opiate usage among elderly patients on cannabis therapy was the study’s most notable finding. Over half of respondents reported that they had used both cannabis and opiates for pain management. Of this subgroup, 91 percent said they used fewer or no opiates after beginning cannabis therapy. Sixty-three percent said that they went off opiates altogether.

Other Key Findings:

  • A striking number of patients (around half) reported that opiates had a negative impact on overall wellbeing, and resulted in worsening mood, energy, functional ability and sleep.
  • Cannabis was the only therapeutic approach for which there were no reports of worsening pain. In contrast, surgery, exercise, and nerve blockers benefited some but resulted in increased pain in a significant minority of survey participants.
  • There were no significant differences in outcomes for patients using plant-derived high THC products compared to whole plant CBD-rich products; both types of cannabis were found to be highly effective in managing pain.
  • The most common method of cannabis administration was vaporization, which is generally a safe mode of administration—barring additives and thinning agents that can be found in low quality vaping products.

According to this patient survey, cannabis therapy appears to be an effective pain management tool with few negative side effects. Patient-reported outcomes of cannabis’ efficacy together with its low side effect profile suggest that it should be considered as a first-line treatment for pain and/or as an adjunct treatment to opiates rather than as a medication of last resort.

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CBD News 9/13/2016

The cannabinoid receptor agonist WIN55.212 reduces consequences of status epilepticus in rats.

Abstract

An acute brain insult can cause a spectrum of primary and secondary pathologies including increased risk for epilepsy, mortality and neurodegeneration. The endocannabinoid system, involved in protecting the brain against network hyperexcitability and excitotoxicity, is profoundly dysregulated by acute brain insults. We hypothesize that post-insult dysregulation of the endocannabinoid signaling may contribute to deleterious effects of an acute brain injury and potentiation of endocannabinoid transmission soon after an insult may reduce its pathological outcomes. Effects of an acute post-insult administration of the endocannabinoid receptor agonist WIN55,212-2 on early seizure occurrence, animal mortality and hippocampal cell loss were studied in the lithium-pilocarpine status model. A single dose of WIN55,212-2 (5mg/kg) administered four hours after the end of status epilepticus (SE) reduced the incidence of early seizures during the first two post-SE days though did not change their duration and latency. Brief 4-6-Hz spike-wave discharges appeared de novo in the latent post-SE period and the acute administration of WIN55,212-2 also reduced the incidence of the epileptiform events. A single dose of WIN55,212-2 administered soon after SE improved survival of animals and reduced cell loss in the dentate hilus but did not prevent appearance of spontaneous recurrent seizures in the chronic period. Thus, a brief pharmacological stimulation of the endocannabinoid system soon after a brain insult exerts beneficial effects on its pathological outcome though does not prevent epileptogenesis.

Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:

endocannabinoid system; epilepsy; mortality; neurodegeneration; spike–wave discharges; status epilepticus

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CBD News 9/8/2016

CBD Misconceptions

Cannabis misconceptions, marijuana misinformation
By  

Updated: August 2, 2015

It doesn’t get you high, but it’s causing quite a buzz among medical scientists and patients. The past year has seen a surge of interest in cannabidiol (CBD), a non-intoxicating cannabis compound with significant therapeutic properties. Numerous commercial start-ups and internet retailers have jumped on the CBD bandwagon, touting CBD derived from industrial hemp as the next big thing, a miracle oil that can shrink tumors, quell seizures, and ease chronic pain—without making people feel “stoned.” But along with a growing awareness of cannabidiol as a potential health aid there has been a proliferation of misconceptions about CBD.

