Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic.

“The limited effectiveness of current therapies against Alzheimer’s disease (AD) highlights the need for intensifying research efforts devoted to developing new agents for preventing or retarding the disease process. During the last few years, targeting the endogenous cannabinoid system has emerged as a potential therapeutic approach to treat Alzheimer.

The endocannabinoid system is composed by a number of cannabinoid receptors, including the well-characterized CB1 and CB2 receptors… Several findings indicate that the activation of both CB1 and CB2 receptors by natural or synthetic agonists, at non-psychoactive doses, have beneficial effects in Alzheimer experimental models…

Moreover, endocannabinoid signaling has been demonstrated to modulate numerous concomitant pathological processes, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress.

The present paper summarizes the main experimental studies demonstrating the polyvalent properties of cannabinoid compounds for the treatment of AD, which together encourage progress toward a clinical trial.”

http://www.ncbi.nlm.nih.gov/pubmed/24634659

“Considering the numerous complex pathological mechanisms involved in the progression of AD, treatments targeting a single causal or modifying factor offer limited benefit. Cannabinoids, however, exhibit pleiotropic activity, targeting in parallel several processes that play key roles in AD…”

Full: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942876/

“Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation…Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.” http://www.jneurosci.org/content/25/8/1904.long

Therapeutic Potential of Cannabinoids in Schizophrenia.

“Increasing evidence suggests a close relationship between the endocannabinoid system and schizophrenia.

The endocannabinoid system comprises of two G protein-coupled receptors (the cannabinoid receptors 1 and 2 [CB1 and CB2] for marijuana’s psychoactive principle Δ9-tetrahydrocannabinol), their endogenous small lipid ligands (namely anandamide [AEA] and 2-arachidonoylglycerol [2-AG], also known as endocannabinoids), and proteins for endocannabinoid biosynthesis and degradation.

…antipsychotic compounds which manipulate this system may provide a novel therapeutic target for the treatment of schizophrenia.

The present article reviews current available knowledge on herbal, synthetic and endogenous cannabinoids with respect to the modulation of schizophrenic symptomatology.

Furthermore, this review will be highlighting the therapeutic potential of cannabinoid-related compounds and presenting some promising patents targeting potential treatment options for schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/24605939

Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain

“Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia.

Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915876/

Cannabis (Medical Marijuana) Treatment for Motor and Non-Motor Symptoms of Parkinson Disease: An Open-Label Observational Study.

“The use of cannabis as a therapeutic agent for various medical conditions has been well documented…The aim of the present open-label observational study was to assess the clinical effect of cannabis on motor and non-motor symptoms of Parkinson disease (PD).

Analysis of specific motor symptoms revealed significant improvement after treatment…

There was also significant improvement of sleep and pain scores. No significant adverse effects of the drug were observed.

The study suggests that cannabis might have a place in the therapeutic armamentarium of PD.”

http://www.ncbi.nlm.nih.gov/pubmed/24614667

A comparison of cannabidiolic acid with other treatments for anticipatory nausea using a rat model of contextually elicited conditioned gaping

“The effectiveness of cannabidiolic acid (CBDA) was compared with other potential treatments for anticipatory nausea (AN), using a rat model of contextually elicited conditioned gaping reactions…

Conclusions

CBDA has therapeutic potential as a highly potent and selective treatment for AN without psychoactive or locomotor effects.”

http://link.springer.com/article/10.1007/s00213-014-3498-1

Role of the Endocannabinoid System in the Neuroendocrine Responses to Inflammation.

“… the endocannabinoid system has been recognized as a major neuromodulatory system whose main functions are to exert and maintain the body homeostasis.

The coordinated neural, immune, behavioral and endocrine responses to inflammation are orchestrated to provide an important defense against infections and help homeostasis restoration in the body. These responses are executed and controlled mainly by the hypothalamic-pituitary adrenal axis. Also, the hypothalamic-neurohypophyseal system is essential for survival and plays a role recovering the homeostasis under a variety of stress conditions, including inflammation and infection.

Since the endocannabinoid system components are present at sites involved in the hypothalamic-pituitary axis regulation, several studies were performed in order to investigate the endocannabinoid-mediated neurotransmitters and hormones secretion under physiological and pathological conditions.

In the present review we focused on the endocannabinoids actions on the neuroendocrine response to inflammation and infection. We provide a detailed overview of the current understanding of the role of the endocannabinoid system in the recovering of homeostasis as well as potential pharmacological therapies based on the manipulation of endocannabinoid system components that could provide novel treatments for a wide range of disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24588819

Target-Selective Phototherapy Using a Ligand-Based Photosensitizer for Type 2 Cannabinoid Receptor.

“Phototherapy is a powerful, noninvasive approach for cancer treatment, with several agents currently in clinical use.

…we developed a phototherapy agent that combines a functional ligand and a near infrared phthalocyanine dye. Our target is type 2 cannabinoid receptor (CB2R), considered an attractive therapeutic target for phototherapy given it is overexpressed by many types of cancers that are located at a surface or can be reached by an endoscope.

Overall, this opens up the opportunity for development of an alternative treatment option for CB2R-positive cancers.”

http://www.ncbi.nlm.nih.gov/pubmed/24583052

Marijuana as a possible treatment for HIV and cancer

Marijuana

“There’s been some interesting research on using THC (tetrahydrocannabinol), the principal psychoactive drug in marijuana, to help fight HIV, and damage cancer cells in some leukemias and possibly malignant tumors.

…the possibility exists that information from both of these research studies may produce beneficial results in the treatment of HIV and cancer.”

More: http://americablog.com/2014/02/marijuana-treatment-hiv-cancer.html

Weed Could Block H.I.V.’s Spread. No, Seriously.

“But the U.S. government won’t let scientists try out this promising treatment on humans… proving that an illegal drug can stop a deadly disease in humans—without testing it on them—is impossible…

THC is one of 500 active ingredients in marijuana. And marijuana, despite many studies proving its medical value, is sill classified by the government as a Schedule 1 Substance.

In the face of mounting evidence that it is beneficial in treating diseases… it remains a controlled substance.

During HIV infection, one of the earliest effects is that the virus spreads rapidly throughout the body and kills a significant part of cells in the gut and intestine. This activity damages the gut in a way that allows the HIV to leak through the cell wall of the intestines and into the bloodstream.

When THC is introduced into this environment, it activates the CB2 receptors in the intestines to build new, healthy bacterial cells that block the virus from leaking through the cell walls. In other words, the body works hard to keep bad stuff in the intestines and the good stuff out.

Put another way: HIV kills the cells that protect the walls— THC brings them back. Reducing the amount of the virus in the lower intestines could then help keep uninfected people uninfected.”

More: http://www.thedailybeast.com/articles/2014/02/15/weed-can-block-h-i-v-s-spread-no-seriously.html

Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice.

“Patients suffering from Alzheimer’s disease (AD) exhibit a decline in cognitive abilities including an inability to recognise familiar faces…

The non-psychoactive phytocannabinoid cannabidiol (CBD) exerts neuroprotective, anti-oxidant and anti-inflammatory effects and promotes neurogenesis. CBD also reverses Aβ-induced spatial memory deficits in rodents.

This is the first study to investigate the effect of chronic CBD treatment on cognition in an AD transgenic mouse model.

Our findings suggest that CBD may have therapeutic potential for specific cognitive impairments associated with AD.”

http://www.ncbi.nlm.nih.gov/pubmed/24577515