Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome

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“BACKGROUND

The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome.

METHODS

In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment. The primary end point was the change in convulsive-seizure frequency over a 14-week treatment period, as compared with a 4-week baseline period.

RESULTS

The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, −22.8 percentage points; 95% confidence interval [CI], −41.1 to −5.4; P=0.01). The percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). The patient’s overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P=0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group.

CONCLUSIONS

Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375.)”

http://www.nejm.org/doi/10.1056/NEJMoa1611618

“Cannabinoids for Epilepsy — Real Data, at Last”  http://www.nejm.org/doi/full/10.1056/NEJMe1702205

“Cannabidiol (CBD) Significantly Reduces Convulsive Seizure Frequency in Dravet Syndrome (DS): Results of a Multi-center, Randomized, Double-blind, Placebo-controlled Trial (GWPCARE1)” http://files.shareholder.com/downloads/AMDA-1TW341/201889199x0x919787/73B57FA6-CD45-4ABB-8C89-87EFEA36B4ED/1332B_AES_Poster_Dravet_Part_B_.pdf

“EPILEPSY AND MARIJUANA: CANNABIS DRUG REDUCES DRAVET SYNDROME SEIZURES IN LARGE-SCALE CLINICAL TRIAL” http://www.newsweek.com/cannabis-marijuana-dravet-syndrome-epilepsy-clinical-trial-614982

“Study proves medicinal cannabis can help children with severe epilepsy, researchers say” http://www.abc.net.au/news/2017-05-25/scientific-study-medicinal-cannabis-helps-children-with-epilepsy/8556180
 

Cannabis as medicine

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“Evidence supports reform to allow the legitimate study, regulation, and prescription of therapeutic cannabinoids.hemp

From its first recorded uses in China through to the early 20th century, cannabis has had a place in the pharmacopoeia. Queen Victoria’s personal physician, Russel Reynolds, opined in the Lancet in 1890, “Indian hemp, when pure and administered carefully, is one of the most valuable medicines we possess.” This opinion was based on current best evidence: the careful and documented observation of its effects in medical conditions.

In a similar vein, calls have been made to reconsider the role of cannabis in today’s society. Two well informed British politicians recently told The BMJ, “We have heard striking testimonies from patients… that cannabis has ‘given them their life back.’” Added to this, the international position on cannabis as a potential medication has changed, with international agencies and many governments relaxing a prohibitionist stance.”

http://www.bmj.com/content/357/bmj.j2130

Short-Term Efficacy of CBD-Enriched Hemp Oil in Girls with Dysautonomic Syndrome after Human Papillomavirus Vaccination.

“Cannabidiol (CBD)-based treatments for several diseases, including Tourette’s syndrome, multiple sclerosis, epilepsy, movement disorders and glaucoma, are proving to be beneficial and the scientific clinical background of the drug is continuously evolving.

OBJECTIVES:

To investigate the short-term effect of CBD-enriched hemp oil for relieving symptoms and improving the life quality (QOL) in young girls with adverse drug effects (ADRs) following human papillomavirus (HPV) vaccine.

METHODS:

In this anecdotal, retrospective, “compassionate-use”, observational, open-label study, 12 females (age 12-24 years) with severe somatoform and dysautonomic syndrome following HPV vaccination were given sublingual CBD-rich hemp oil drops, 25 mg/kg per day supplemented by 2-5 mg/ml CBD once a week until a maximum dose of 150 mg/ml CBD per day was reached over a 3 month period. Patients’ quality of life was evaluated using the medical outcome short-form health survey questionnaire (SF-36).

RESULTS:

Two patients dropped out due to iatrogenic adverse events and another two patients stopped the treatment early due to lack of any improvement. SF-36 showed significant benefits in the physical component score (P < 0.02), vitality (P < 0.03) and social role functioning (P < 0.02) after the treatment. The administration of hemp oil also significantly reduced body pain according to the SF-36 assessment. No significant differences from the start of treatment to several months post-treatment were detected in role limitations due to emotional reactions (P = 0.02).

