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The Debate Continues

To Use Epilepsy How CBD for

newkhab
15.03.2019

Content:

  • To Use Epilepsy How CBD for
  • Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?
  • Frequently asked questions about cannabidiol (CBD) and children with epilepsy
  • For those adults treating with nonpsychoactive CBD, what dosage did you start with? Specifically for 22%/05% CBD/THC ratio with 22 mg dosage for pound . Jun 27, Galveston resident Trysten Pearson, who has epilepsy, experienced his . Texas patients must get two doctors to approve their use of CBD oil. May 17, Although CBD oil has become a trendy cure-all, treatment of epilepsy is the only use that has garnered significant scientific evidence.

    To Use Epilepsy How CBD for

    More information on this and other studies is available at http: No results of a randomized controlled trial are available yet. This type of research is the standard used to determine efficacy of medications. The breadth of applications has also expanded.

    CBD oils are now available in gels or patches as well as in oil form. Epidiolex, the medication being used in Dr. Sixteen physicians are participating in the study, but none of them are in Colorado. A randomized trial is now occurring to determine the efficacy of this product for children with epilepsy.

    Any child taking cannabis-related products should be closely monitored by a physician. Parents of children with severe, intractable epilepsy may understandably be tempted to take desperate measures.

    The most commonly reported side effects in the Epidiolex study have been drowsiness, diarrhea, and decreased appetite. Increased seizures and convulsions have occurred in a small number of cases. Long-term effects are an open question. Marijuana use in children has been shown to have negative effects on the brain, but we do not know whether treatments containing little or no THC will have any long-term side effects. That can be a challenge.

    No pharmaceutical-grade medical marijuana is available in Colorado. No FDA testing or oversight is required; the FDA has issued warning letters to some producers not in Colorado after testing their products and finding that they did not contain the CBD claimed on the label. Other growers and dispensaries may also claim to offer forms of marijuana that are high in CBD and low in THC, but parents cannot arrange for their own lab testing in Colorado, because marijuana testing labs are not permitted to test samples from private citizens.

    Overall, elevated aminotransferases levels occurred in 12 patients in the CBD group and one in the placebo group, all of whom were on concomitant valproate therapy. In the nine patients with raised aminotransferases who did not discontinued treatment, liver enzymes reverted to normal on continuation of therapy. Adverse events most commonly reported in the randomized double-bind placebo-controlled trial of CBD in comparison with placebo in patients with Dravet syndrome Overall, this trial provides for the first time robust evidence that CBD added-on to pre-existing AED treatment reduces the frequency of convulsive seizures in children and young adults with Dravet syndrome.

    Interestingly, no significant differences between groups were found in sleep scores, behavioral adaptation Vineland-II scores, and Quality of Life in Childhood Epilepsy scores, even though duration of treatment was relatively short and possibly insufficient to determine changes in these parameters.

    A major weakness in the presentation of the trial results is the failure to report changes in plasma concentrations of concomitant AEDs and, most notably, clobazam and N-desmethylclobazam. Two well controlled double-blind trials in patients with Lennox-Gastaut syndrome have been completed, but results to date have only been reported in summary form. Treatment-related serious adverse events were reported in nine CBD patients and one placebo patient.

    Elevations in transaminases occurred mostly in patients on concomitant valproate therapy and all resolved. Duration of the trial was 14 weeks 2-week titration and week maintenance.

    Total seizures were also significantly reduced in both CBD groups compared with placebo. Some elevations in transaminases were seen.

    Published reports, however, provide no information on concomitant therapies, and most notably whether, and to what extent, the clinical improvement on CBD therapy could be related to elevation in serum concentrations of other medications, most notably clobazam and N-desmethylclobazam. The interest in cannabis preparations in the treatment of epilepsies, particularly drug refractory childhood epilepsies, has skyrocketed in recent years.

    Marijuana and other cannabis products with moderate to high THC content utilized primarily for recreational purposes are generally unsuitable for this indication, not only because evidence for an anti-seizure activity of THC is equivocal and risk of seizure aggravation cannot be excluded, but also because THC is associated with many undesired effects, including addiction liability, psychiatric disorders, cognitive and motor impairment — and, possibly, also cardiovascular toxicity.

    Compared with THC, CBD shows a better defined anticonvulsant profile in animal models considered to be predictive of efficacy against focal and generalized seizures. Moreover, CBD is largely devoid of adverse psychoactive effects, and is considered to lack the abuse liability associated with THC-containing products. Improvement in seizure control, often associated with additional benefits on sleep and behaviour, have been reported in a sizeable proportion of cases, 87 but interpretation of these data is made difficult by the uncontrolled nature of the observations.

    Additionally, as discussed in this article, there are concerns about the quality and variability of many of the products used, 98 particularly because cannabis treatment is often initiated spontaneously by patients or caregivers without adequate medical supervision. Evidence concerning the potential anti-seizure efficacy of cannabinoids reached a turning point in the last 12 months, with the completion of the first high-quality placebo-controlled trials of a purified oil-based liquid CBD preparation in patients with Dravet syndrome and Lennox-Gastaut syndrome.

