Cannabidiol partially blocks the sleepiness in hypocretin-deficient rats. Preliminary data.

Image result for CNS Neurol Disord Drug Targets.“Excessive daytime sleepiness and cataplexy are among the symptoms of narcolepsy, a sleep disorder caused by the loss of hypocretin/orexin (HCRT/OX) neurons placed into the hypothalamus (LH). Several treatments for managing narcolepsy include diverse drugs to induce alertness, such as antidepressants, amphetamine, or modafinil, etc.

Recent evidence has shown that cannabidiol (CBD), a non-psychotropic derived from Cannabis sativa, shows positive therapeutic effects in neurodegenerative disorders, including Parkinson´s disease. Furthermore, CBD provokes alertness and enhances wake-related neurochemicals in laboratory animals. Thus, it is plausible to hypothesize that excessive somnolence observed in narcolepsy could be blocked by CBD.

Here, we determined whether systemic injection of CBD (5mg/Kg, i.p.) would block the sleepiness in a narcolepsy model.

Hourly analysis of sleep data showed that CBD blocked the sleepiness during the lights-off period across 7h post-injection in lesioned rats.

Taking together, these findings suggest that CBD might prevent sleepiness in narcolepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/31642794

Cannabidiol and Cannabinoid Compounds as Potential Strategies for Treating Parkinson’s Disease and L-DOPA-Induced Dyskinesia.

 “Parkinson’s disease (PD) and L-DOPA-induced dyskinesia (LID) are motor disorders with significant impact on the patient’s quality of life. Unfortunately, pharmacological treatments that improve these disorders without causing severe side effects are not yet available. Delay in initiating L-DOPA is no longer recommended as LID development is a function of disease duration rather than cumulative L-DOPA exposure.

Manipulation of the endocannabinoid system could be a promising therapy to control PD and LID symptoms.

In this way, phytocannabinoids and synthetic cannabinoids, such as cannabidiol (CBD), the principal non-psychotomimetic constituent of the Cannabis sativa plant, have received considerable attention in the last decade.

In this review, we present clinical and preclinical evidence suggesting CBD and other cannabinoids have therapeutic effects in PD and LID. Here, we discuss CBD pharmacology, as well as its neuroprotective effects and those of other cannabinoids.

Finally, we discuss the modulation of several pro- or anti-inflammatory factors as possible mechanisms responsible for the therapeutic/neuroprotective potential of Cannabis-derived/cannabinoid synthetic compounds in motor disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31637586

https://link.springer.com/article/10.1007%2Fs12640-019-00109-8

Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats.

animals-logo “The use of CBD-rich hemp products is becoming popular among pet owners with no long-term safety data related to consumption in adult dogs and cats.

The purpose of this study was to determine the single-dose oral pharmacokinetics of CBD, and to provide a preliminary assessment of safety and adverse effects during 12-week administration using a hemp-based product in healthy dogs and cats.

Serum chemistry and CBC results showed no clinically significant alterations, however one cat showed a persistent rise in alanine aminotransferase (ALT) above the reference range for the duration of the trial.

In healthy dogs and cats, an oral CBD-rich hemp supplement administered every 12 h was not detrimental based on CBC or biochemistry values.

Cats do appear to absorb or eliminate CBD differently than dogs, showing lower serum concentrations and adverse effects of excessive licking and head-shaking during oil administration.”

https://www.ncbi.nlm.nih.gov/pubmed/31635105

https://www.mdpi.com/2076-2615/9/10/832

Cannabidiol As A Novel Therapeutic Strategy For Oral Inflammatory Diseases: A Review Of Current Knowledge And Future Perspectives.

Image result for altern ther health med “The high frequency and painful profile of inflammatory oral lesions and the lack of an effective drug protocol for their management stimulate the search for pharmacological alternatives for the treatment of these conditions. Cannabidiol is the major non-psychotropic constituent of Cannabis sativa, receiving lately scientific interest because of its potential in the treatment of inflammatory disorders such as asthma, colitis and arthritis. There is little published in the current literature about the use of cannabidiol in oral health. Among its many protective functions, the ability to attenuate inflammation through the modulation of cytokines and its antiedema and analgesic effects may be important features in the treatment of oral lesions. In this review, we suggest that cannabidiol can be useful in the management of oral inflammatory disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31634872

Hemp seed polysaccharides protect intestinal epithelial cells from hydrogen peroxide-induced oxidative stress.

