Characterization of endocannabinoids and related acylethanolamides in the synovial fluid of dogs with osteoarthritis: a pilot study.

Posted on November 8, 2017 by David Worrell

“Cannabis-based drugs have been shown to be effective in inflammatory diseases.

A number of endocannabinoids including N- arachidonoylethanolamide (anandamide, AEA) and 2-arachidonyl glycerol (2-AG) with activity at the cannabinoidreceptors (CBR) CBR1 and CBR2, have been identified. Other structurally related endogenous fatty acid compounds such as oleoylethanolamide (OEA) and palmitoyl ethanolamide (PEA) have been identified in biological tissues.

These compounds do not bind to CBR but might be involved in facilitating the actions of directly acting endocannabinoids and thus are commonly termed “entourage” compounds due to their ability to modulate the endocannabinoid system.

The aim of this study was to evaluate the presence of endocannabinoids and entourage compounds in the synovial fluid of dogs with osteoarthritis subjected to arthrotomy of the knee joint. Cytokines and cytology were studied as well.

AEA, 2-AG, OEA and PEA were all present in the synovial fluid of arthritic knees and in the contralateral joints; in addition, a significant increase of OEA and 2AG levels were noted in SF from OA knees when compared to the contralateral joints.

The identification and quantification of endocannabinoids and entourage compounds levels in synovial fluids from dogs with OA of the knee is reported for the first time. Our data are instrumental for future studies involving a greater number of dogs. Cannabinoids represent an emerging and innovative pharmacological tool for the treatment of OA and further studies are warranted to evaluate the effectiveness of cannabinoids in veterinary medicine.”

https://www.ncbi.nlm.nih.gov/pubmed/29110674

“The ECS can be exploited as a potential therapeutic option for OA. We have demonstrated the presence of AEA, 2-AG, OEA and PEA in the SF of dogs with OA. Our data open the avenue to future studies involving a higher number of dogs and aimed at defining the role played by these compounds in OA of the dogs. Both plant-derived and synthetic agonists of CBRs represent an emerging and innovative pharmacological tool for the treatment of OA. ” https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-017-1245-7

A review of methods for the chemical characterization of cannabis natural products.

Posted on October 11, 2017 by David Worrell

Journal of Separation Science

“Cannabis has garnered a great deal of new attention in the past couple of years in the United States due to the increasing instances of its legalization for recreational use and indications for medicinal benefit.

Despite a growing number of laboratories focused on cannabis analysis, the separation science literature pertaining to the determination of cannabis natural products is still in its infancy despite the plant having been utilized by humans for nearly 30 000 years and it being now the most widely used drug world-wide. This is largely attributable to the restrictions associated with cannabis as it is characterized as a Schedule 1 drug in the United States.

Presented here are reviewed analytical methods for the determination of cannabinoids (primarily) and terpenes (secondarily), the primary natural products of interest in cannabis plants. Focus is placed foremost on analyses from plant extracts and the various instrumentation and techniques that are used, but some coverage is also given to analysis of cannabinoid metabolites found in biological fluids. The goal of this work is to provide a collection of relevant separation science information, upon which the field of cannabis analysis can continue to grow.”

https://www.ncbi.nlm.nih.gov/pubmed/28986974

http://onlinelibrary.wiley.com/doi/10.1002/jssc.201701003/abstract

Potential of plant-sourced phenols for inflammatory bowel disease.

Posted on October 11, 2017 by David Worrell

“Inflammatory bowel disease (IBD) is an uncontrolled chronic inflammatory intestinal disorder, which requires medications for long-term therapy. Facing the challenges of severe side effects and drug resistance of conventional medications, to develop the strategies meet the stringent safety and effectiveness in the long-term treatment are urgent in the clinics.

In this regard, a growing body of evidence confirms plant-sourced phenols, such as flavonoids, catechins, stilbenes, coumarins, quinones, lignans, phenylethanoids, cannabinoid phenols, tannins, phenolic acids and hydroxyphenols, exert potent protective benefits with fewer undesirable effects in conditions of acute or chronic intestinal inflammation through improvement of colonic oxidative and pro-inflammatory status, preservation of the epithelial barrier function and modulation of gut microbiota.

In this review, the great potential of plant-sourced phenols and their action mechanisms for the treatment or prevention of IBD in recent research are summarized, which may help the further development of new preventive/adjuvant regimens for IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/28990509

http://www.eurekaselect.com/156267/article

Cannabis and Cannabinoids for Chronic Pain.

Posted on October 9, 2017 by David Worrell

Current Rheumatology Reports

“The purpose of this study was to provide the most up-to-date scientific evidence of the potential analgesic effects, or lack thereof, of the marijuana plant (cannabis) or cannabinoids, and of safety or tolerability of their long-term use.

RECENT FINDINGS:

We found that inhaled (smoked or vaporized) cannabis is consistently effective in reducing chronic non-cancer pain.

Oral cannabinoids seem to improve some aspects of chronic pain (sleep and general quality of life), or cancer chronic pain, but they do not seem effective in acute postoperative pain, abdominal chronic pain, or rheumatoid pain.

