Regarding marijuana use in children, parents should be aware of changes in a child's behavior, although this may be difficult with teenagers. Parents should look for withdrawal, depression, fatigue, carelessness with grooming, hostility, and deteriorating relationships with family members and friends. In addition, changes in academic performance, increased absenteeism or truancy, lost interest in sports or other favorite activities, and changes in eating or sleeping habits could be related to drug use. However, these signs may also indicate problems other than use of drugs.
The leaves have a peculiar and diagnostic venation pattern that enables persons poorly familiar with the plant to distinguish a cannabis leaf from unrelated species that have confusingly similar leaves (see illustration). As is common in serrated leaves, each serration has a central vein extending to its tip. However, the serration vein originates from lower down the central vein of the leaflet, typically opposite to the position of, not the first notch down, but the next notch. This means that on its way from the midrib of the leaflet to the point of the serration, the vein serving the tip of the serration passes close by the intervening notch. Sometimes the vein will actually pass tangent to the notch, but often it will pass by at a small distance, and when that happens a spur vein (occasionally a pair of such spur veins) branches off and joins the leaf margin at the deepest point of the notch. This venation pattern varies slightly among varieties, but in general it enables one to tell Cannabis leaves from superficially similar leaves without difficulty and without special equipment. Tiny samples of Cannabis plants also can be identified with precision by microscopic examination of leaf cells and similar features, but that requires special expertise and equipment.[12]
Cannabis has held sacred status in several religions. It has been used in an entheogenic context – a chemical substance used in a religious, shamanic, or spiritual context[58] - in the Indian subcontinent since the Vedic period dating back to approximately 1500 BCE, but perhaps as far back as 2000 BCE. There are several references in Greek mythology to a powerful drug that eliminated anguish and sorrow. Herodotus wrote about early ceremonial practices by the Scythians, thought to have occurred from the 5th to 2nd century BCE. In modern culture the spiritual use of cannabis has been spread by the disciples of the Rastafari movement who use cannabis as a sacrament and as an aid to meditation. The earliest known reports regarding the sacred status of cannabis in the Indian subcontinent come from the Atharva Veda estimated to have been written sometime around 2000–1400 BCE.[59]
I Love this Product! I've spent thousands of dollars over the last thirty years on vitamins and natural products to help me with my ADHD. This is better than anything I've tried before. It's also a lot cheaper. I don't lose my temper like I used to. It has improved my marriage. It has calmed my gut. I am much more productive both at home and at work. I feel like a normal calm human being again! I haven't found any bad side effects. I am recommending it to family and friends. Thank You!
Cannabis is a generic term used to denote the several psychoactive preparations of the plant Cannabis sativa. The major psychoactive consituent in cannabis is ∆-9 tetrahydrocannabinol (THC). Compounds which are structurally similar to THC are referred to as cannabinoids. In addition, a number of recently identified compounds that differ structurally from cannabinoids nevertheless share many of their pharmacological properties. The Mexican term 'marijuana' is frequently used in referring to cannabis leaves or other crude plant material in many countries. The unpollinated female plants are called hashish. Cannabis oil (hashish oil) is a concentrate of cannabinoids obtained by solvent extraction of the crude plant material or of the resin.
While very few clinical trials have explored the pain-relieving effects of CBD oil, a report published in the Cochrane Database of Systematic Reviews in 2018 examined the use of a variety of cannabis-based medicines and found they might be of some benefit in the treatment of chronic neuropathic pain. A type of pain triggered by damage to the somatosensory system (i.e., the system responsible for processing sensory stimuli), neuropathic pain often occurs in people with conditions like diabetes and multiple sclerosis.
Way, John. It’s amazing how life can be running along great one day, you’re bothering no one, loving others, minding your own business, enjoying your work and then one crooked cop can railroad you. This cop who screwed me over–Robert Bifano– failed to arrest a suicidal AWOL soldier a few years ago and the guy went on to kill his wife and then shot himself. Bifano got sued for his ineptitude.
CBD oil alleviates physical pain and anxiety – both of which can have a negative impact on sleep. Additionally, CBD oil can actually prolong sleep for some, leading to more rest from night to night. Most medical experts agree that marijuana is not particularly beneficial for individuals with medical conditions and/or mental health disorders, as the THC can increase their symptoms; this makes CBD oil a good alternative option for people with the following sleep disorders and medical conditions.
Derived from the stalk and seed of cannabis (hemp) plants, cannabidiol (CBD) oil or CBD hemp oil is a natural botanical concentrate that is high in the compound CBD. Of the more than 85 cannabinoids so far identified in the cannabis plant, CBD is the second most common after tetrahydrocannabinol (THC). Unlike THC, CBD is non-psychotropic and therefore doesn’t cause a euphoric high.
The use of Cannabis as a mind-altering drug has been documented by archaeological finds in prehistoric societies in Eurasia and Africa.[85] The oldest written record of cannabis usage is the Greek historian Herodotus's reference to the central Eurasian Scythians taking cannabis steam baths.[86] His (c. 440 BCE) Histories records, "The Scythians, as I said, take some of this hemp-seed [presumably, flowers], and, creeping under the felt coverings, throw it upon the red-hot stones; immediately it smokes, and gives out such a vapour as no Grecian vapour-bath can exceed; the Scyths, delighted, shout for joy."[87] Classical Greeks and Romans were using cannabis, while in the Middle East, use spread throughout the Islamic empire to North Africa. In 1545, cannabis spread to the western hemisphere where Spaniards imported it to Chile for its use as fiber. In North America, cannabis, in the form of hemp, was grown for use in rope, clothing and paper.[88][89][90][91]
Medicinal claims are those which attribute to food the property of preventing, treating or curing a human disease. It is not permitted to make a medicinal claim about food. Therefore claims such as ‘treats seizures’, ‘cures cancer’, ‘lowers anxiety’ or ‘anti-inflammatory’ must not be made on the label of a food, verbally or on associated marketing material such as websites, social media, leaflets, etc.
Receptra offers their products in two separate lines. One is the Active Lifestyle range, which provides lower concentrations for daily use, and another is Health and Wellness, which is for far more intense use. It is incredibly difficult for me to manage my back pain with a low concentration of CBD usually, so, I went with the 3000 mg concentration available in their Health and Wellness line.    
Since 1929, Standard Process has been the visionary leader in whole food nutrient solutions. We apply systems thinking to holistic nutrition that empowers practitioners to transform lives. Dedicated to the whole food philosophy of our founder, Dr. Royal Lee, our goal is to carry on his mission to provide nutrients for the body that are as close as possible to how they are found in nature.
Results of a Phase III study (N = 177) comparing Sativex, THC-predominant extract and placebo in intractable pain due to cancer unresponsive to opiates (Johnson and Potts 2005) demonstrated that Sativex produced highly statistically significant improvements in analgesia (Table 1), while the THC-predominant extract failed to produce statistical demarcation from placebo, suggesting the presence of CBD in the Sativex preparation was crucial to attain significant pain relief.

