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"Cannabidiol: Barriers to Research and Potential Medical Benefits"

Mr. Chairman, Ms. Chairwoman, and Members of the Senate Drug Caucus, thank you for inviting the National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health (NIH), to participate in this hearing to share what we know about the biology and the potential therapeutic effects of cannabidiol (CBD), one of the main active chemical compounds found in marijuana. In light of the rapidly evolving interest in the potential use of marijuana and its derivative compounds for medical purposes, it is important to take stock of what we know and do not know about the therapeutic potential of CBD.

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Background

To date, 23 states and the District of Columbia have passed laws allowing marijuana to be used for a variety of medical conditions. Fifteen additional states have enacted laws intended to allow access to CBD oil and/or high-CBD strains of marijuana. Interest in the potential therapeutic effects of CBD has been growing rapidly, partially in response to media attention surrounding the use of CBD oil in young children with intractable seizure disorders including Dravet syndrome and Lennox-Gastaut syndrome. While there are promising preliminary data, the scientific literature is currently insufficient to either prove or disprove the efficacy and safety of CBD in patients with epilepsy.i and further clinical evaluation is warranted. In addition to epilepsy, the therapeutic potential of CBD is currently being explored for a number of indications including anxiety disorders, substance use disorders, schizophrenia, cancer, pain, inflammatory diseases and others. My testimony will provide an overview of what the science tells us about the therapeutic potential of CBD and of the ongoing research supported by NIH in this area.
CBD Biology and Therapeutic Rationale

CBD is one of more than 80 active cannabinoid chemicals in the marijuana plant.ii Unlike the main psychoactive cannabinoid in marijuana, tetrahydrocannabinol (THC), CBD does not produce euphoria or intoxication.iii,iv,v Cannabinoids have their effect mainly by interacting with specific receptors on cells in the brain and body: the CB1 receptor, found on neurons and glial cells in various parts of the brain, and the CB2 receptor, found mainly in the body’s immune system. The euphoric effects of THC are caused by its activation of CB1 receptors. CBD has a very low affinity for these receptors (100 fold less than THC) and when it binds it produces little to no effect. There is also growing evidence that CBD acts on other brain signaling systems, and that these actions may be important contributors to its therapeutic effects.ii
Preclinical and Clinical Evidence

Rigorous clinical studies are still needed to evaluate the clinical potential of CBD for specific conditions.i However, pre-clinical research (including both cell culture and animal models) has shown CBD to have a range of effects that may be therapeutically useful, including anti-seizure, antioxidant, neuroprotective, anti-inflammatory, analgesic, anti-tumor, anti-psychotic, and anti-anxiety properties.

Anti-Seizure Effects

A number of studies over the last two decades or more have reported that CBD has anti-seizure activity, reducing the severity of seizures in animal models.vi,vii In addition, there have been a number of case studies and anecdotal reports suggesting that CBD may be effective in treating children with drug-resistant epilepsy.viii,ix,x However, there have only been a few small randomized clinical trials examining the efficacy of CBD as a treatment for epilepsy; the total number of subjects enrolled in these studies was 48. Three of the four studies reported positive results, including decreased frequency of seizures. However, the studies suffered from significant design flaws, including failure to fully quantify baseline seizure frequency, inadequate statistical analysis, and a lack of sufficient detail to adequately evaluate and interpret the findings.viii Therefore, the currently available information is insufficient to draw firm conclusions regarding the efficacy of CBD as a treatment for epilepsy; a recent Cochrane review concluded, there is a need for “a series of properly designed, high quality, and adequately powered trials.”xi

NIDA is currently collaborating with the National Institute on Neurological Disorders and Stroke to evaluate CBD in animal models of epilepsy in order to understand the underlying mechanisms and optimize the conditions under which CBD may treat seizure disorders, and determine whether it works synergistically with other anti-seizure medications. In addition, clinical trials are currently underway by GW Pharmaceuticals, testing the efficacy of Epidiolex, a purified CBD extract, for treatment of pediatric epilepsy.

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Neuroprotective and Anti-Inflammatory Effects

CBD has also been shown to have neuroprotective properties in cell cultures as well as in animal models of several neurodegenerative diseases, including Alzheimer’s,xii,xiii,xiv stroke,xv glutamate toxicity,xvi multiple sclerosis (MS),xvii Parkinson’s disease,xviii and neurodegeneration caused by alcohol abuse.xix Nabiximols (trade name Sativex), which contains THC and CBD in roughly equal proportions, has been approved throughout most of Europe and in a number of other countries for the treatment of spasticity associated with MS. It has not been approved in the United States, but clinical trials are ongoing, and two recent studies reported that nabiximols reduced the severity of spasticity in MS patients.xx,xxi There have been limited clinical trials to assess the potential efficacy of CBD for the other indications highlighted; however, a recent small double-blind trial in patients with Parkinson’s disease found the CBD improved quality-of-life scores.xxii