The available literature shows that inhaled cannabis seems to be more tolerable and predictable than oral cannabinoids. Cannabis or cannabinoids are not universally effective for pain. Continued research on cannabis constituents and improving bioavailability for oral cannabinoids is needed. Other aspects of pain management in patients using cannabis require further open discussion: concomitant opioid use, medical vs. recreational cannabis, abuse potential, etc.”

https://www.ncbi.nlm.nih.gov/pubmed/28983880

https://link.springer.com/article/10.1007%2Fs11926-017-0693-1

Bioactivities of alternative protein sources and their potential health benefits.

Posted on October 5, 2017 by David Worrell

“Increasing the utilisation of plant proteins is needed to support the production of protein-rich foods that could replace animal proteins in the human diet so as to reduce the strain that intensive animal husbandry poses to the environment. Lupins, quinoa and hempseed are significant sources of energy, high quality proteins, fibre, vitamins and minerals. In addition, they contain compounds such as polyphenols and bioactive peptides that can increase the nutritional value of these plants. From the nutritional standpoint, the right combination of plant proteins can supply sufficient amounts of essential amino acids for human requirements. This review aims at providing an overview of the current knowledge of the nutritional properties, beneficial and non-nutritive compounds, storage proteins, and potential health benefits of lupins, quinoa and hempseed.”

https://www.ncbi.nlm.nih.gov/pubmed/28804797

http://pubs.rsc.org/en/Content/ArticleLanding/2017/FO/C7FO00302A#!divAbstract

Efficacy and Tolerability of Phytomedicines in Multiple Sclerosis Patients: A Review.

Posted on September 28, 2017 by David Worrell

“Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) that can cause cognition, mobility, and sensory impairments. It is considered one of the most common non-traumatic causes of disability in the world. The aim of the present article was to review the clinical evidence related to medicinal plants in the management of MS symptoms. Electronic databases, including the Cochrane Library, Pubmed, and Scopus, were searched for entries from 1966 to February 2017. Only clinical studies were included in this review. Different medicinal plants have positive effects on MS, including Andrographis paniculata, Boswellia papyrifera, Ruta graveolens, Vaccinium spp., Camellia sinensis, Panax ginseng, Aloysia citrodora, Ginkgo biloba, Oenothera biennis, and Cannabis sativa. C. sativa had the highest level of clinical evidence, supporting its efficacy in MS symptoms. Proanthocyanidins, ginkgo flavone glycosides, ginsenosides, epigallocatechin-3-gallate, cannabinoids (including delta-9-tetrahydrocannabinol and cannabidiol), boswellic acid, and andrographolide were presented as the main bioactive components of medicinal plants with therapeutic benefits in MS. The main complications of MS in which natural drugs were effective include spasticity, fatigue, scotoma, incontinence, urinary urgency, nocturia, memory performance, functional performance, and tremor. Herbal medicines were mostly well tolerated, and the adverse effects were limited to mild to moderate. Further well-designed human studies with a large sample size and longer follow-up period are recommended to confirm the role of medicinal plants and their metabolites in the management of MS.” https://www.ncbi.nlm.nih.gov/pubmed/28948486

https://link.springer.com/article/10.1007%2Fs40263-017-0466-4

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Targeting the Endocannabinoid System to Treat Sepsis

Posted on September 26, 2017 by David Worrell

“Sepsis is a complex immune disorder that can affect the function of almost all organ systems in the body. This disorder is characterised by a malfunctioning immune response to an infection that involves both pro-inflammatory and immunosuppressive mediators. This leads to severe damage and failure of vital organs, resulting in patient death. Sepsis, septic shock, and systemic inflammatory response syndrome are the leading causes of mortality in surgical intensive care unit patients internationally. The current lack of viable therapeutic treatment options for sepsis underscores our insufficient understanding of this complex disease. The endocannabinoid system, a key regulator of essential physiological functions including the immune system, has recently emerged as a potential therapeutic target for sepsis treatment. The endocannabinoid system acquires its name from the plant Cannabis Sativa, which has been used medically to treat a variety of ailments, as well as recreationally for centuries. Cannabis Sativa contains more than 60 active phytocannabinoids with the primary phytocannabinoid Δ9-tetrahydrocannabinol (THC), (6) activating both endogenous endocannabinoid receptors. The endocannabinoid system represents a potential therapeutic target in sepsis due to the presence of cannabinoid receptors (CB2) on immune cells. In this review we discuss how various targets within the endocannabinoid system can be manipulated to treat the immune consequences of sepsis. One of the targets outlined are the endocannabinoid receptors and modulation of their activity through pharmacological agonists and antagonists. Another therapeutic target covered in this review is the modulation of the endocannabinoid degradative enzyme’s activity. Modulation of degradative enzyme activity can change the levels of endogenous cannabinoids thereby altering immune activity. Overall, activation of the CB2 receptors causes immunosuppression and can be beneficial during the hyperactivated immune state of sepsis, while suppression of the CB2 receptors may be beneficial during a hypoimmune septic state. The endocannabinoid system modulates the immune response in experimental sepsis. Manipulating the endocannabinoid system may have potential therapeutic benefit in clinical sepsis where immune and inflammatory dysfunction can be detrimental. Multiple targets exist within the endocannabinoid system, e.g. the system can be targeted at the level of receptors by administration of synthetic compounds, similar to the endocannabinoids, which either increase or inhibit receptor activation to provide the desired therapeutic effect. Alternatively, the endogenous enzymes that degrade endocannabinoids or cannabinoid-like lipids can also be targeted in order to manipulate the levels of endocannabinoids. Proper identification of the septic stage is crucial to determine the adequate therapeutic response that will be most beneficial. Due to the biphasic nature of sepsis immunopathology, immune suppression through endocannabinoid modulation can help mitigate the hyper-immune response during the early septic state, while immune activation may be beneficial in later stages.” http://www.signavitae.com/2013/05/targeting-the-endocannabinoid-system-to-treat-sepsis/ http://www.signavitae.com/2013/05/targeting-the-endocannabinoid-system-to-treat-sepsis/]]>