The use of Cannabis as a mind-altering drug has been documented by archaeological finds in prehistoric societies in Eurasia and Africa.[85] The oldest written record of cannabis usage is the Greek historian Herodotus's reference to the central Eurasian Scythians taking cannabis steam baths.[86] His (c. 440 BCE) Histories records, "The Scythians, as I said, take some of this hemp-seed [presumably, flowers], and, creeping under the felt coverings, throw it upon the red-hot stones; immediately it smokes, and gives out such a vapour as no Grecian vapour-bath can exceed; the Scyths, delighted, shout for joy."[87] Classical Greeks and Romans were using cannabis, while in the Middle East, use spread throughout the Islamic empire to North Africa. In 1545, cannabis spread to the western hemisphere where Spaniards imported it to Chile for its use as fiber. In North America, cannabis, in the form of hemp, was grown for use in rope, clothing and paper.[88][89][90][91]
Yet another benefit of essential fatty acids is mood health. Several studies have shown that Omega 3 supplementation can improve symptoms in bipolar disorder. Others have found improvements in. This could be because essential fatty acids are critical to maintaining brain function.  Endocannabinoids are also essential for mood. The endocannabinoid system regulates the release of neurotransmitters, some of which play major roles in conditions like depression and anxiety. As mentioned previously, endocannabinoids are made from fat. Consuming extra essential fatty acids gives your body the ability to produce these lipids.
Szaflarski explains that cannabis contains about 500 different compounds, some of which—including CBD and THC—interact with certain chemical receptors in the human nervous system. But unlike THC, CBD isn’t psychoactive—meaning it doesn’t cause any kind of a high. Despite that, the US Drug Enforcement Agency classifies CBD (and other cannabis compounds) as schedule I substances, making their sale illegal in many states.