International Journal of Biological Macromolecules“The purpose of this study was to investigate structure of Hemp seed polysaccharide (HSP) and the protective effect of HSP from H2O2-induced oxidative damage in IPEC-1 cells and the possible mechanism of this protection.

Analysis of monosaccharide composition and structure of two fractions HSP0 and HSP0.2 from polysaccharide of Hemp seed (HSPc) were analyzed by high performance liquid chromatography (HPLC) and Fourier transform infrared spectroscopy (FT-IR).

The results showed that both HSP0 and HSP0.2 contain sulfate groups, which are sulfated polysaccharides. In IPEC-1 cells model, the release of LDH and MDA was significantly decreased, and the activities of SOD, GSH-Px and CAT were significantly increased in HSP0 and HSP0.2-treated group. HSP0.2 dramatically increased the gene expression of antioxidant enzymes and phase II detoxification enzymes measured by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In addition, HSP0.2 up-regulated the expression level of intracellular transcription factor Nuclear factor erythroid-2-related factor 2 (Nrf2) and inhibited the level of Kelch-like ECH-associated protein 1 (Keap1) with Western blot analysis.

Collectively, the present study suggested that HSP0.2 has the protective effect of IPEC-1 cells against H2O2-induecd oxidative stress. This protection mechanism may be related to activation of the Keap1/Nrf2 signaling pathway.”

https://www.ncbi.nlm.nih.gov/pubmed/31108145

https://www.sciencedirect.com/science/article/pii/S0141813018372660?via%3Dihub

Hemp seed pill may improve chronic constipation of the elderly and reduce the burden of helpers.

Logo of jfammpc“Chronic constipation is common but serious problem of the elderly.

Hemp seed pills had been used over 1000 years as a purgative in the traditional Chinese medicine, and moreover, had the data of double-blinded randomized control trial.

Japan Geriatric Society introduced hemp seed pill as one of choice for chronic constipation of elderly in their guideline.

Hemp seed pills might improve chronic constipation of elderly and reduce the burden of nursing stuffs.

Traditional Chinese medicine Hemp seed pill (麻子仁丸) could improve chronic constipation of elderly in the difficult case.”

https://www.ncbi.nlm.nih.gov/pubmed/31334198

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618208/

Kinetics of acetylcholinesterase inhibition by hemp seed protein-derived peptides.

Journal of Food Biochemistry banner“The aim of this work was to enhance the acetylcholinesterase (AChE)-inhibitory activity of a pepsin-produced hemp seed protein hydrolysates (HPH) through reverse-phase HPLC separation followed by identification of peptide sequences present in the most active fraction. The HPH was separated into eight fractions (F1-F8) with F7 exhibiting significantly (p < 0.05) the strongest (97.5%) in vitro inhibition of electric eel AChE (eeAChE) activity in comparison to 53.8% for HPH. The HPH consisted mostly of low molecular weight peptides of < 11 amino acid residues and most contained at least one hydrophobic amino acid. Kinetics of enzyme inhibition revealed a mixed-type inhibition of eeAChE activity by HPH whereas F7 acted through an uncompetitive mode; in contrast inhibition of human AChE by HPH and F7 was uncompetitive. The stronger inhibitory potency of the F7 peptides fraction against both enzymes was confirmed through reduced maximal velocity, catalytic efficiency, and inhibition constant values when compared to the HPH.

PRACTICAL APPLICATIONS: The use of natural products for the prevention or treatment of human diseases continues to be an area of intense research activities. Food protein-derived peptides obtained through enzymatic hydrolysis of hemp seed proteins were shown in vitro to be strong inhibitors of activities of both the eel and human forms of acetylcholinesterase (AChE). AChE is an important therapeutic target because excessive activity of this enzyme is a causative factor of neurodegenerative diseases such as dementia and Alzheimer’s. This work showed that peptides in the most active fraction are small in sizes, which may favor their absorption into blood circulation and possible permeation of the blood-brain barrier. Therefore, the hemp seed peptides are potential agents that can be used to formulate functional foods and nutraceuticals against neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/31353736

https://onlinelibrary.wiley.com/doi/abs/10.1111/jfbc.12897

Effect οf Genotype and Growing Year on the Nutritional, Phytochemical, and Antioxidant Properties of Industrial Hemp (Cannabis sativa L.) Seeds.

antioxidants-logo “Cannabis sativa L. seeds have been an important source of protein, oil, and dietary fiber for human and animals. Currently, there is a growing interest in the commercial products of these seeds, which are recognized as a legitimate source of medicaments, cosmeceuticals, and nutraceuticals.