Analgesic Effects

There have been multiple clinical trials demonstrating the efficacy of nabiximols on central and peripheral neuropathic pain, rheumatoid arthritis, and cancer pain.xxiii In addition, nabiximols is currently approved in Canada for the treatment of central neuropathic pain in MS and cancer pain unresponsive to opioid therapy. However, the current evidence suggests that the analgesia is mediated by THC and it is unclear whether CBD contributes to the therapeutic effects.xxiv THC alone has been shown to reduce pain;xxv,xxvi we are unaware of clinical studies that have explored the efficacy of CBD alone on pain. However, the anti-inflammatory properties of CBD (discussed above) could be predicted to play a role in the analgesic effects of nabiximols. Recent research has also suggested that cannabinoids and opioids have different mechanisms for reducing pain and that their effects may be additive, which suggests that combination therapies may be developed that may have reduced risks compared to current opioid therapies. However, this work is very preliminary.xxvii

Anti-Tumor Effects

In addition to the research on the use of cannabinoids in palliative treatments for cancer—reducing pain and nausea and in increasing appetite—there are also several pre-clinical reports showing anti-tumor effects of CBD in cell culture and in animal models.xxviii These studies have found reduced cell viability, increased cancer cell death, decreased tumor growth, and inhibition of metastasis (reviewed in McAllister et al, 2015).xxix These effects may be due to the antioxidant and anti-inflammatory effects of CBD;xxx however these findings have not yet been explored in human patients. There are multiple industry sponsored clinical trials underway to begin to test the efficacy of CBD in human cancer patients.

Anti-Psychotic Effects

Marijuana can produce acute psychotic episodes at high doses, and several studies have linked marijuana use to increased risk for chronic psychosis in individuals with specific genetic risk factors. Research suggests that these effects are mediated by THC, and it has been suggested that CBD may mitigate these effects.xxxi There have been a few small-scale clinical trials in which patients with psychotic symptoms were treated with CBD, including case reports of patients with schizophrenia that reported conflicting results; a small case study in patients with Parkinson’s disease with psychosis, which reported positive results; and one small randomized clinical trial reporting clinical improvement in patients with schizophrenia treated with CBD.xxxii Large randomized clinical trials would be needed to fully evaluate the therapeutic potential of CBD for patients with schizophrenia and other forms of psychosis.

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Anti-Anxiety Effects

CBD has shown therapeutic efficacy in a range of animal models of anxiety and stress, reducing both behavioral and physiological (e.g., heart rate) measures of stress and anxiety.xxxiii,xxxiv In addition, CBD has shown efficacy in small human laboratory and clinical trials. CBD reduced anxiety in patients with social anxiety subjected to a stressful public speaking task.xxxv In a laboratory protocol designed to model post-traumatic stress disorders, CBD improved “consolidation of extinction learning”, in other words, forgetting of traumatic memories.xxxvi The anxiety-reducing effects of CBD appear to be mediated by alterations in serotonin receptor 1a signaling, although the precise mechanism remains to be elucidated and more research is needed.xxxvii

Efficacy for Treating Substance Use Disorders

Early preclinical findings also suggest that CBD may have therapeutic value as a treatment of substance use disorders. CBD reduced the rewarding effects of morphinexxxviii and reduced cue-induced heroin seekingxxxix in animal models. A few small clinical trials have examined CBD and/or nabiximols (THC/CBD) for the treatment of substance use disorders; however, the available data are not sufficient to draw conclusions. NIDA is supporting multiple ongoing clinical trials in this area.

Safety of CBD

For reasons discussed previously, despite its molecular similarity to THC, CBD only interacts with cannabinoid receptors weakly at very high doses (100 times that of THC),xl and the alterations in thinking and perception caused by THC are not observed with CBD.iii.iv,v The different pharmacological properties of CBD give it a different safety profile from THC.

A review of 25 studies on the safety and efficacy of CBD did not identify significant side effects across a wide range of dosages, including acute and chronic dose regimens, using various modes of administration.xli CBD is present in nabiximols which, as noted earlier, is approved throughout most of Europe and in other countries. Because of this, there is extensive information available with regard to its metabolism, toxicology, and safety. However, additional safety testing among specific patient populations may be warranted should an application be made to the Food and Drug Administration.

Research Opportunities and Challenges

This is a critical area for new research. While there is preliminary evidence that CBD may have therapeutic value for a number of conditions, we need to be careful to not get ahead of the evidence. Ninety-five percent of drugs that move from promising preclinical findings to clinical research do not make it to market. The recently announced elimination of the PHS review of non-federally funded research protocols involving marijuana is an important first step to enhance conducting research on marijuana and its components such as CBD. Still, it is important to try to understand the reasons for the lack of well-controlled clinical trials of CBD including: the regulatory requirements associated with doing research with Schedule I substances, including a requirement to demonstrate institutional review board approval; and the lack of CBD that has been produced under the guidance of Current Good Manufacturing Processes (cGMP) – required for testing in human clinical trials – available for researchers. Furthermore, the opportunity to gather important information on clinical outcomes through practical (non-randomized) trials for patients using CBD products available in state marijuana dispensaries is complicated by the variable quality and purity of CBD from these sources.