A limited number of studies have examined the effects of cannabis smoking on the respiratory system.[88] Chronic heavy marijuana smoking is associated with coughing, production of sputum, wheezing, and other symptoms of chronic bronchitis.[68] The available evidence does not support a causal relationship between cannabis use and chronic obstructive pulmonary disease.[89] Short-term use of cannabis is associated with bronchodilation.[90] Other side effects of cannabis use include cannabinoid hyperemesis syndrome.[91]
We use a combination of both Subcritical and Supercritical extractions. This allows us to perform a “fractional extraction” by first extracting at lower pressures to remove the lighter, temperature-sensitive volatile oils, and then subsequently extracting the same material at a higher pressure to remove the remaining oils. This approach is the best because it allows us to extract a complete range of cannabinoids, terpenes, essential oils, and other beneficial phytochemicals that yield a more potent blend.
Anecdotal evidence from patients is becoming increasingly widespread as well. Morgan Freeman suffers from pain and he was quoted saying, “I have fibromyalgia pain in my arm and the only thing that offers any relief is marijuana.” Whoopi Goldberg also uses cannabis to treat her daily pain from glaucoma and has even launched a line of medical cannabis products geared towards women suffering from menstrual pain.
Marijuana is the most popular illicit drug in the world, for no reason other than the fact that it produces a psychoactive chemical called tetrahydrocannabinol. Still, recreational marijuana use, which involves pursuing the euphoric sensations produced by cannabis consumption, is steadily becoming more and more legal, both in the United States and abroad.
Cannabis plants produce a unique family of terpeno-phenolic compounds called cannabinoids, some of which produce the "high" which may be experienced from consuming marijuana. There are 483 identifiable chemical constituents known to exist in the cannabis plant,[49] and at least 85 different cannabinoids have been isolated from the plant.[50] The two cannabinoids usually produced in greatest abundance are cannabidiol (CBD) and/or Δ9-tetrahydrocannabinol (THC), but only THC is psychoactive.[51] Since the early 1970s, Cannabis plants have been categorized by their chemical phenotype or "chemotype", based on the overall amount of THC produced, and on the ratio of THC to CBD.[52] Although overall cannabinoid production is influenced by environmental factors, the THC/CBD ratio is genetically determined and remains fixed throughout the life of a plant.[37] Non-drug plants produce relatively low levels of THC and high levels of CBD, while drug plants produce high levels of THC and low levels of CBD. When plants of these two chemotypes cross-pollinate, the plants in the first filial (F1) generation have an intermediate chemotype and produce intermedite amounts of CBD and THC. Female plants of this chemotype may produce enough THC to be utilized for drug production.[52][53]
However, the DEA has recently made many people nervous by talking about CBD restrictions. So how can people know if the CBD they acquire is legal? They simply have to check the source, and it’s clear sailing from there on out. For example, Medix CBD has CBD products that are legal across all fifty states, meaning that their products are always safe to use.
CBD (cannabidiol) oil is a popular product for everything from pain control to promoting sleep. However, with the rise of CBD comes the concern about failing a drug test due to detection of CBD oil. News stories are emerging across the country involving famous sports players, employees of companies, and others who have gotten positive drug screening results for the presence of THC—the psychoactive component of marijuana—even though CBD oil is said to be THC-free. 
^ Jump up to: a b c Whiting, PF; Wolff, RF; Deshpande, S; Di Nisio, M; Duffy, S; Hernandez, AV; Keurentjes, JC; Lang, S; Misso, K; Ryder, S; Schmidlkofer, S; Westwood, M; Kleijnen, J (23 June 2015). "Cannabinoids for Medical Use: A Systematic Review and Meta-analysis" (PDF). JAMA. 313 (24): 2456–2473. doi:10.1001/jama.2015.6358. hdl:10757/558499. PMID 26103030.
Cannabis is frequently used among Sufis[132] – the mystical interpretation of Islam that exerts strong influence over local Muslim practices in Bangladesh, India, Indonesia, Turkey, and Pakistan. Cannabis preparations are frequently used at Sufi festivals in those countries.[132] Pakistan's Shrine of Lal Shahbaz Qalandar in Sindh province is particularly renowned for the widespread use of cannabis at the shrine's celebrations, especially its annual Urs festival and Thursday evening dhamaal sessions - or meditative dancing sessions.[133][134]