    Therefore there is now for the first time class 1 evidence that CBD improves seizure control when added on to other AEDs in patients with two difficult-to-treat epileptic encephalopathies. Available data, however, do not allow to conclude that CBD per se has anti-seizure activity.

    At least for the trial published in full, 85 a majority of patients were receiving concomitant clobazam therapy, and it is unclear whether the reported seizure benefits, as well as adverse effects, were related to a direct action of CBD, or were mediated by a previously described 5-fold elevation in plasma N-desmethylclobazam levels. For the two studies in Lennox-Gastaut syndrome, the proportion of patients on concomitant clobazam therapy was not reported, but it is likely to have been significant because clobazam is a frequently used comedication in patients with this syndrome.

    Clarification of the independent effects of CBD would require re-assessment of trial data for the subgroup of patients not comedicated with clobazam, or the conduction of further studies after excluding such patients or, alternatively, adjusting blindly clobazam dosages to maintain unaltered concentration of N-desmethylclobazam.

    Additional well controlled studies are also desirable to determine the potential value of CBD in other seizure types and epilepsy syndromes, including refractory focal epilepsies. One of the reasons for the utilization of cannabis products to have become so popular among patients and their caregivers is that these products are generally regarded as causing fewer adverse effects compared with traditional AEDs, partly out of the misperception that remedies derived from natural products are unlikely to be harmful.

    Although these results are encouraging, further studies are required to evaluate the safety profile of CBD and other cannabis products in greater detail, particularly after long-term exposure and whenever these products are used in subpopulations potentially at risk. Elevations of liver enzymes have been frequently observed, especially in patients comedicated with valproate, and although they were generally reversible, close observation for signs suggestive of hepatic toxicity is advisable.

    Nabiximols, an oromucosal spray formulation containing approximately equal amounts of THC and CBD, has been commercially available in several countries for a number of years and has a relatively extensive safety record. Unlike THC, CBD is not associated with the development of tolerance after repeated administration in various seizure models, and there is no evidence of a withdrawal syndrome developing after CBD discontinuation.

    These are exciting times for research in cannabinoids. After almost four millennia of their documented medical use in the treatment of seizure disorders, we are very close to obtaining conclusive evidence of their efficacy in some severe epilepsy syndromes. The era of evidence-based prescription of a cannabis product is within our sight.

    National Center for Biotechnology Information , U. Journal List J Epilepsy Res v. Published online Dec Emilio Perucca 1, 2. Author information Article notes Copyright and License information Disclaimer. Received Jul 11; Accepted Sep This article has been cited by other articles in PMC. Abstract The interest in cannabis-based products for the treatment of refractory epilepsy has skyrocketed in recent years.

    Cannabis, Cannabidiol, Epilepsy, Seizures, Review. Introduction The history of human use of the Cannabis plant goes back to the dawn of mankind. Open in a separate window. Chemistry and mechanisms of action The genus Cannabis refers to a flowering plant of which there are three main species, Cannabis sativa , Cannabis indica and Cannabis ruderalis.

    Table 1 A list of targets and actions reported for CBD based on results of studies in different experimental models and systems 24 — Pharmacological profile in experimental models of seizures and epilepsy Among the many active principles found in the cannabis plant, THC is the most widely investigated for its many actions, including its psychoactive effects and risks associated with overdose and abuse.

    CBD In preclinical studies, CBD has been found to be active in a variety of seizures models, including seizures induced by maximal electro-shock 39 — 41 and by pentylentetrazole in rats and mice, 42 — 44 audiogenic seizures in rats 45 and seizures induced by 3-mercaptopropionic acid, bicuculline, picrotoxin, cocaine and isoniazid but not strychnine in mice.

    Clinical evidence of efficacy and safety: Well controlled randomized trials The recent flurry of research focused on the potential usefulness of cannabinoids in epilepsy has resulted in the completion of three well controlled randomized trials, all of which evaluated a liquid proprietary oral formulation of CBD. Table 2 Adverse events most commonly reported in the randomized double-bind placebo-controlled trial of CBD in comparison with placebo in patients with Dravet syndrome Double-blind trials in Lennox-Gastaut syndrome Two well controlled double-blind trials in patients with Lennox-Gastaut syndrome have been completed, but results to date have only been reported in summary form.

    Conclusions and future perspectives The interest in cannabis preparations in the treatment of epilepsies, particularly drug refractory childhood epilepsies, has skyrocketed in recent years. Marijuana and the Cannabinoids. Friedman D, Sirven JI. Historical perspective on the medical use of cannabis for epilepsy: Phytochemical and genetic analyses of ancient cannabis from Central Asia.

    On the preparations of the Indian hemp, or Gunjah: Cannabis indica their effects on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases. Epilepsy and other chronic convulsive disorders. ElSohly M, Gul W. Constituents of cannabis sativa. Oxford University Press; The pharmacological basis of cannabis therapy for epilepsy. J Pharmacol Exp Ther. Marijuana, endocannabinoids, and epilepsy: Mechoulam R, Parker LA.

    The endocannabinoid system and the brain. Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection.