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Ongoing CBD Research

The NIH recognizes the need for additional research on the therapeutic effects of CBD and other cannabinoids, and supports ongoing efforts to reduce barriers to research in this area. NIH is currently supporting a number of studies on the therapeutic effects as well as the health risks of cannabinoids. These include studies of the therapeutic value of CBD for:

Treatment of substance use disorders (opioids, alcohol, cannabis, methamphetamine)
Attenuation of the cognitive deficits caused by THC
Neuropathic pain due to spinal cord injury
Mitigating the impact of cannabis use on risk for schizophrenia
Examination of the potential of CBD as an antiepileptic treatment

It is important to note that NIDA’s mission is focused on drug abuse; studies related to the therapeutic effects of CBD in other areas would be funded by the Institute or Center responsible for that program area. For example, studies related to epilepsy will likely be funded by the National Institute of Neurological Disorders and Stroke or by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, while studies related to schizophrenia will likely be funded by the National Institute on Mental Health.
Conclusion

There is significant preliminary research supporting the potential therapeutic value of CBD, and while it is not yet sufficient to support drug approval, it highlights the need for rigorous clinical research in this area. There are barriers that should be addressed to facilitate more research in this area. We appreciate the opportunity to testify on the potential use of CBD for therapeutic purposes. Thank you again for inviting me here today, and I look forward to any questions you may have.

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Copyright © 2017 Natural Alchemist. All Rights Reserved.

* These statements have not been evaluated by the FDA. If you are pregnant, nursing, taking medications, or have a medical condition, consult your physician before using this product. Representations regarding the efficacy and safety of CBD have not been evaluated by the Food and Drug Administration. The FDA only evaluates foods and drugs, not supplements like these products. These products are not intended to diagnose, prevent, treat, or cure any disease. Click here to find evidence of a test, analysis, research, or study describing the benefits, performance or efficacy of CBD based on the expertise of relevant professionals.

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References

i Welty et al. Cannabidiol: promise and pitfalls. Epilepsy Curr. 14(5):250-2. (2014).
ii Borgelt et al. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy (Review) 33 (2): 195–209 (2013).
iii Martin-Santos et al. Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers. Curr Pharm Des. 2012;18(32):4966-79.
iv Fusar-Poli et al. Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing. Arch Gen Psychiatry. 2009;66(1):95-105.
v Winton-Brown et al. Modulation of Auditory and Visual Processing by Delta-9-Tetrahydrocannabinol and Cannabidiol: an fMRI Study. Neuropsychopharmacology. 2011 Jun;36(7):1340-8.
vi Jones et al. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. Seizure. 2012 Jun;21(5):344-52.
vii Consroe P and Wolkin A. Cannabidiol--antiepileptic drug comparisons and interactions in experimentally induced seizures in rats. J Pharmacol Exp Ther. 1977 Apr;201(1):26-32.
viii Porter BE and Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy & Behavior 29 (2013) 574–577.
ix Press et al. Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy. Epilepsy & Behavior 45 (2015) 49–52.
x Hussain et al. Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy Behav. 2015 Apr 29. pii: S1525-5050(15)00157-2.
xi Gloss and Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst Rev. 3:CD009270. (2014).
xii Esposito G et al. The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells. J Mol Med (Berl). 84(3):253-8. (2006).
xiii Martín-Moreno et al. Cannabidiol and Other Cannabinoids Reduce Microglial Activation In Vitro and In Vivo: Relevance to Alzheimer’s Disease. Molecular Pharmacology. 79(6):964-973. (2011).
xiv Iuvone et al.Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. J Neurochem. 89(1):134-41. (2004).
xv Pazos et al. Mechanisms of cannabidiol neuroprotection in hypoxic-ischemic newborn pigs:role of 5HT(1A) and CB2 receptors. Neuropharmacology. 71:282-91. (2013).
xvi Hampson et al. Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl AcadSci U S A.95(14):8268-73. (1998).
xvii Pryce et al. Neuroprotection inExperimental Autoimmune Encephalomyelitis and Progressive Multiple Sclerosis by Cannabis-Based Cannabinoids. J Neuroimmune Pharmacol. 2014 Dec 24. [Epub ahead of print]
xviii García-Arencibia et al. Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson's disease: importance of antioxidant and cannabinoid receptor-independent properties. Brain Res. 1134(1):162-70. (2007).
xix Hamelink et al. Comparison of cannabidiol, antioxidants, and diuretics in reversing binge ethanol-induced neurotoxicity. J Pharmacol Exp Ther. 2005 Aug;314(2):780-8.
xx Di Marzo and Centonze . Placebo effects in a multiple sclerosis spasticity enriched clinical trial with the oromucosal cannabinoid spray (THC/CBD): dimension and possible causes. CNS Neurosci Ther. 21(3):215-21. (2015).
xxi Flachenecker et al. Nabiximols (THC/CBD oromucosal spray,Sativex®) in clinical practice--results of a multicenter, non-interventional study (MOVE 2) in patients with multiple sclerosis spasticity. Eur Neurol.71(5-6):271-9. (2014)
xxii Chagas et al. Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial. J Psychopharmacol. 28(11):1088-98. (2014).
xxiii Russo EB. Cannabinoids in the management of difficult to treat pain. Therapeutics and Clinical Risk Management. 4(1):245-259.(2008).
xxiv Iskedjian et al. Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. Curr Med Res Opin. 23(1):17-24.(2007).
xxv Svendsen et al. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ. 2004 Jul 31;329(7460):253.
xxvi Portenoy et al. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain. 2012 May;13(5):438-49.
xxvii Neelakantan et al. Distinct interactions of cannabidiol and morphine in three nociceptive behavioral models in mice. Behav Pharmacol. 26(3):304-14. (2015).
xxviii McAllister et al. The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids. J Neuroimmune Pharmacol. 2015 Apr28. [Epub ahead of print]
xxix McAllister et al. The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids. J Neuroimmune Pharmacol. 2015 Apr28. [Epub ahead of print].
xxx Massi et al. 5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid. J Neurochem. 2008 Feb;104(4):1091-100.
xxxi Wilkinson et al. Impact of Cannabis Use on the Development of Psychotic Disorders. Curr Addict Rep. 2014 Jun 1;1(2):115-128.
xxxii Iseger and Bossong. A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophr Res. 162(1-3):153-61. (2015).
xxxiii Guimaraes et al. Antianxiety effect of cannabidiol in the elevated plus-maze. Psychopharmacology (Berl) 100:558–559 (1990).
xxxiv Lemos et al. Involvement of the prelimbic prefrontal cortex on cannabidiol-induced attenuation of contextual conditioned fear in rats. Behav Brain Res 207:105–111(2010).
xxxv Bergamaschi et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology 2011;36:1219–1226.
xxxvi Das et al. Cannabidiol enhances consolidation of explicit fear extinction in humans. Psychopharmacology (Berl). 2013 Apr;226(4):781-92.
xxxvii Campos et al. Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats. Psychopharmacology (Berl). 2013 Mar;226(1):13-24.
xxxviii Katsidoni et al. Cannabidiol inhibits the reward-facilitating effect of morphine: involvement of 5-HT1A receptors in the dorsal raphe nucleus. Addict Biol. 2013;18(2):286–96.
xxxix Ren et al. Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances. J Neurosci. 2009;29(47):14764–9.
xl Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br J Pharmacol. 2008 Jan; 153(2): 199–215.
xli Bergamaschi et al. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011 Sep 1;6(4):237-49.


