Acetylcholinesterase inhibitors in Alzheimer’s disease

Posted on February 22, 2017 by David

“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/

Brain cannabinoid systems as targets for the therapy of neurological disorders.

Posted on February 20, 2017 by David

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“Unprecedented developments in cannabinoid research within the past decade include discovery of a brain (CB1) and peripheral (CB2) receptor; endogenous ligands, anandamide, and 2-arachidonylglycerol; cannabinoid drug-induced partial and inverse agonism at CB1 receptors, antagonism of NMDA receptors and glutamate, and antioxidant activity; and preferential CB1 receptor localization in areas subserving spasticity, pain, abnormal involuntary movements, seizures, and amnesia. These endogenous structures and chemicals and mechanisms are potentially new pathophysiologic substrates, and targets for novel cannabinoid treatments, of several neurological disorders.” https://www.ncbi.nlm.nih.gov/pubmed/9974182

“Endocannabinoid System in Neurological Disorders.” https://www.ncbi.nlm.nih.gov/pubmed/27364363

“Cannabinoids in the Treatment of Neurological Disorders” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604187/

β-Caryophyllene/Hydroxypropyl-β-Cyclodextrin Inclusion Complex Improves Cognitive Deficits in Rats with Vascular Dementia through the Cannabinoid Receptor Type 2 -Mediated Pathway.

Posted on February 6, 2017 by David

“This work was conducted to prepare β-caryophyllene-hydroxypropyl-β-cyclodextrin inclusion complex (HPβCD/BCP) and investigate its effects and mechanisms on cognitive deficits in vascular dementia (VD) rats.

Overall, the findings demonstrated the protective effects of HPβCD/BCP against cognitive deficits induced by chronic cerebral ischemia and suggested the potential of HPβCD/BCP in the therapy of vascular dementia in the future.”

https://www.ncbi.nlm.nih.gov/pubmed/28154534

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Cyclodextrin” https://en.wikipedia.org/wiki/Cyclodextrin

Historical perspective on the medical use of cannabis for epilepsy: Ancient times to the 1980s.

Posted on January 17, 2017 by David

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“There has been a dramatic surge in the interest of utilizing cannabis for epilepsy treatment in the US. Yet, access to cannabis for research and therapy is mired in conflicting regulatory policies and shifting public opinion. Understanding the current state of affairs in the medical cannabis debate requires an examination of the history of medical cannabis use. From ancient Chinese pharmacopeias to the current Phase III trials of pharmaceutical grade cannabidiol, this review covers the time span of cannabis use for epilepsy therapy so as to better assess the issues surrounding the modern medical opinion of cannabis use. This article is part of a Special Issue titled Cannabinoids and Epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/28089286

http://www.thctotalhealthcare.com/category/epilepsy-2/

Therapeutic Use of Cannabis in Inflammatory Bowel Disease.

Posted on January 6, 2017 by David

“The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis.

The plant Cannabis sativa has been used in medicinal practice for thousands of years. Anecdotal reports have suggested a therapeutic role for cannabis in the treatment of IBD for hundreds of years. A case report from 1990 describes patients with IBD maintaining remission of disease via cannabis use. Cannabinoids appear to have a clear role in gut pathology and offer a potential target for drug intervention in the treatment of IBD. Cannabis seems to be of symptomatic benefit to patients often refractory to conventional medicines.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193087/

A user’s guide to cannabinoid therapies in oncology.

Posted on January 5, 2017 by David

“”Cannabinoid” is the collective term for a group of chemical compounds that either are derived from the Cannabis plant, are synthetic analogues, or occur endogenously.

Although cannabinoids interact mostly at the level of the currently recognized cannabinoid receptors, they might have cross reactivity, such as at opioid receptors.

Patients with malignant disease represent a cohort within health care that have some of the greatest unmet needs despite the availability of a plethora of guideline-driven disease-modulating treatments and pain and symptom management options.

Cannabinoid therapies are varied and versatile, and can be offered as pharmaceuticals (nabilone, dronabinol, and nabiximols), dried botanical material, and edible organic oils infused with cannabis extracts. Cannabinoid therapy regimens can be creative, involving combinations of all of the aforementioned modalities.

Patients with malignant disease, at all points of their disease trajectory, could be candidates for cannabinoid therapies whether as monotherapies or as adjuvants.

The most studied and established roles for cannabinoid therapies include pain, chemotherapy-induced nausea and vomiting, and anorexia.

Moreover, given their breadth of activity, cannabinoids could be used to concurrently optimize the management of multiple symptoms, thereby reducing overall polypharmacy.

The use of cannabinoid therapies could be effective in improving quality of life and possibly modifying malignancy by virtue of direct effects and in improving compliance or adherence with disease-modulating treatments such as chemotherapy and radiation therapy.” https://www.ncbi.nlm.nih.gov/pubmed/28050136

“The Cannabis plant has a long and colourful history that spans more than 5000 years of world history and human usage. In contemporary times, the term “cannabis” has commonly been supplanted by the more colloquial term “marijuana” (also spelled “marihuana”). An extremely versatile and easily cultivatable plant, Cannabis was used by ancient cultures for food, fibre, and medicinal purposes. The integration and broader utilization of cannabinoid therapies within the domain of oncology (including palliation) carries the potential not only for improved health care outcomes for patients but also for economic savings and greater safety for society. Patient reports of improvement in quality of life, especially for those undergoing intensive treatment regimens, could be key to patients continuing with lifesaving or life-prolonging therapies.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5176373/

Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists.