Frequent questions have been raised as to whether psychoactive drugs may be adequately blinded (masked) in randomized clinical trials. Internal review and outside analysis have confirmed that blinding in Sativex spasticity studies has been effective (Clark and Altman 2006; Wright 2005). Sativex and its placebo are prepared to appear identical in taste and color. About half of clinical trial subjects reported previous cannabis exposure, but results of two studies (Rog et al 2005; Nurmikko et al 2007) support the fact that cannabis-experienced and naïve patients were identical in observed efficacy and adverse event reporting
CBD oil alleviates physical pain and anxiety – both of which can have a negative impact on sleep. Additionally, CBD oil can actually prolong sleep for some, leading to more rest from night to night. Most medical experts agree that marijuana is not particularly beneficial for individuals with medical conditions and/or mental health disorders, as the THC can increase their symptoms; this makes CBD oil a good alternative option for people with the following sleep disorders and medical conditions.
Discount Nutrition store operator Anthony LaBorde and owner Mona Baker discuss the CBD oil they sell at their stores in Midtown Atlanta and Acworth. Across Georgia, stores are selling cannabidiol to the public, while registered medical marijuana patients can’t legally buy low THC oil. BOB ANDRES /BANDRES@AJC.COM Photo: The Atlanta Journal-Constitution
Even though most manufacturers claim that CBD does not have any side effects, research says otherwise. Sure, most people can tolerate the impact of CBD just fine, but a small portion of the population have been noted to experience not-so-adverse side effects. According to Cannabis and Cannabinoid Research, the most common results are tiredness, change in weight, diarrhea, fatigue.
High-CBD strains tend to deliver very clear-headed, functional effects without the euphoric high associated with high-THC strains. They’re typically preferred by consumers who are extremely sensitive to the side effects of THC (e.g., anxiety, paranoia, dizziness). A high-CBD strain would also be a great choice for someone needing to medicate throughout the day to control pain, inflammation, anxiety, or other chronic conditions.
Whether the drug and non-drug, cultivated and wild types of Cannabis constitute a single, highly variable species, or the genus is polytypic with more than one species, has been a subject of debate for well over two centuries. This is a contentious issue because there is no universally accepted definition of a species.[54] One widely applied criterion for species recognition is that species are "groups of actually or potentially interbreeding natural populations which are reproductively isolated from other such groups."[55] Populations that are physiologically capable of interbreeding, but morphologically or genetically divergent and isolated by geography or ecology, are sometimes considered to be separate species.[55] Physiological barriers to reproduction are not known to occur within Cannabis, and plants from widely divergent sources are interfertile.[43] However, physical barriers to gene exchange (such as the Himalayan mountain range) might have enabled Cannabis gene pools to diverge before the onset of human intervention, resulting in speciation.[56] It remains controversial whether sufficient morphological and genetic divergence occurs within the genus as a result of geographical or ecological isolation to justify recognition of more than one species.[57][58][59]
While many states have now passed laws legalizing the production of plants bearing Cannabidiol for medicinal use, these laws will take many months if not years to be implemented while the details are ironed out as to whom will produce the plants and products for distribution in each of these states. Many patients and families in the states that have enacted these CBD laws are frustrated that they currently have no way to access CBD, in most cases assuming that Cannabidiol has to be extracted from illicit Marijuana oil. It has also been frustrating for patients and families that still find themselves in states with neither Medical Marijuana programs that provide access to Marijuana oil nor Cannabidiol laws providing access to CBD.