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“The only thing that they said is, ‘We can’t tell you,’ ” Smith said. “I called three different times, and I got the same answer.”
It is useful to take the oil inside if there are such problems as insomnia, inflammatory processes, neurosis, kidney disease, cystitis, cough, rheumatism, boils, edema, digestive problems.

Indications for use: It is recommended for the care of dehydrated, tarnished, tired skin. To care for wrinkled skin (reduces, smoothes wrinkles), as well as for preventive skin care, prone to wrinkles. Especially recommended for dry, mature, fading or damaged skin. It is also recommended for the care of dry, brittle, excessively fluffy, dull, curly hair. Curative effect: Studies show that hemp oil, close in quality to flaxseed, does effectively work on health, supporting the cardiovascular, endocrine and immune systems in the norm. It is also used to create healing ointments and balms.
Tea made from hemp has no psychotropic effect, but it is an excellent painkiller. It also stimulates the appetite, improves digestion, helps with sleep disorders. It is important that hemp tea does not have the side effects that other cannabis products have. So, for example, after its use, there is no lethargy, apathy.

alternative medicine shop in downtown Mission in October, he called the Kansas attorney general with a seemingly simple question: Am I allowed to sell hemp oil?
Hemp seed is the main high-grade source of this element. In addition, hemp seeds contain pectins that protect the stomach and intestinal mucosa, neutralize putrefactive bacteria and restore the natural microflora.
Despite the legal risks, some in the Kansas City metro area are open and upfront about their products.