  1. “CBD is medical. THC is recreational.” Project CBD receives many inquiries from around the world and oftentimes people say they are seeking “CBD, the medical part” of the plant, “not THC, the recreational part” that gets you high. Actually, THC, “The High Causer,” has awesome therapeutic properties. Scientists at the Scripps Research Center in San Diego reported that THC inhibits an enzyme implicated in the formation of beta-amyloid plaque, the hallmark of Alzheimer’s-related dementia. The federal government recognizes single-molecule THC (Marinol) as an anti-nausea compound and appetite booster, deeming it a Schedule III drug, a category reserved for medicinal substances with little abuse potential. But whole plant marijuana, the only natural source of THC, continues to be classified as a dangerous Schedule I drug with no medical value.
  2. “THC is the bad cannabinoid. CBD is the good cannabinoid.” The drug warrior’s strategic retreat: Give ground on CBD while continuing to demonize THC. Diehard marijuana prohibitionists are exploiting the good news about CBD to further stigmatize high-THC cannabis, casting tetrahydrocannabinol as the bad cannabinoid, whereas CBD is framed as the good cannabinoid. Why? Because CBD doesn’t make you high like THC does. Project CBD categorically rejects this moralistic, reefer madness dichotomy in favor of whole plant cannabis therapeutics. (Read the foundational science paper: A Tale of Two Cannabinoids.)
  3. “CBD is most effective without THC.” THC and CBD are the power couple of cannabis compounds—they work best together. Scientific studies have established that CBD and THC interact synergistically to enhance each other’s therapeutic effects. British researchers have shown that CBD potentiates THC’santi-inflammatory properties in an animal model of colitis. Scientists at the California Pacific Medical Center in San Francisco determined that a combination of CBD and THC has a more potent anti-tumoral effect than either compound alone when tested on brain cancer and breast cancer cell lines. And extensive clinical research has demonstrated that CBD combined with THC is more beneficial forneuropathic pain than either compound as a single molecule.
  4. “Single-molecule pharmaceuticals are superior to ‘crude’ whole plant medicinals.” According to the federal government, specific components of the marijuana plant (THC, CBD) have medical value, but the plant itself does not have medical value. Uncle Sam’s single-molecule blinders reflect a cultural and political bias that privileges Big Pharma products. Single-molecule medicine is the predominant corporate way, the FDA-approved way, but it’s not the only way, and it’s not necessarily the optimal way to benefit from cannabis therapeutics. Cannabis contains several hundred compounds, including various flavonoids, aromatic terpenes, and many minor cannabinoids in addition to THC and CBD. Each of these compounds has specific healing attributes, but when combined they create what scientists refer to as a holistic “entourage effect,” so that the therapeutic impact of the whole plant is greater than the sum of its single-molecule parts. The Food and Drug Administration, however, isn’t in the business of approving plants as medicine. (See the scientific evidence.)
  5. “Psychoactivity is inherently an adverse side effect.” According to politically correct drug war catechism, the marijuana high is an unwanted side effect. Big Pharma is keen on synthesizing medically active marijuana-like molecules that don’t make people high—although it’s not obvious why mild euphoric feelings are intrinsically negative for a sick person or a healthy person, for that matter. In ancient Greece, the word euphoria meant “having health,” a state of well-being. The euphoric qualities of cannabis, far from being an unwholesome side effect, are deeply implicated in the therapeutic value of the plant. “We should be thinking of cannabis as a medicine first,” said Dr. Tod Mikuriya, “that happens to have some psychoactive properties, as many medicines do, rather than as an intoxicant that happens to have a few therapeutic properties on the side.”
  6. “CBD is legal in all 50 states.” Purveyors of imported, CBD-infused hemp oil claim it’s legal to market their wares anywhere in the United States as long as the oil contains less than 0.3 percent THC. Actually, it’s not so simple. Federal law prohibits U.S. farmers from growing hemp as a commercial crop, but the sale of imported, low-THC, industrial hemp products is permitted in the United States as long as these products are derived from the seed or stalk of the plant, not from the leaves and flowers. Here’s the catch: Cannabidiol can’t be pressed or extracted from hempseed. CBD can be extracted from the flower, leaves, and, only to a very minor extent, from the stalk of the hemp plant. Hemp oil start-ups lack credibility when they say their CBD comes from hempseed and stalk. Congress may soon vote to exempt industrial hemp and CBD from the definition of marijuana under the Controlled Substances Act. Such legislation would not be necessary if CBD derived from foreign-grown hemp was already legal throughout the United States. 
  7. “'CBD-only’ laws adequately serve the patient population.” Fifteen U.S. state legislatures have passed “CBD only” (or, more accurately, “low THC”) laws, and other states are poised to follow suit. Some states restrict the sources of CBD-rich products and specify the diseases for which CBD can be accessed; others do not. Ostensibly these laws allow the use of CBD-infused oil derived from hemp or cannabis that measures less than 0.3 percent THC. But a CBD-rich remedy with little THC doesn’t work for everyone. Parents of epileptic children have found that adding some THC (or THCA, the raw unheated version of THC) helps with seizure control in many instances. For some epileptics, THC-dominant strains are more effective than CBD-rich products. The vast majority of patients are not well served by CBD-only laws. They need access to a broad spectrum of whole plant cannabis remedies, not just the low THC medicine. One size doesn’t fit all with respect to cannabis therapeutics, and neither does one compound or one product or one strain. (Read more: Prohibition’s Last Gasp: “CBD Only.”)
  8. “CBD is CBD—It doesn’t matter where it comes from.” Yes it does matter. The flower-tops and leaves of some industrial hemp strains may be a viable source of CBD (legal issues notwithstanding), but hemp is by no means an optimal source of cannabidiol. Industrial hemp typically contains far less cannabidiol than CBD-rich cannabis. Huge amounts of industrial hemp are required to extract a small amount of CBD, thereby raising the risk of toxic contaminants because hemp is a “bio-accumulator” that draws heavy metals from the soil. Single-molecule CBD synthesized in a lab or extracted and refined from industrial hemp lacks critical medicinal terpenes and secondary cannabinoids found in cannabis strains. These compounds interact with CBD and THC to enhance their therapeutic benefits. (See also: Sourcing CBD: Marijuana, Industrial Hemp & the Vagaries of Federal Law.)