CONCLUSIONS:

This study demonstrated the safety and tolerability of CBD-rich hemp oil and the primary efficacy endpoint. Randomized controlled trials are warranted to characterize the safety profile and efficacy of this compound.”

https://www.ncbi.nlm.nih.gov/pubmed/28457055

“This study demonstrated the safety and tolerability of CBD-rich hemp oil and the primary efficacy endpoint” https://www.ima.org.il/imaj/viewarticle.aspx?year=2017&month=02&page=79

Medical Marijuana Laws May Be Associated With A Decline In The Number Of Prescriptions For Medicaid Enrollees

Health Affairs

“In the past twenty years, twenty-eight states and the District of Columbia have passed some form of medical marijuana law. Using quarterly data on all fee-for-service Medicaid prescriptions in the period 2007–14, we tested the association between those laws and the average number of prescriptions filled by Medicaid beneficiaries. We found that the use of prescription drugs in fee-for-service Medicaid was lower in states with medical marijuana laws than in states without such laws in five of the nine broad clinical areas we studied. If all states had had a medical marijuana law in 2014, we estimated that total savings for fee-for-service Medicaid could have been $1.01 billion. These results are similar to those in a previous study we conducted, regarding the effects of medical marijuana laws on the number of prescriptions within the Medicare population. Together, the studies suggest that in states with such laws, Medicaid and Medicare beneficiaries will fill fewer prescriptions.”      https://www.healthaffairs.org/doi/abs/10.1377/hlthaff.2016.1135?journalCode=hlthaff

“Medical Marijuana Laws Reduce Prescription Medication Use In Medicare Part D” https://www.healthaffairs.org/doi/abs/10.1377/hlthaff.2015.1661

“US states that allow medical marijuana see drop in prescriptions for other drugs, study finds. American states that allow patients access to medical marijuana are seeing fewer prescriptions per doctor for pharmaceutical drugs in several disease categories where marijuana is a potential treatment, a study in Health Affairs has found.” http://www.bmj.com/content/354/bmj.i3942.full

Antibacterial Properties of Hemp and Other Natural Fibre Plants: A Review

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“Intervention against pathogenic bacteria using natural plant material has a long history. Plant materials also have been widely used as fillers and/or reinforcers in polymer composites. Some natural fibre plants, such as hemp, are regarded to possess antibacterial activity against a wide range of pathogenic bacteria. Innovative applications can be explored if they are incorporated in polymer composites. This review aims to compile the relevant investigations on antibacterial activity of hemp and other fibre plants such as jute, flax, kenaf, sisal, and bamboo. The antibacterial character might be contributed from cannabinoids, alkaloids, other bioactive compounds, or phenolic compounds of lignin. This review is intended to encourage utilization of hemp and other natural fibre plants in value-added diversified products. Some potential applications are also discussed.” https://www.researchgate.net/publication/270502952_Antibacterial_Properties_of_Hemp_and_Other_Natural_Fibre_Plants_A_Review
“Antibacterial Properties of Hemp and Other Natural Fibre Plants: A Review”  http://ojs.cnr.ncsu.edu/index.php/BioRes/article/view/BioRes_09_2_Khan_Antibacterial_Hemp_Fibre_Review

Terpene synthases from Cannabis sativa.

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“Cannabis (Cannabis sativa) plants produce and accumulate a terpene-rich resin in glandular trichomes, which are abundant on the surface of the female inflorescence.

Bouquets of different monoterpenes and sesquiterpenes are important components of cannabis resin as they define some of the unique organoleptic properties and may also influence medicinal qualities of different cannabis strains and varieties.

Transcriptome analysis of trichomes of the cannabis hemp variety ‘Finola’ revealed sequences of all stages of terpene biosynthesis. Nine cannabis terpene synthases (CsTPS) were identified in subfamilies TPS-a and TPS-b.

Functional characterization identified mono- and sesqui-TPS, whose products collectively comprise most of the terpenes of ‘Finola’ resin, including major compounds such as β-myrcene, (E)-β-ocimene, (-)-limonene, (+)-α-pinene, β-caryophyllene, and α-humulene.

Transcripts associated with terpene biosynthesis are highly expressed in trichomes compared to non-resin producing tissues. Knowledge of the CsTPS gene family may offer opportunities for selection and improvement of terpene profiles of interest in different cannabis strains and varieties.”

https://www.ncbi.nlm.nih.gov/pubmed/28355238

Flexible Bionanocomposites from Epoxidised Hemp Seed Oil Thermosetting Resin Reinforced with Halloysite Nanotubes.

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“Hempseed (Cannabis sativa L.) oil comprises a variety of beneficial unsaturated triglycerides with well-documented nutritional and health benefits.