While only 9 states currently have legalized recreational marijuana, as an industry weed has had a huge year of growth. This is in large part due to the increasing popularity of products that contain CBD in them. CBD, short for cannabidiol, is one of the hundreds of compounds found in the cannabis plant, and the potential it has shown in helping with pain, seizures and anxiety have made it a natural fit for medical and recreational weed alike.
The legal problems occur once the extracts contain higher percentages of THC, or when they’re made from cannabis plants that are no longer considered “hemp” (so basically high THC plants). Products with these extracts might be in violation of the United States Controlled Substances Act (US CSA). This is when laws regarding specific states or countries will apply. 

Hey Justin, after further research and consultation it looks like the law is still a little unclear. According to NWTimes, CBD is now legal; however the law further clarifies that the CBD must contain certification that it contains less than 0.3% THC and is derived from industrial-hemp and not marijuana. That said, CBD from industrial hemp is legal for recreational usage, while CBD derived from marijuana is still viewed under the same laws as marijuana.… Read more »
Cannabis oil is produced by extracting the resin of the female cannabis plant using a solvent. After the resin is dissolved in the solvent, it is evaporated leaving a concentrated extract behind. What is left is an extract with THC and/or CBD, that can be blended with hemp seed oil, olive or other types of carrier oils to facilitate ingestion. Cannabis vape oils contain varying levels of THC and can knock out even the most experienced of smokers.

Scott Shannon, M.D., assistant clinical professor at the University of Colorado, recently sifted through patient charts from his four-doctor practice to document CBD’s effects on anxiety. His study, as yet unpublished, found “a fairly rapid decrease in anxiety scores that appears to persist for months,” he says. But he says he can’t discount a placebo effect, especially since “there’s a lot of hype right now.”


Various strains of "medical marijuana" are found to have a significant variation in the ratios of CBD-to-THC, and are known to contain other non-psychotropic cannabinoids.[61] Any psychoactive marijuana, regardless of its CBD content, is derived from the flower (or bud) of the genus Cannabis. Non-psychoactive hemp (also commonly-termed industrial hemp), regardless of its CBD content, is any part of the cannabis plant, whether growing or not, containing a ∆-9 tetrahydrocannabinol concentration of no more than 0.3% on a dry-weight basis.[62] Certain standards are required for legal growing, cultivating, and producing the hemp plant. The Colorado Industrial Hemp Program registers growers of industrial hemp and samples crops to verify that the dry-weight THC concentration does not exceed 0.3%.[62]
Since 1929, Standard Process has been the visionary leader in whole food nutrient solutions. We apply systems thinking to holistic nutrition that empowers practitioners to transform lives. Dedicated to the whole food philosophy of our founder, Dr. Royal Lee, our goal is to carry on his mission to provide nutrients for the body that are as close as possible to how they are found in nature.
CBD hemp oil has been proven in clinical trials to benefit humans and animals alike, as we both have endocannabinoid systems and are receptive to the chemical compound. Current studies also show that it is impossible to overdose on the substance. There is no need to worry if your dog takes a larger dose of CBD than anticipated – it is highly unlikely to have any negative effects, making it a safe and easy alternative treatment for your pet.
Cannabinoids may offer significant “side benefits” beyond analgesia. These include anti-emetic effects, well established with THC, but additionally demonstrated for CBD (Pertwee 2005), the ability of THC and CBD to produce apoptosis in malignant cells and inhibit cancer-induced angiogenesis (Kogan 2005; Ligresti et al 2006), as well as the neuroprotective antioxidant properties of the two substances (Hampson et al 1998), and improvements in symptomatic insomnia (Russo et al 2007). 

While research into the effects of CBD on specific conditions is important, a broader perspective on the relationship between CBD and the human body is necessary to understand how this unique compound works. Interestingly, many of the conditions that are supposedly helped by CBD have no well-understood cause, from acne to Alzheimer’s disease. However, one of the few common denominators between these conditions is the involvement of the endocannabinoid system (ECS) in their causes.
Yes, under licence from the Department of Health, certain varieties of the hemp plant (Cannabis sativa) are legally grown for a range of uses including for food and feed. The varieties of hemp permitted to be grown in Europe are those listed in the EU’s ‘Common Catalogue of Varieties of Agricultural Plant Species’ and for which the tetrahydrocannabinol (THC) content does not exceed 0.2% (Regulation (EU) No 1307/2013).
In states with medical cannabis laws, consumers should try to purchase cannabis from licensed suppliers who share their test results, which hopefully validate their products’ robust cannabinoid and terpenoid profiles. If you’re looking to purchase hemp through an online outlet, research your purchase beforehand to ensure that you aren’t being duped.