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CBD News 9/3/2016

I’m Just Mad About Saffron (& other spices that activate the endocannabinoid system)

spices for endocannabinoid system
By on August 31, 2016

Modern science is starting to catch on to the wisdom of our ancestors, who knew a lot about using aromatic herbs and spices for medicinal purposes. The use of spices for cooking, healing and dyeing fabric has shaped much of human history. In ancient times these highly precious commodities were traded along well-traveled spice routes throughout Asia, the Middle East, Northern Africa and Europe. Some spices were literally worth their weight in gold.

Yet it’s only recently that scientists have discovered the bioactive constituents and molecular mechanisms of several common kitchen spices, which have been shown to reduce oxidative stress and inflammation while modulating multiple healing pathways simultaneously. A number of scientific studies confirm that the health-promoting properties of various spices are mediated by the same receptors in the human brain and body that respond pharmacologically to cannabis.

Saffron: Nerve Tonic

A 2013 report by Iranian scientists in Pharmacognosy Review examined the neuroprotective effects of saffron extracts, which inhibited the build-up of beta-amyloid plaque in the brain in animal models of Alzheimer’s. The same article noted that saffron extracts could “prevent retinal damage [and] age-related macular degeneration.” An Italian research team subsequently showed that saffron can counteract the effects of continuous bright light exposure in lab rats by enhancing retinal blood flow. Saffron “engages” both the CB1 cannabinoid receptor and the CB2 cannabinoid receptor “in order to afford retinal protection,” the Italian scientists concluded.

Described as “the most expensive cultivated herb in the world,” saffron (Crocus sativus) is a much-revered food seasoning and a natural colorant. Cultivated originally in Persia and Asia Minor, this legendary spice comes from a light purple flower with thread-like red-orange stigma that contains 150 bioactive components, including carotenoids, flavonoids, and other potent polyphenols. A rich source of riboflavin (vitamin B-2) and free-radical scavengers, saffron has a long history of use as a folk medicine for treating cancer, convulsions, headaches, skin conditions, asthma, ulcers, premenstrual distress, and other diseases. The Ebers papyrus (1550 BC) refers to saffron as a “cheering cardiac medicament” and a cure for kidney problems.

Scientific studies indicate that saffron improves learning and memory by inhibiting the breakdown of acetylcholine. Saffron also enhances the functioning of the GABA receptor, which explains in part its efficacy as relaxant and nerve tonic. Clinical trials evaluated the anti-depressant properties of saffron and concluded that it was more effective than a placebo and equivalent to Prozac.