Sanders’ attorney, Sean Pickett, sent a letter to Koster’s office last August on behalf of Hodgson’s store, telling the state attorney general he was mistaken in his interpretation of Missouri law.
The problem of "pure" nutrition is especially acute for children. Their body is particularly sensitive to various gene implants, so the cannabis porridge for them is a very important nutrient. Do not be afraid for the health of the child - hemp grain does not contain kanabinol, but it contains a lot of rare and useful fats and microelements, not only for children, but also for adults. Besides all this, hemp porridge is very tasty and, most likely, is one of the main products ideally suited to humans, sent by nature itself.
More About Doc RobDr. Robert Silver DVM, MS, CVA achieved his lifetime goal of becoming a veterinarian when he graduated from Colorado State University's (CSU) College of Veterinary Medicine in 1982. In the 90s, after creating Boulder's Natural Animal, a Holistic Wellness Center, Dr. Silver established effective protocols for a number of serious, potentially life-threatening chronic diseases in dogs and cats, such as cancer, allergies, chronic pain, inflammatory bowel disease, Canine epilepsy, and behavior problems. Dr. Silver's has also designed nutritional and herbal formulas for RxVitamins for Pets and worked directly with pets who have been given cannabis and hemp by their owners to address a number of difficult conditions such as epilepsy, pain, cancer and behavior problems. Although retired from day-to-day practice, Dr. Silver still consults on difficult cases referred from veterinarians, and continues to work as Chief Medical Officer for RxVitamins for Pets.

But that’s exactly what has gotten CBD shops on that side of the state line in trouble in the past.
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Other species: Cannabis sativa var. Indica - Indian hemp, Cannabis ruderalis - Cannabis weed

But state regulators have raided CBD shops in places like Alaska and Texas.

The fruit of hemp is a round-egg-shaped nut, 2.5-4.4 in length and 1.5-3.5 mm in width. It consists of an outer fruit shell of dark or light gray color, an inner thin seed coat and an embryo. In the embryo there are cotyledons, embryonic stem, leaves and rootlets. The weight of 1000 cannabis seeds is 9-25 g.
He also said buyers may not be getting what they think they’re getting.
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Family: Cannabaceae (Hemp)Description: An annual herbaceous dioecious plant 30-180 cm high, with an erect branched stalk of 3 to 30 mm in thickness. The leaves at the bottom are opposite, from the top - regular, deeply¬palchatorazdelnye, with lanceolate large-toothed lobes. Male flowers on pedicels, five-membered, whitish-green, collected in a paniculate branchy inflorescence; Female - with a rudimentary flower bed, form a spicate inflorescence, sit in the sinuses of the upper leaves. Fruit - seed, hidden in a shell; It is usually called a hemp seed. Blossoms in June-July. Fruiting in August-September. The mass of 1000 seeds - 18-25 g. Hemp oil was one of the main in Russia and only in the XVIII-XIX centuries it was gradually replaced by sunflower. Seeds contain fatty oil (up to 40%), resin, vitamin K, choline, cholesterol, sugars, edestin, saponins.
Summary of Dr. Rob Silver's Book on Cannabis and CBD for Pets: As of the fall of 2016, 25 states and the District of Columbia allow for the medicinal use of marijuana prescribed by physicians, for human patients. Many pet owners in these states are wondering if it might also be helpful for their dogs or cats with intractable epilepsy, or cancer, or arthritis, anxiety, appetite, nausea and more. This book helps to answer those questions. It presents a balanced approach to understand how the herb cannabis works in the human and animal body, and what possible problems might arise with its use. The book very specifically advises pet owners how to avoid these problems, and still provide their pets with relief. The legalities of the use of medical marijuana in pets is discussed in this book, so pet owners can understand that no matter how much a veterinarian might want to help a patient be free from pain or suffering, because the Federal government has marijuana categorized as a Schedule One Controlled Substance, meaning that it has no recognized medical uses, it is illegal for a vet to prescribe it. They might lose their license if they did. This book does not advise pet owners who live in states where there is not medical marijuana for people to break the law and give their pets an illegal substance in their state.
"Cropped from the ground" hemp car Ford. One of Henry Ford's first cars worked entirely on cannabis fuel. His body was also constructed of hemp plastic, which was 10 times stronger than steel. Of course, after this, in 1937, hemp was outlawed because of the potentially dangerous impact that it could have had on many types of heavy industry of those times, including oil, plastic and paper giants. Imagine where we would be today if these power-hungry tyrants did not prohibit such amazing hemp biotechnology!
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AaronNem
 
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Postby AnthonySkina » Sun Sep 17, 2017 12:26 am

The mystery to outsiders of this business of gathering information and selling to payday loan companies on an online auction is bringing big money in to a somewhat quiet industry. They end up paying for something that they do not really need. It is an important channel for those business owners. I recommend you to get yourself immediately registered with any of the websites and earn some fast cash; even while continuing your studies or doing your daily household chores. For example, let's say that your credit history is too awful for you to get a regular personal loan. Now the time has come to say good bye to all your short term financial obstacles conveniently by simply taking help of same day cash advance. A? Online marketing is definitely an adventurous industry. In 1986, he authored and National Legal Publishing Company published the nation's first book on Buying and Selling Automobile Dealerships. Search the online loans for poor credit extensively in order to find competitive rates and affordable additional charges. It is a suitable solution for those who a bad credit history or those who need instant cash.
Emergencies present different challenges to people which all require a quick and decisive response to contain the emergency. This financial help can be accommodating source to crack urgent cash desires in completely convenient manner. This has eventually given birth to problems like bad credit home loans. It is beneficial to have the entire student loan history including any changes in the ownership of the loan because many banks buy and sell loans, and the loan can have many owners during its life. The banking process might take longer; sometimes the money will be ready for withdrawal in 2 to 3 days.
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It does not matter if you have a bad or good financial standing. Rather than considering risky financial options like overcharging credit cards or writing checks without sufficient funds, make the choice to contact professionals with experience matching borrowers with the right paycheck advance lenders. The interest in obtaining a payday loan has grown tremendously all over the world. So it's critical for a borrower to read the agreement ahead of time before committing to the student loan in question. In addition, you will be amazed at how many choices of companies you have. Interest on these loans is usually about 15% meaning that if you borrow $100. Online cash loans are an easy way to get cash for desperate situations for a person. This fact makes payday loans an industry on the fringes of society because many of them prey on the poorer elements of society.
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AnthonySkina
 