Cannabis is frequently used among Sufis[132] – the mystical interpretation of Islam that exerts strong influence over local Muslim practices in Bangladesh, India, Indonesia, Turkey, and Pakistan. Cannabis preparations are frequently used at Sufi festivals in those countries.[132] Pakistan's Shrine of Lal Shahbaz Qalandar in Sindh province is particularly renowned for the widespread use of cannabis at the shrine's celebrations, especially its annual Urs festival and Thursday evening dhamaal sessions - or meditative dancing sessions.[133][134]

Success stories like Oliver’s are everywhere, but there’s not a lot of data to back up those results. That’s because CBD comes from cannabis and, like nearly all other parts of the plant, is categorized by the Drug Enforcement Agency (DEA) as a Schedule 1 drug—the most restrictive classification. (Others on that list: heroin, Ecstasy, and peyote.) This classification, which cannabis advocates have tried for years to change, keeps cannabis-derived products, including CBD, from being properly studied in the U.S.


First of all, you need to know that CBD oil can come from both the hemp plant and from medical marijuana.  Both of those plants are different varieties of cannabis but they’re much different in the terms of chemical compounds they have.  Medical marijuana is good for people with certain ailments because it does contain the THC and it can contain any varying level of the THC or any varying level of CBD. 

Phytocannabinoids are the herbal, natural and classical cannabinoids found in the cannabis plant. The glandular structure called the trichomes is where the concentrated viscous resin of the plant is found. There are over 60 cannabinoids that have been isolated from the plant. Tetrahydracannabinol (THC), Cannabidiol (CBD) and Cannabinol (CBN) are the most prevalent ones and have also been the most studied. Cannabidiol (CBD) accounts for up to 40% of the plant’s extract. It has been widely reported that CBD offers the greatest possible benefits of any of the extracts found in the plant. CBD can also be derived from hemp. Hemp and cannabis both contain large amounts of natural CBD, but hemp is naturally low in THC; thus, making it easier for manufacturers to create high CBD-infused products with low to non-existent THC levels. Since THC is (mostly) still illegal in the United States, most CBD items we carry are derived from hemp. Each CBD product varies in the amount of CBD and THC levels found in the product. No items we carry are over the legal limit of THC levels, which is 0.3%, according to U.S. Federal Law.
When used as treatment for pain, CBD has a powerful effect on neuropathic pain, which is pain of the nerves and might be caused by peripheral nerve injury or other factors. By activating CB2 receptors, CBD activates many of the pathways that ease pain, and this goes a long way towards managing long term conditions such as diabetes, MS, and fibromyalgia.
“THC”—the more-famous, high-inducing compound in cannabis—“works directly on the cannabinoid system, meaning it attaches to receptors and mimics some of our own internal endocannabinoids,” says Igor Grant, a professor and chair of psychiatry at the University of California, San Diego School of Medicine. But CBD’s interaction with the endocannabinoid system is subtler. “Normally, these endocannabinoid-signaling molecules are broken down by enzymes, and one thing CBD does is interfere with the actions of those enzymes.”
Now, marijuana and hemp are both members of the cannabis family, so they do share a lot of characteristics. There is, however, a crucial difference between the two–the amount of psychoactive Tetrahydrocannabinol (THC) each plant produces. While marijuana can contain up to 30% THC, hemp contains no more than 0.3% THC. In other words, marijuana can get you really high, while hemp has such a low amount of THC, that it would be impossible to get high off it.
Going forward, another emerging trend among recreational users are wellness lifestyles built around cannabis. This is certainly part of the influence of California’s new recreational marijuana market, which went online January 1, 2018. California is already an epicenter for health and wellness lifestyles and fads. Expect to see more of the same now that cannabis is completely legal.
If your intention is to help treat chronic pain, then you may want to start out with a lower dose, and then proceed from there. If you notice effective results, you can downsize the dose, or likewise you can always up the dose until positive results are achieved. The key is to only increase your dosage in small increments so that you are able to pinpoint exactly how much CBD oil it takes to treat your condition. Be advised, though, that you should not exceed the recommended daily doses that are listed on the bottle and you should consult with a physician.
Thapa, D., Toguri, J. T., Szczesniak, A. M., & Kelly, A. E. M. (2017, April 1). The non-psychoactive phytocannabinoid, cannabidiol (CBD), and the synthetic derivatives, HU308 and CBD-DMH, reduces hyperalgesia and inflammation in a mouse model of corneal injury [Abstract]. FASEB Journal. Retrieved from https://www.fasebj.org/doi/abs/10.1096/fasebj.31.1_supplement.811.7
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