Turmeric: Holy Powder

Turmeric (Curcuma longa), a perennial plant of the ginger family, has a safe 6,000-year track record as a medicinal herb, a culinary spice, and a dye for fabric and food. The fleshy rhizome of this all-star botanical is ground into a deep orange-yellow powder and used to season South Asian cuisine. It is a significant ingredient in most commercial curries, as well as a staple of Ayurvedic medical practice, which utilizes turmeric (typically in combination with other herbs) to treat indigestion, throat infections, metabolic dysfunction, common colds, and many other ailments. Known as “the holy powder of India,” turmeric is also applied topically as an antibacterial and antifungal remedy for skin sores and to clean wounds.

tumeric cannabinoid receptorsThe Food and Drug Administration, the perennial handmaiden of Big Pharma, recognizes turmeric as a food-coloring agent but not as a therapeutic substance, despite more than 5600 peer-reviewed studies of turmeric and its main polyphenolic component, curcumin, that document numerous healing attributes. There is more evidence-based scientific literature (1500 science articles) supporting the use of curcumin against cancer than any other nutrient, including vitamin D. Much like saffron, curcumin is a potent antioxidant that confers neuroprotective effects through multiple molecular channels. Turmeric protects against alcohol-induced brain damage, improves insulin sensitivity and cardiovascular function, inhibits platelet aggregation, and facilitates the clearing of beta-amyloid plaque associated with Alzheimer’s dementia. It's worth noting that the incidence of Alzheimer’s and other neurodegenerative diseases among people living in the Asian subcontinent, where turmeric is ubiquitous, is significantly lower than in North America.

Turmeric’s versatility as a medicinal herb derives in part from its interaction with the endocannabinoid system, which regulates numerous physiological processes. In May 2012, Neurochemical Research Identified the CB1 cannabinoid receptor as a mediator of curcumin’s antidepressant effect: “treatment with curcumin,” the report notes, “results in the sustained elevation . . . of endocannabinoids.” In December 2013, the European Journal of Pharmacology disclosed that curcumin reduces liver fibrosis by modulating cannabinoid receptor transmission.

Peppercorn: Black Gold

Employed since antiquity as both a food seasoning and a folk cure, black pepper (Piper nigrum) is the world’s most traded spice. Touted as “black gold,” the dried fruit of this woody vine -- the peppercorn -- was considered such a valuable commodity that it served as a substitute for money in business transactions. During the Middle Ages in Europe, black pepper was a luxury item only the wealthy could afford. Today, it is one of most commonly used spices on the planet.

The manifold therapeutic properties of black pepper have been validated by modern science. The essential oil of black pepper reduces nicotine cravings and eases withdrawal symptoms. An anti-spasmodic and anti-convulsant, it can also lower blood pressure and relieve digestive distress. Piperine, black pepper’s principal bioactive constituent, has been shown to inhibit cancer cell proliferation in animal models of osteosarcoma. In addition, this black pepper alkaloid potentiates the antitumoral and apoptotic effects of turmeric by enhancing the bioavailability of curcumin. When co-administered, piperine and curcumin interact synergistically to confer a stronger antidepressant effect than either compound delivers on its own.

In addition to piperine, black pepper contains vitamin K, iron and manganese along with a robust array of aromatic terpenes, which should be familiar to cannabis connoisseurs: pinene, limonene, linalool, sabinene . . . Black pepper is particularly well endowed with the sesquiterpene beta-caryophyllene, an important medicinal component of many cannabis strains. Beta-caryophyllene is the only terpene known to bind directly to CB2, the cannabinoid receptor that regulates immune function, the peripheral nervous system, metabolic tissue activity, and other physiological processes. Black pepper’s potent anti-inflammatory juju is mediated by the CB2 receptor. THC also binds directly to the CB2 receptor, although this is not what makes a person feel high when he or she consumes cannabis. That’s because CB2 receptors are not present to a significant degree in the brain and central nervous system.

Nutmeg: Cannabinoid Booster

Nutmeg (the dried kernel of Myristica fragrans) does not directly activate the CB1 cannabinoid receptor in the brain or the CB2 cannabinoid receptor in immune cells. But this commonly used kitchen spice can have a powerful impact on the endocannabinoid system. A study published earlier this year inPharmaceutical Biology reported that nutmeg interacts with the endocannabinoid system by inhibiting certain key enzymes that catabolize (break down) the two main endocannabinoids, anandamide and 2AG. Likened to the brain’s own marijuana, these short-lived endogenous cannabinoid compounds bind to the CB1 and CB2 receptors. This triggers a signaling cascade on a cellular level that protects neurons against toxic insults (stress) and promotes neurogenesis (the creation of new stem cells in adult mammals).