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Yes, of course if you had a little money to spend it would make things a little easier but money is not required to start. Make sure you're dealing with a "same country" lender. It is important to compare payday loans to save your time and money. All your lender wants from you is a steady job, permanent US residence, and a valid checking account. The economy is in a recession yet people continue spending. The rate of interest on the borrowed amount is higher than the other normal loans, as these loans are short-term in nature. But if you carry an impressive credit score then you can apply for more and lenders might unleash more loan amount without any objection. If you're looking for ways to get cash now then consider the following options:. To find a payday cash advance loan online, you can check a website that offers payday loans from various lenders. You could also try selling them online through e - Bay or Craigslist, just don't forget to make your item look interesting by being a bit creative.
They misuse their position by charging a high rate of interest from the money seekers. - the finance charge (or the interest rate charged);. By giving them your checking account number, they can do a direct deposit into your account if you are approved. same day Payday cash advance loans for people on benefits are becoming quite popular all over the world as they quite simply assist in dealing with instant financial crunches and crisis situations in a great way. Second contact your tax professional for a couple of reasons, such as knowing the effect of your tax situation but also as a sales tool as to the advantages to your potential buyers.
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Kennethwal
 
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Postby Robertunemo » Thu Sep 21, 2017 11:43 am

Wait for the decision, which usually takes less than a day, many times it would just take a couple of minutes. Chances are, a child whose parents are very successful, look up to his parents. But a careful and good online loan market research can avail you best loan deal at an inexpensive price without doing much struggle. The higher the value of the loan, the greater the interest to be paid. Most of the time they have a 24 hours turn around time as they understand your immediate need. Instant Lolly is a licensed UK payday loan broker with no fees - just a handy service to help you get the loans you need, when you need them. Some of the advantages associated with loan include provision of application process online. Since this option is not always available, their second option will always be filling a regular loan that has low interest or the secured loan.
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It will describe how the money is to be repaid, give the loan amount and outline the fees. Think it is easy - Way too many people think that marketing is easy, but it isn't. As you are well aware, in the economy nowadays, getting approved to receive a loan with a good fair interest rate is becoming very rare. This is because these websites are affiliated with multiple online lenders and they will provide you with the one that can offer you the best rate on your loan. If you know you will have the means to pay back the loan on your next payday, this could be your fasted and most expedient way to ease your cash flow distress. All loans of virtually every type typically come with charges. There are many reasons why one should consider taking public transportation rather than driving. Make sure to compare quotes and cash loan offers from various lenders, doing so you'll ensure the lowest rate possible and also avoid fraud. Concentrate on a specific niche market that you can become an expert on and go out of your way and offer different options for your customers. But if a proper research of the market is undertaken, borrower may find lenders offering the loans at competitive rates.
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The Lending Club offers a wedding loan where couples can borrow up to $35,000 for their wedding expenses. This can also mean it will be easier to pay back that loan on time. These kinds of bad credit fast cash loans are becoming more and more popular throughout this country, and they can provide you with quick cash but at a price. Those were the three things that most short term loan lenders require and must be careful in entering the information. His win here was the fifth PGA win of Justin Rose's career. The amount that you have received with quick loans can be perfectly utilized to carry off your number of short term needs and desires on time that may be like pay out education fees of your child, outstanding bank overdraft, credit card dues, unpaid telephone bill or small shopping bill, buy grocery for home, arrange a small child's birthday party, handling sudden medical expense and so forth. However, sometimes payday doesn't come round quickly enough and some expenses can't wait for payday to be paid. You can have much fun doing it too, and let us face it; every one of us enjoys finding bargains and saving money. Being the short term loan facility, these loans doesn't require credit check or pledging collateral. Instead of waiting for money to fall from the sky, people who need fast cash can turn to a trusted lender for instant approval on a same day payday loan.
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Robertunemo
 