Posted on December 26, 2016 by David

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“The misuse of prescription opiates is on the rise with combination therapies (e.g. acetaminophen or NSAIDs) resulting in severe liver and kidney damage. In recent years, cannabinoid receptors have been identified as potential modulators of pain and rewarding behaviors associated with cocaine, nicotine and ethanol in preclinical models. Yet, few studies have identified whether mu opioid agonists and CB2 agonists act synergistically to inhibit chronic pain while reducing unwanted side effects including reward liability.

We determined if analgesic synergy exists between the mu-opioid agonist morphine and the selective CB2 agonist, JWH015, in rodent models of acute and chronic inflammatory, post-operative, and neuropathic pain using isobolographic analysis. We also investigated if the MOR-CB2 agonist combination decreased morphine-induced conditioned place preference (CPP) and slowing of gastrointestinal transit. Co-administration of morphine with JWH015 synergistically inhibited preclinical inflammatory, post-operative and neuropathic-pain in a dose- and time-dependent manner; no synergy was observed for nociceptive pain. Opioid-induced side effects of impaired gastrointestinal transit and CPP were significantly reduced in the presence of JWH015.

Here we show that MOR + CB2 agonism results in a significant synergistic inhibition of preclinical pain while significantly reducing opioid-induced unwanted side effects.

The opioid sparing effect of CB2 receptor agonism strongly supports the advancement of a MOR-CB2 agonist combinatorial pain therapy for clinical trials.”

https://www.ncbi.nlm.nih.gov/pubmed/28007501

Tolerability of dronabinol alone, ondansetron alone and the combination of dronabinol plus ondansetron in delayed chemotherapy-induced nausea and vomiting.

Posted on December 14, 2016 by David

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“Dronabinol (Marinol), the synthetic version of tetrahydrocannabinol, is used to treat nausea and vomiting following cancer chemotherapy (CINV).

It has a unique mechanism of action (cannabinoid receptor binding) compared to the more frequently used serotonin receptor antagonists. Tolerability of dronabinol versus ondansetron and the combination of dronabinol plus ondansetron was explored in subjects with delayed CINV.

Dronabinol was well tolerated and resulted in few terminations due to adverse events. The low rate of CNS-related adverse events following D treatment may make it a suitable alternative to serotonin antagonist therapy for delayed CINV.”

https://www.ncbi.nlm.nih.gov/pubmed/27946950

Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy

Posted on December 13, 2016 by David

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“Parkinson’s disease (PD), a neurodegenerative disorder, is the second most common neurological illness in United States. Neurologically, it is characterized by the selective degeneration of a unique population of cells, the nigrostriatal dopamine neurons.

The current treatment is symptomatic and mainly involves replacement of dopamine deficiency. This therapy improves only motor symptoms of Parkinson’s disease and is associated with a number of adverse effects including dyskinesia. Therefore, there is unmet need for more comprehensive approach in the management of PD.

Cannabis and related compounds have created significant research interest as a promising therapy in neurodegenerative and movement disorders. In this review we examine the potential benefits of medical marijuana and related compounds in the treatment of both motor and nonmotor symptoms as well as in slowing the progression of the disease. The potential for cannabis to enhance the quality of life of Parkinson’s patients is explored.

Marijuana has been shown to improve nonmotor symptoms of PD such as depression, pain, sleep, and anxiety. Moreover, components of cannabis have been demonstrated to have neuroprotective effect due to their anti-inflammatory, antioxidative, and antiexcitotoxic properties.

Due to combination of the above mentioned beneficial effects, cannabis may provide a viable alternative or addition to the current treatment of Parkinson’s disease.” https://www.hindawi.com/journals/pd/2016/1279042/

“Marijuana: Could it slow Parkinson’s disease progression? Parkinson’s disease is the second most common neurological illness in the United States, causing tremors, slowness of movement, postural instability, and impaired balance and coordination. But findings from a new review suggest symptoms of the condition could be improved with marijuana.” http://www.medicalnewstoday.com/articles/314648.php

“Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy.” https://www.ncbi.nlm.nih.gov/pubmed/28050308

Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders.

Posted on December 12, 2016 by David

“Anxiety and trauma-related disorders are psychiatric diseases with a lifetime prevalence of up to 25%. Phobias and post-traumatic stress disorder (PTSD) are characterized by abnormal and persistent memories of fear-related contexts and cues. The effects of psychological treatments such as exposure therapy are often only temporary and medications can be ineffective and have adverse side effects.

Growing evidence from human and animal studies indicates that cannabidiol, the main non-psychotomimetic phytocannabinoid present in Cannabis sativa, alleviates anxiety in paradigms assessing innate fear.

More recently, the effects of cannabidiol on learned fear have been investigated in preclinical studies with translational relevance for phobias and PTSD.

Here we review the findings from these studies, with an emphasis on cannabidiol regulation of contextual fear.

The evidence indicates that cannabidiol reduces learned fear in different ways: (1) cannabidiol decreases fear expression acutely, (2) cannabidiol disrupts memory reconsolidation, leading to sustained fear attenuation upon memory retrieval, and (3) cannabidiol enhances extinction, the psychological process by which exposure therapy inhibits learned fear.

We also present novel data on cannabidiol regulation of learned fear related to explicit cues, which indicates that auditory fear expression is also reduced acutely by cannabidiol.

We conclude by outlining future directions for research to elucidate the neural circuit, psychological, cellular, and molecular mechanisms underlying the regulation of fear memory processing by cannabidiol.

This line of investigation may lead to the development of cannabidiol as a novel therapeutic approach for treating anxiety and trauma-related disorders such as phobias and PTSD in the future.”

https://www.ncbi.nlm.nih.gov/pubmed/27932983