However, it can become rancid over a relatively short time period leading to increased industrial costs and waste of a valuable product. The development of sustainable polymers is presented as a strategy where both the presence of unsaturation and perox-ide content could be affectively utilised to alleviate both this waste and financial burden.

After reaction with peroxyacetic acid, incorporation of halloysite nanotubes (HNTs) and sub-sequent thermal curing, without the need for organic sol-vents or interfacial modifiers, flexible transparent materials with a low glass transition temperature were developed. The improvement in thermal stability and both the static and dynamic mechanical properties of the bionanocomposites were significantly enhanced with the well-dispersed HNT filler. At an optimum concentration of 0.5 wt.% HNTs, a simultaneous increase in stiffness, strength, ductility and toughness was observed in comparison to the unfilled cured resin.

These sustainable food-waste derived bionanocompo-sites may provide an interesting alternative to petroleum-based materials, particularly for low-load bearing applica-tions, such as packaging.”

https://www.ncbi.nlm.nih.gov/pubmed/28240903

Acetylcholinesterase inhibitors in Alzheimer’s disease

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“Alzheimer’s Disease (AD) is the most common single cause of dementia in our ageing society. On full assessment and diagnosis of AD, initiation of an AChe inhibitor is recommended as early as possible, it is important that AChe inhibitor therapy is considered for patients with mild to moderate AD.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014378/

“Characterization of Lignanamides from Hemp (Cannabis sativa L.) Seed and Their Antioxidant and Acetylcholinesterase Inhibitory Activities. Hempseed is known for its content in fatty acids, proteins and fiber, which contribute to its nutritional value. Lignanamides 2, 7, 9-14 showed good antioxidant activity among which 7, 10 and 13 also inhibited acetylcholinesterase in vitro. The new identified compounds in this study added to the diversity of hempseed composition and the bioassays implied that hempseed, with lignanamides as nutrients, may be a good source of bioactive and protective compounds.” http://www.ncbi.nlm.nih.gov/pubmed/26585089

“The Effects of Hempseed Meal Intake and Linoleic Acid on Drosophila Models of Neurodegenerative Diseases and Hypercholesterolemia. Our results indicate that hempseed meal (HSM) and linoleic acid are potential candidates for the treatment of Alzheimer’s disease (AD) and cardiovascular disease. These results show that HSM may prove of great utility as a health food, with potential for the prevention of AD and cardiovascular disease.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933972/

Accelerated Burn Wound Closure in Mice with a New Formula Based on Traditional Medicine.

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“A combination of the oils of sesame, hemp, wild pistachio, and walnut has been used for treatment of skin disorders, including wound burns, in some parts of Kerman, Iran. Evaluation of this remedy in the form of a pharmaceutical formulation in animal models can pave the way for its future application in wound burn healing in humans.

This experimental study investigated the healing potential of a new formula (NF) based on folk medicine from Iran for the treatment of third degree burns in mice. The formula was a combination of the oils of four plants: sesame (Sesamum indicum L.), wild pistachio (Pistacia atlantica Desf.), hemp (Cannabis sativa L.), and walnut (Juglans regia L.).

When compared to the controls, NF significantly improved wound contraction after day 10. Histopathological and immunohistochemical findings confirmed the efficacy of the NF.

CONCLUSIONS:

A new therapeutic remedy was introduced for the treatment of burn wounds.

Further clinical and molecular studies are suggested to determine the exact mechanism(s) involved in the burn wound healing effect of NF.”

https://www.ncbi.nlm.nih.gov/pubmed/28191338

Molecular Targets of the Phytocannabinoids: A Complex Picture.

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“For centuries, hashish and marihuana, both derived from the Indian hemp Cannabis sativa L., have been used for their medicinal, as well as, their psychotropic effects.

These effects are associated with the phytocannabinoids which are oxygen containing C21 aromatic hydrocarbons found in Cannabis sativa L.

To date, over 120 phytocannabinoids have been isolated from Cannabis.

For many years, it was assumed that the beneficial effects of the phytocannabinoids were mediated by the cannabinoid receptors, CB1 and CB2. However, today we know that the picture is much more complex, with the same phytocannabinoid acting at multiple targets.

This contribution focuses on the molecular pharmacology of the phytocannabinoids, including Δ9-THC and CBD, from the prospective of the targets at which these important compounds act.”