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The lenders will not inquire about the way you are spending the money. You can do it with just a computer and an internet connection and you can stay at home while doing business too. Another highly 'non talked' about part of the private mortgage industry is the knowledge that the note holder can sell their note at any time at any time during the loan term instead of waiting years for the loan to mature. Do remember though that these are a short term solution and you should never use it in order to help with another debt problem. Typically, surgeries are costly especially if they're done for aesthetic purposes. When special needs arise or emergencies show up out of nowhere fast cash loans can be a financial saving grace. Grocery bills, household expenses, tuition fee of your child, celebrating small festive occasions can easily be fulfilled. Instant Lolly is a licensed UK payday loan broker with no fees - just a handy service to help you get the loans you need, when you need them. If you spend a while online you will see a lot of weird ideas that many people have come up with and tried but the problem with a lot of these ideas is they don't always work. The borrower then submits the application at lender's site for verification.
These things can happen to anybody at any time and that's why the lending business is very risky and must not be taken lightly. Fortunately, these loans are not as easily abused as other loans. Well, take my advice and get rid of those thoughts right now. One of the most proactive and simple way to acquire fast cash and repay your debts is to borrow payday loans online. It is for this reason that I typically would not even give these types of "loans" a second look.
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As you go through the comparison process, don't be surprised if getting the information you need takes time. I have thoroughly researched the internet for real work at home business. Keep in mind, that there's a standard procedure being observed by banks and financing institutions. Fill out a simple form and they will provide you with the steps necessary for obtaining the loan. Something that all newbie's are against is paying for traffic but that is how most big time affiliates are making money. Applying for the SBA Patriot Express Loan: The Loan Package. There is no need to "remember" the repayment - the lender typically takes care of everything. Apart from this, these loans do not require extensive paper work to perform before the approval.
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If you fail or miss to repay on time then additional fee would be charged upon that. Quicken Loans National tournament host Tiger Woods (2009, 2012) is tied with Justin Rose (2010, 2014) for the most wins in this event at two each. At one time or another in your life it will probably happen that you will come up short on cash between paydays. least and should also have a bank checking account in your name. Try to save 10% to 20 % from your salary and deposit it in a savings account. Utah Title Loans understand the need of title loans in your lives and therefore are always ready to provide you easy title loans with low. It can seem insignificant, but the position of the financial loan applied for can create a significant distinction to the chances of success. There is a system that you will need to use in order to make money with cell phone marketing. Most of the time, the amount approved for release of funds is dependent upon income. The estate agents guaranteed a sale, but said that he might have to wait for longer.
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This is fastest source of getting cash without any complexity and this will help you to meet all your surprise expenses before your payday. Here's a guide on how to calculate loan payments and how the lender applies them on your loan. It is also crucial that you decide exactly how much you need to borrow and if it can be paid before the next paycheck period. If getting highly credible backlinks was easy then everybody would be doing it, that is why search engines have made it where only the harder links are holding a lot of weight that way it isn't just up to the owner of the site to determine how popular and credible their site actually is. It's best to consider how you deal with your finances and how disciplined you will be in paying back a credit card cash advance or fast cash payday loans. Other loan payments are offered for those who enlist in the military and receive money towards college education tuition. Usually, before approving the loan amount, lenders usually ask for a post dated check containing the borrowed amount along with the fees. Don't just accept the first offer if you feel the rates is too high.
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TravisUnisy
 
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Der Audio Converter von MediaHuman ist ein kostenloses Programm für Mac OS X und Home windows. The sound board is designed to be easy: it does not have polyphonic capacity, cannot play MP3's (MP3 is patented and costs $ to license, so this board makes use of the same but not-patented OGG format, there's tons of free converters that may flip an MP3 into OGG), is not reprogrammable or scriptable, and you may't have another type of trigger type.
Man kann NUR ogg in andere Dateien convertieren... umso verwirrender, da man in der liste auch ogg auswählen kann und es hier bei den Bildern ebenso den Anschein macht, als könne man auch MP3s und andere in ogg umwandeln. Nun können Sie eine beliebige Datei per Drag&Drop in den TAC ziehen, um die in ein anderes Audioformat zu konvertieren. Das Programm cdparanoia 2 kann als Various konvertiere ogg in wav zu cdda2wav zum Auslesen von Musik-CDs verwendet werden. Die Reihenfolge der Bilder zur Umwandlung in eine PDF Datei kann wahlweise mit den Pfeilen oder per Drag and Drop geändert werden. In den allermeisten Fällen enthält eine WAV Datei dabei unkompimierte Rohdaten.
Lo que sucede es que el codificador OGG originalmente descartó datos de la pista, y cuando lo convertiste a MP3, el codificador MP3 (LAME) descartó más datos, por lo que pierdes calidad. WAV (abgekürztwav) ist ein von Windows eingesetztes Containerformat, dass die Musik unkomprimiert speichert und daher gewaltige Mengen an Festplattenplatz benötigt. Die Lautstärke lies sich so am besten anpassen und mit Audacity hab ichs dann anschließend wieder in OGG umgewandelt - klappt tremendous! Besonders bei höheren Bitraten(ab one hundred sixty kbps) stellt MPC andere Formate wie MP3 und OggVorbis klanglich in den Schatten. Es gibt aber auch einen Output Treiber pcm, der dazu dient, PCM (Wave) Files zu schreiben.
Je nach Einstellungen und ausgewählten Dateien begegnet Ihnen womöglich eine Warnung , nach der Sie vom Transcodieren, also dem Umwandeln von einem verlustbehafteten Format in ein anderes absehen sollten, die Sie mit einem Klick auf Ja ignorieren können. Du kannst oggdrop verwenden um ogg in wav zu konvertieren (ogg-dateien per drag-and-drop auf das kleine fenster ziehen) und diese dann mit CDexä. All Parameters are optional, however it's essential konvertiere ogg zu wav to specify a minimum of one Audio Source: mp3, ogg or wav. Erfahren Sie hier auf alles zum Thema Computer Hardware Komponenten und über aktuelle Software. Der OGG MP3 Converter ermöglicht Ihnen, Audiospure für die Output Audio Datei zu wählen. Jetzt können Sie Audiotitel direkt in Ihrem Browser umwandeln: schnell, sicher und kostenlos. Benuzen Sie eine der Hinzufügen-Flächen um die zu konvertierenden Dateien auszuwählen, oder ziehen Sie diese einfach auf die weiße Fläche.
Sie können diese Software zum Kopieren der Materialien benutzen, wenn das Urheberrecht bei Ihnen liegt oder Sie eine Kopiergenehmigung vom Urheberrechtsinhaber erhalten haben. Es gibt einige zusätzliche Einstellungen der Audio-Konvertierung, damit Sie professionelle Ergebnisse zu erzielen. Bei der verlustfreien Kompression bleiben die Originaldaten erhalten, sie werden nur kompakter in eine Datei geschrieben. Ab diesem Second haben Sie die Möglichkeit die Datei WAV anhand aller Programme zu öffnen, die Sie hier finden. Auch zum Auslesen von Audio-CDs müssen Sie nicht additional ein grafisches Programm bemühen.
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Financial Institution Loans