Two catabolic enzymes, fatty acid amide hydrolase (FAAH) and monoglycerol lipase (MAGL), are involved in the breakdown of anandamide and 2AG, respectively. Simply put, less FAAH and MAGL means more anandamide and 2AG. So by inhibiting these catabolic enzymes, nutmeg raises the level of anandamide and 2AG in the brain and boosts cannabinoid receptor signaling throughout the body. FAAH and MAGL inhibition has proven to be beneficial for easing pain, anxiety, hypertension and various inflammatory conditions in preclinical research, which lends credence to traditional medical uses of nutmeg.

Ayurvedic healers in India utilize nutmeg as an anxiolytic or anxiety-reducing agent. But there are conflicting accounts of nutmeg’s effect on anxiety and depression -- higher doses cause a biphasic response, exacerbating mood disorders and triggering hallucinations. Nutmeg has long been known for its central nervous system activity. In an article in Nature (1966), Alexander Shulgin identified “myristicin as a psychotropic substance.” Many prison inmates, including Malcolm X before his conversion to Islam, have sniffed and swallowed nutmeg to get high. Now we know how and why nutmeg has a psychoactive effect -- it stimuates cannabinoid receptor transmission by suppressing the enzymes that break down the brain's own marijuana.

Ecological medicine

Herbs and spices are ecological medicines. Seventy-five to ninety percent of the world’s rural people still rely on traditional plant medicine as their primary mode of health care. Numerous plants -- not just cannabis -- are endowed with compounds that interact directly or indirectly with the endocannabinoid system. The health benefits of many common kitchen spices are mediated by the same cannabinoid receptors in the human brain and body that marijuana activates.

Scientific research into marijuana’s effects on the brain has opened the door to whole new vistas of understanding human biology and physiology. As we welcome cannabis back into the pantheon of approved medicinal herbs, perhaps we should rethink our ideas about the endocannabinoid system, so named after the plant that led to its discovery, and stretch its boundaries to encompass an abundance of botanicals.

Martin A. Lee is the director of Project CBD and the author of Smoke Signals: A Social History of Marijuana -- Medical, Recreational and Scientific.