    Cannabinoids as hippocampal network administrators. Cannabis and endocannabinoid signaling in epilepsy. Weeding out bad waves: Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy. Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus.

    Dynamic changes of CB1-receptor expression in hippocampi of epileptic mice and humans. In vivo activation of endocannabinoid system in temporal lobe epilepsy with hippocampal sclerosis. Medical marijuana in neurology. Detyniecki K, Hirsch L. Marijuana use in epilepsy: Curr Neurol Neurosci Rep. Friedman D, Devinsky O.

    Cannabinoids in the treatment of epilepsy. N Engl J Med. Molecular targets for cannabidiol and its synthetic analogues: Inhibition of an equilibrative nucleoside transporter by cannabidiol: Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes.

    Voltage-gated sodium NaV channel blockade by plant cannabinoids does not confer anticonvulsant effects per se. Molecular targets of cannabidiol in neurological disorders.

    Gaston TE, Friedman D. Pharmacology of cannabinoids in the treatment of epilepsy. Cannabidiol in medical marijuana: Cannabidiol mellows out resurgent sodium current. Progress report on new antiepileptic drugs: Neurological disorders in medical use of cannabis: Effects of cannabidiol on behavioral seizures caused by convulsant drugs or current in mice.

    Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. Karler R, Turkanis SA. The cannabinoids as potential antiepileptics. Consroe P, Wolkin A. Cannabidiol--antiepileptic drug comparisons and interactions in experimentally induced seizures in rats. Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures.

    The influence of cannabidiol and delta 9-tetrahydrocannabinol on cobalt epilepsy in rats. Protective effects of cannabidiol against seizures and neuronal death in a rat model of mesial temporal lobe epilepsy. An electro-physiological analysis of the anticonvulsant action of cannabidiol on limbic seizures in conscious rats. Phytocannabinoids as novel therapeutic agents in CNS disorders. A critical review of the anti-psychotic effects of cannabidiol: Neural basis of anxiolytic effects of cannabidiol CBD in generalized social anxiety disorder: Walter L, Stella N.

    The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Neurological aspects of medical use of cannabidiol.

    Cannabidivarin is anticonvulsant in mouse and rat. Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. Molecular pharmacology of phytocannabinoids. Prog Chem Org Nat Prod. Pharmacokinetics and pharmacodynamics of cannabinoids. The current status of artisanal cannabis for the treatment of epilepsy in the United States. Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans.

    Single dose kinetics of cannabidiol in man. Eur J Clin Pharmacol. Identification of cytochrome P enzymes responsible for metabolism of cannabidiol by human liver microsomes. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: GW Pharma Ltd; [cited Jul 6]. Cannabidiol CBD in Dravet syndrome: Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Cannabidiol is a potent inhibitor of the catalytic activity of cytochrome P 2C Cannabinoids and cytochrome P interactions.

    Neuropsychiatric and general interactions of natural and synthetic cannabinoids with drugs of abuse and medicines. The utility of cannabidiol in the treatment of refractory epilepsy. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Complex pharmacology of natural cannabinoids: Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment.

    Does cannabidiol protect against adverse psychological effects of THC? Cannabidiol in patients with treatment-resistant epilepsy: Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. Cannabinoids in treatment-resistant epilepsy: Anticonvulsant nature of marihuana smoking.

    Complex partial seizure symptoms affected by marijuana abuse. A case report and review of the literature. Marijuana use in adults admitted to a Canadian epilepsy monitoring unit.

    Marijuana use and epilepsy: Marijuana use and the risk of new onset seizures. Trans Am Clin Climatol Assoc. Grand mal convulsions subsequent to marijuana use. Cannabis and other illicit drug use in epilepsy patients. The legal status of cannabis marijuana and cannabidiol CBD under U. Cannabinoid dose and label accuracy in edible medical cannabis products. Food and Drug Administration. Food and Drug Administration; [cited Jun 26].

    The health effects of cannabis and cannabinoids: National Academy Press;

    Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?

    May 24, How to use CBD oil to reduce seizures for people with seizures. Aug 9, A brand of cannabidiol (CBD) was approved in June for treatment of epilepsy by the United States Food and Drug Administration (FDA). Nov 1, Information about the use of cannabis oil for epilepsy to gain seizure control. The most well known are two cannabinoids: CBD - cannabidiol.

    Frequently asked questions about cannabidiol (CBD) and children with epilepsy



    Comments

    Pepel

    May 24, How to use CBD oil to reduce seizures for people with seizures.

    Ulema1

    Aug 9, A brand of cannabidiol (CBD) was approved in June for treatment of epilepsy by the United States Food and Drug Administration (FDA).

    valis92

    Nov 1, Information about the use of cannabis oil for epilepsy to gain seizure control. The most well known are two cannabinoids: CBD - cannabidiol.

    sany202

    Dec 6, NEW ORLEANS -- About one-third of patients who used cannabidiol it can occur with humans who use CBD to treat epilepsy, she added.

    ethon93

    Mar 13, Project CBD has created a beginner's guide for cannabidiol of seizures); and some children have worse seizures when they take CBD.

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