Postby AndrewSpoxy » Sun Sep 24, 2017 5:51 pm

The RBI has a view that if loans are costlier, real estate prices will come down. Some payday lenders specialise in offering 7 day loans - these types of loans are typically lower in value e. The lender will deposit the check on the agreed upon date for reimbursement. It is true that starting an online business is much simpler but you can be misled by a number of over hyped offers and myths that abound on the internet, especially if you are a beginner. This is the main reason why Americans need access to fast cash. Essentially, the branch manager is the last stop for customer complaints and services, allowing customers to fix issues that personal bankers are not allowed to fix or refuse to fix, while providing lending overrides and denials in certain cases. But it really is frequently the most significant preserve up is obtaining docs despatched piece-meal, or not awareness what exactly is at this time becoming requested of you. If you are not interested in making yourself an object of gossip, it is best to stay away from this option.
If a divorce occurs, the student loan debt could be determined as a common debt to be shared if the couple lives in a common property state. Hence, with the help of these loans you can smartly remove mid month fiscal worries from your life in a decent way. When you have the right skills and someone showing you.
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Shop around until you find the lender offering the best rates and terms that suit your needs. Anyone can simply apply for such loans through online medium. A bus pass is considerably less expensive, and while it requires a bit of lifestyle adjustment, it is ultimately easier on your wallet. Due to the advent of the internet, getting loans through many online lenders is very easy. Choosing to use long-term credit as a finance option increases the likelihood of accumulating credit balances that will take months or years to pay down. What you need to know is that you must use your website in order to help your friends learn about something they might be interested in. Once you sign up for the program, you will be involving yourself with a series of steps which includes sorting through their online database which gives you a list of people that will pay you to sign up for specific offers. As soon as you find an outworker that has served other people successfully, you can let go of expensive staff.
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Free One Hour Loans
And the account that the card draws from can't be overdrawn-meaning no overdraft fees. They are a cash advance that gives the borrower the opportunity to take the loan interest free. Really the best place to look for these types of lenders is on the internet. This too is eliminated by the Depository Services India. With the right lender you can get all of the cash that you need in a very short period of time. Do you need extra money to sort out your fiscal problems. Just go for it, if you are confronting a financial emergency. People whoare considering applying for additional loans often get worried because of theformalities that come along with the process of applying for loan.
Payday Loans In Washington State
Payday Advance Harlingen
2 trillion dollars in federal student loans at a rate of 3. Some companies are equipped to give 1 hour payday loans. Take a look at this and see how easy it is to make your dream come true. Just a year from now, you could be making $400 a day, or about $100,000 a week. These times vary from county to county because certain counties have greater budget than others. They are sometimes also known as quick cash advances, and are very short-term loans, which involve petty amounts of money. The following will allow you to get cash quickly but will likely take a bit longer than the foregoing alternatives:. Payday loans and logbook loans are both loan types that are growing in popularity, yet not many people fully understand exactly how they work. You must be at least 18 years of age at the time of the application. It does not matter if you have a bad or good financial standing.
Loan Packages
Online Payday Loans In Usa
Payday Loans More Than One
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