Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview.

“The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the more common.

Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required.

In particular, the attention of researchers has been focused on phytochemical compounds that have shown antioxidative, anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties and that could represent important resources in the discovery of drug candidates against dementia.

In this review, we summarize the neuroprotective effects of the main phytochemicals belonging to the polyphenol, isothiocyanate, alkaloid and cannabinoid families in the prevention and treatment of the most common kinds of dementia.

We believe that natural phytochemicals may represent a promising sources of alternative medicine, at least in association with therapies approved to date for dementia.”

http://www.ncbi.nlm.nih.gov/pubmed/27110749

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

Image result for Curr Clin Pharmacol.

“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

Safety and Efficacy of Medical Cannabis Oil for Behavioral and Psychological Symptoms of Dementia: An-Open Label, Add-On, Pilot Study.

“Tetrahydrocannabinol (THC) is a potential treatment for Alzheimer’s disease (AD).

OBJECTIVE:

To measure efficacy and safety of medical cannabis oil (MCO) containing THC as an add-on to pharmacotherapy, in relieving behavioral and psychological symptoms of dementia (BPSD).

Eleven AD patients were recruited to an open label, 4 weeks, prospective trial.

RESULTS:

Ten patients completed the trial. Significant reduction in CGI severity score and NPI score were recorded. NPI domains of significant decrease were: Delusions, agitation/aggression, irritability, apathy, and sleep and caregiver distress.

CONCLUSION:

Adding MCO to AD patients’ pharmacotherapy is safe and a promising treatment option.”

http://www.ncbi.nlm.nih.gov/pubmed/26757043

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

Cannabinoids for the Treatment of Agitation and Aggression in Alzheimer’s Disease.

“Alzheimer’s disease (AD) is frequently associated with neuropsychiatric symptoms (NPS) such as agitation and aggression, especially in the moderate to severe stages of the illness. The limited efficacy and high-risk profiles of current pharmacotherapies for the management of agitation and aggression in AD have driven the search for safer pharmacological alternatives.

Over the past few years, there has been a growing interest in the therapeutic potential of medications that target the endocannabinoid system (ECS).

The behavioural effects of ECS medications, as well as their ability to modulate neuroinflammation and oxidative stress, make targeting this system potentially relevant in AD.

This article summarizes the literature to date supporting this rationale and evaluates clinical studies investigating cannabinoids for agitation and aggression in AD.

Letters, case studies, and controlled trials from four electronic databases were included. While findings from six studies showed significant benefits from synthetic cannabinoids-dronabinol or nabilone-on agitation and aggression, definitive conclusions were limited by small sample sizes, short trial duration, and lack of placebo control in some of these studies.

Given the relevance and findings to date, methodologically rigorous prospective clinical trials are recommended to determine the safety and efficacy of cannabinoids for the treatment of agitation and aggression in dementia and AD.”

Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia

“In this randomized, double-blind, placebo-controlled, crossover trial, we evaluated the safety, pharmacodynamics, and pharmacokinetics of THC…

Older people with dementia and physical comorbidity could greatly benefit from the therapeutic application of cannabinoids. Recent studies have demonstrated that low doses of THC are effective in protecting the brain from neuroinflammation-induced cognitive damage.

Our findings suggest that low THC doses are safe and well tolerated by frail older persons with dementia.”

http://link.springer.com/article/10.1007/s00213-015-3889-y

“Our findings suggest that low THC doses are safe and well tolerated by frail older persons with dementia.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480847/

 

Cannabis News: The Cannabinoid System Reverses Dementia, Treats PTSD and Controls Diabetes Top May’s News Digest from Publius

“The Cannabinoid System’s role in reversing dementia, treating PTSD and controlling diabetes highlight May’s cannabis news from Publius, the pen name used by the authors of The Cannabis Papers – Federal ignorance goes on unabated.”

“The Cannabinoid System’s (CS) role in reversing dementia, treating PTSD and controlling diabetes highlight May’s cannabis news from Publius, the pen name used by the authors of The Cannabis Papers: A citizen’s guide to cannabinoids (2011).”

More: http://www.prweb.com/releases/2013/5/prweb10787154.htm

The endocannabinoid system and its therapeutic exploitation.

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“The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the endocannabinoid system might be realized in the years to come.”  http://www.ncbi.nlm.nih.gov/pubmed/15340387

http://www.nature.com/nrd/journal/v3/n9/full/nrd1495.html

New Study Shows Cannabis May Reverse Symptoms of Dementia

“In what could turn out to be a groundbreaking study, a group from Neuroscience Research Australia has been examining if cannabidiol – one of the main ingredients in cannabis – could reverse some of the symptoms of dementia, specifically Alzheimer’s disease. Early research for the study has found that it does.” images

“In the study, mice were injected with a disease analogous to Alzheimer’s, and then given doses of cannabidiol. The results so far are quite drastic; “It basically brings the performance of the animals back to the level of healthy animals,” said Tim Karl, one of the study’s researchers.

He goes on, “You could say it cured them, but we will have to go back and look at their brains to be sure.”

As part of the research,  the group also found that treating certain harmful cells associated with Alzheimer’s with cannabidiol reduced the amount of the harmful protein that they produced.”

http://thejointblog.com/new-study-shows-cannabis-may-reverse-symptoms-of-dementia/

Cannabis may help reverse dementia: study

“It makes most people a little foggy-headed, but scientists are investigating whether an active ingredient in cannabis could actually stave off dementia.

A team from Neuroscience Research Australia is in the early stages of research examining if one of the main active ingredients in cannabis, called cannabidiol, could reverse some of the symptoms of memory loss in animals.

Tim Karl, a senior research fellow with the group, said cannabidiol does not have the same psychoactive effects as the main component of marijuana, THC, but it has been found to have anti-inflammatory, antioxidant and other effects that could be beneficial for the brain.”

Read more: http://www.narrominenewsonline.com.au/story/1283217/cannabis-may-help-reverse-dementia-study/

The endocannabinoid system in targeting inflammatory neurodegenerative diseases.

“The classical divide between degenerative and inflammatory disorders of the CNS is vanishing as accumulating evidence shows that inflammatory processes are important in the pathophysiology of primarily degenerative disorders, and neurodegeneration complicates primarily inflammatory diseases of the brain and spinal cord. Here, we review the contribution of degenerative and inflammatory processes to CNS disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis and HIV-associated dementia.

An early combination of neuroprotective and anti-inflammatory approaches to these disorders seems particularly desirable because isolated treatment of one pathological process might worsen another.

We also discuss the apparently unique opportunity to modify neurodegeneration and neuroinflammation simultaneously by pharmacological manipulation of the endocannabinoid system in the CNS and in peripheral immune cells. Current knowledge of this system and its involvement in the above CNS disorders are also reviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/17350694