The objective of this study was to investigate the nutritional, phytochemical composition, and antioxidant properties of seeds from seven hemp cultivars grown in Greece for three consecutive years.

All the measured parameters strongly varied under the influence of growing year and genotype. In particular, protein, oil, and carbohydrates’ content of hemp seeds as well as fatty acids’ composition were mainly affected by genotype, whereas the growing year had a major effect on phytochemical components and antioxidant activity, which was determined by the 2,2′-azino-bis (3-ethylbenzthiazoline sulfonate) (ABTS) and ferric-reducing antioxidant power (FRAP) assays. Moreover, a predominant effect of the year was observed for phenolic profiles as determined by high-performance liquid chromatography and total carotenoids’ content.

This study suggests that hemp seeds could be a promising food crop as a result of their high nutritive traits and antioxidant potential. A comparison of the studied cultivars, showed that Finola seeds had the highest oil and protein contents and, thus, appeared to be the most promising cultivar for cultivation in Greece.”

https://www.ncbi.nlm.nih.gov/pubmed/31627349

https://www.mdpi.com/2076-3921/8/10/491

Hemp seed/evening primrose oil affects expression of STAT3, IL-17, and FOXP3+ in experimental autoimmune encephalomyelitis.

Research in Pharmaceutical Sciences“T helper (Th)-17 mediate inflammation in both peripheral tissues and the central nervous system. Signal transducer and activator of transcription factor3 (STAT3) is required for Th-cell pathogenicity and its activation in the brain has been demonstrated during the acute phase of experimental autoimmune encephalomyelitis (EAE) through the mammalian target of rapamycin (mTOR) signaling. Rapamycin (RAPA), an inhibitor of mTOR, can drive Forkhead box P3 (FOXP3+) induction as a regulatory factor.

The aim of this study was to determine the effects of hemp seed/evening primrose oils (HSO/EPO) supplement on the expression of FOXP3+, STAT3, and interleukin (IL)-17 genes in EAE lymph nodes.

EAE was induced by myelin oligodendrocyte glycoprotein peptide in mice, and then the mice were assigned to three treatment groups compared to two control groups (EAE and naive). The histological findings of the spinal cord were evaluated. To determine the expression of FOXP3+, STAT3, and IL-17 genes in the lymphocytes, qRT-PCR was used.

Our results showed that EAE severity was reduced in HSO/EPO mice by reducing the expression of STAT3 and IL-17 genes and increasing the expression of FOXP3+ gene, which was confirmed by slight inflammation in the spinal cord. Histological findings showed a significant improvement in the HSO/EPO group.

Our findings suggest that the HSO/EPO treatment can be used to ameliorate the demyelination of spinal cord, which was confirmed by immunological and histological findings.”

https://www.ncbi.nlm.nih.gov/pubmed/31620191

http://www.rpsjournal.net/article.asp?issn=1735-5362;year=2019;volume=14;issue=2;spage=146;epage=154;aulast=Rezapour%2DFirouzi

Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions.

Epilepsia banner“Cannabidiol (CBD) has been approved by the US Food and Drug Administration (FDA) to treat intractable childhood epilepsies, such as Dravet syndrome and Lennox-Gastaut syndrome. However, the intrinsic anticonvulsant activity of CBD has been questioned due to a pharmacokinetic interaction between CBD and a first-line medication, clobazam. This recognized interaction has led to speculation that the anticonvulsant efficacy of CBD may simply reflect CBD augmenting clobazam exposure. The present study aimed to address the nature of the interaction between CBD and clobazam.

RESULTS:

CBD potently inhibited CYP3A4 mediated metabolism of clobazam and CYP2C19 mediated metabolism of N-CLB. Combination CBD-clobazam treatment resulted in greater anticonvulsant efficacy in Scn1a+/- mice, but only when an anticonvulsant dose of CBD was used. It is important to note that a sub-anticonvulsant dose of CBD did not promote greater anticonvulsant effects despite increasing plasma clobazam concentrations. In addition, we delineated a novel pharmacodynamic mechanism where CBD and clobazam together enhanced inhibitory GABAA receptor activation.

SIGNIFICANCE:

Our study highlights the involvement of both pharmacodynamic and pharmacokinetic interactions between CBD and clobazam that may contribute to its efficacy in Dravet syndrome.”

https://www.ncbi.nlm.nih.gov/pubmed/31625159

“Our results here suggest a novel benefit of CBD and clobazam combination therapy on premature death, a devastating aspect of the Dravet syndrome phenotype.”

https://onlinelibrary.wiley.com/doi/full/10.1111/epi.16355