Selected Sources

  • Akhonzadeh S, et al, “Saffron in the treatment of patients with mild to moderate Alzheimer’s disease,” J Clini Parm Ther, 2010 Oct.
  • Bhutani, MK, et al, “Anti-depressant effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes,” Pharmocol Biochem Behav, 2009 March.
  • Cordell, Barbara  and Buckle, Jane, “The effects of aromatherapy on nicotine craving on a U.S. campus: a small comparison study.” J Altern Complement Med. 2013 July 31.
  • El-Alfy, Abir T, et al, “Indirect modulation of the endocannabinoid system by specific fractions of nutmeg total extract,” Pharmaceutical Biology, 2016.
  • Gertsch, J, et al, “Beta-caryophyllene is a dietary cannabinoid,” Proc Natl Acad Sci USA, 2008 July.
  • Gohari, Ahmad Reza, et al, “An overview on saffron, phytochemicals, and medicinal properties,” Pharmacogn Rev, 2013 Jan-Jun.
  • Hassan M, et al, “Pharmacological basis for the medicinal use of black pepper and piperine in gastrointestinal disorders,” Anticancer Res. 2009 Dec 01.
  • Hassanzadeh P, et al, “The CB1 receptor-mediated endocannabinoid signaling and NGF: the novel targets of curcumin,” Neurochemical Research, 2012 May.
  • Javadi, B, et al, “A Survey of Saffron in Major Islamic Traditional Medicine Books,” Iranian Journal of Basic Medical Sciences, 2013.
  • Ji, Sayer, “600 Reasons Turmeric May Be the World’s Most Important Herb,” GreenMedInfo.com, July 10, 2013.
  • Ji, Sayer, “Better than Chemo: Turmeric Kills Cancer Not Patients,” GreenMedInfo.com, Sept. 12, 2015.
  • Kannappan, Ramaswamy, et al, “Neuroprotection by Spice-Derived Nutraceuticals,” Molecular Neurobiology, 2011 October.
  • Kazem M, et al, “Antispasmodic effect of Piper nigrum fruit hot water extract on rat ileum,” Pak J Biol Sci, 2008 Jun 01.
  • Khazdair, Mohammad Reza, et al, “The effects of Crocus sativus (saffron) and its constituents on nervous system: A review,” Avicenna Journal of Phytomedicine, Sept-Oct 2015.
  • Khorasany, AR, et al, “Therapeutic effects of saffron (Crocus sativus L.) in digestive disorders: a review,” Iranian Journal of Basic Medical Sciences, 2016.
  • Mishra A, et al, “Anticonvulsant mechanisms of piperine, a piperidine alkaloid,” Channels (Austin). 2015 Sep 02.
  • Natoli, R, et al, “Gene and noncoding RNA regulation underlying photoreceptor protection: microarray study of dietary antioxidant saffron and photobiomodulation in rat retina,” Molecular Vision, 2016.
  • Patil, Vaishali M, et al, “Quantum Chemical and Docking Insights Into Bioavailability Enhancement of Curcumin by Piperine in Pepper,” J Phys Chem A, 2016 May 26.
  • Rapino, Cinzia, et al, “Type-1 and Type-2 Cannabinoid Receptor Signaling is Involved in the Neuroprotective Effect of Saffron of Rat Retina,” poster at International Cannabinoid Research Society conference, 2016 June.
  • Rose, J E and Behm FM, “Inhalation of vapor from black pepper extract reduces smoking withdrawal symptoms,” Drug Alcohol Depend. 1994 Feb 01.
  • Samarghandian, Saeed, et al, “Anticarcinogenic effect of saffron (crocus sativus L.) and its ingredients,” Pharmacognosy Res, 2014 Apr-Jun.
  • Zhang J, et al, “Piperine inhibits proliferation of human osteosarcoma cells via G2/M phase arrest and metastasis by suppressing MMP-2/-9 expression,” Int Immunopharmacol. 2014 Dec 31.
  • Zhang Z, et al, “Curcumin modulates cannabinoid receptors in liver fibrosis in vivo and inhibits extracellular matrix expression in hepatic stellate cells by suppressing cannabinoid receptor type-1 in vitro,” European Journal of Pharmacology, 2013 Dec 5.

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CBD News 8/25/2016

Clinical Endocannabinoid Deficiency Reconsidered

endocannabinoid tone russo
By on August 02, 2016

Abstract (Cannabis and Cannabinoid Research) 2016

Medicine continues to struggle in its approaches to numerous common subjective pain syndromes that lack objective signs and remain treatment resistant. Foremost among these are migraine, fibromyalgia, and irritable bowel syndrome, disorders that may overlap in their affected populations and whose sufferers have all endured the stigma of a psychosomatic label, as well as the failure of endless pharmacotherapeutic interventions with substandard benefit. The commonality in symptomatology in these conditions displaying hyperalgesia and central sensitization with possible common underlying pathophysiology suggests that a clinical endocannabinoid deficiency might characterize their origin. Its base hypothesis is that all humans have an underlying endocannabinoid tone that is a reflection of levels of the endocannabinoids, anandamide (arachidonylethanolamide), and 2-arachidonoylglycerol, their production, metabolism, and the relative abundance and state of cannabinoid receptors. Its theory is that in certain conditions, whether congenital or acquired, endocannabinoid tone becomes deficient and productive of pathophysiological syndromes. When first proposed in 2001 and subsequently, this theory was based on genetic overlap and comorbidity, patterns of symptomatology that could be mediated by the endocannabinoid system (ECS), and the fact that exogenous cannabinoid treatment frequently provided symptomatic benefit. However, objective proof and formal clinical trial data were lacking. Currently, however, statistically significant differences in cerebrospinal fluid anandamide levels have been documented in migraineurs, and advanced imaging studies have demonstrated ECS hypofunction in post-traumatic stress disorder. Additional studies have provided a firmer foundation for the theory, while clinical data have also produced evidence for decreased pain, improved sleep, and other benefits to cannabinoid treatment and adjunctive lifestyle approaches affecting the ECS.

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