Cannabidiol attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation and neutrophil-mediated injury.

Posted on September 24, 2017 by David Worrell

“Cannabidiol (CBD) is a non-psychoactive component of marijuana, which has anti-inflammatory effects. It has also been approved by FDA for various orphan diseases for exploratory trials. Herein, we investigated the effects of CBD on liver injury induced by chronic plus binge alcohol feeding in mice. CBD may have therapeutic potential in the treatment of alcoholic liver diseases associated with inflammation, oxidative stress and steatosis, which deserves exploration in human trials.” https://www.ncbi.nlm.nih.gov/pubmed/28935932 “Cannabidiol (CBD) is the most abundant non-psychoactive constituent of marijuana plant (Cannabis Sativa) with excellent safety profile in humans even after chronic use. In conclusion, we demonstrate that CBD treatment significantly attenuates liver injury induced by chronic plus binge alcohol in a mouse model and oxidative burst in human neutrophils. CBD ameliorates alcohol-induced liver injury by attenuating inflammatory response involving E-selectin expression and neutrophil recruitment, and consequent oxidative/nitrative stress, in addition to attenuation of the alcohol-induced hepatic metabolic dysregulation and steatosis. These beneficial effects, coupled with the proven safety of CBD in human clinical trials and its current orphan drug approval by FDA for various indications suggest that it may have therapeutic potential in liver disease associated with inflammation, oxidative stress, metabolic dysregulation and steatosis.” https://www.nature.com/articles/s41598-017-10924-8]]>

Challenges towards Revitalizing Hemp: A Multifaceted Crop.

Posted on September 12, 2017 by David Worrell

“Hemp has been an important crop throughout human history for food, fiber, and medicine. Despite significant progress made by the international research community, the basic biology of hemp plants remains insufficiently understood. Clear objectives are needed to guide future research. As a semi-domesticated plant, hemp has many desirable traits that require improvement, including eliminating seed shattering, enhancing the quantity and quality of stem fiber, and increasing the accumulation of phytocannabinoids. Methods to manipulate the sex of hemp plants will also be important for optimizing yields of seed, fiber, and cannabinoids. Currently, research into trait improvement is hindered by the lack of molecular techniques adapted to hemp. Here we review how addressing these limitations will help advance our knowledge of plant biology and enable us to fully domesticate and maximize the agronomic potential of this promising crop.” https://www.ncbi.nlm.nih.gov/pubmed/28886910 http://www.cell.com/trends/plant-science/fulltext/S1360-1385(17)30177-2?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1360138517301772%3Fshowall%3Dtrue]]>

Clinical and Pre-Clinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol.

Posted on September 7, 2017 by David Worrell

“The plant Cannabis sativa, commonly called cannabis or marijuana, has been used for its psychotropic and mind-altering side effects for millennia. There has been growing attention in recent years on its potential therapeutic efficacy as municipalities and legislative bodies in the United States, Canada, and other countries grapple with enacting policy to facilitate the use of cannabis or its constituents for medical purposes. There are over 550 chemical compounds and over 100 phytocannabinoids isolated from cannabis, including Δ⁹-tetrahydrocannabinol (THC) and Cannabidiol (CBD). THC is thought to produce the main psychoactive effects of cannabis, while CBD does not appear to have similar effects. Studies conflict as to whether CBD attenuates or exacerbates the behavioral and cognitive effects of THC. This includes effects of CBD on THC induced anxiety, psychosis and cognitive deficits. In this article, we review the available evidence on the pharmacology and behavioral interactions of THC and CBD from pre-clinical and human studies particularly with reference to anxiety and psychosis like symptoms. Both THC and CBD, as well as other cannabinoid molecules, are currently being evaluated for medicinal purposes, separately and in combination. Future cannabis-related policy decisions should include consideration of scientific findings including the individual and interactive effects of CBD and THC.” https://www.ncbi.nlm.nih.gov/pubmed/28875990 https://www.nature.com/npp/journal/vaop/naam/abs/npp2017209a.html]]>

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