The therapeutic potential of the endocannabinoid system for Alzheimer’s disease.
Reply
Tag Archives: AD
Hope for cannabis-based drug for Alzheimer’s
“A compound derived from marijuana might one day help fight the memory loss associated with Alzheimer’s disease, a new study suggests.
“Researchers have shown that a synthetic drug similar to cannabis can help older rats perform better on a spatial memory task.
Over a period of three weeks, Gary Wenk at Ohio State University in Columbus, US, and colleagues injected the brains of young and old rats with an inflammatory molecule that created an immune response in the animals’ brains which mimics that seen in Alzheimer’s patients.
During the same period the researchers also injected some of the rats with a synthetic drug similar to cannabis, called WIN-55212-2, which stimulates the brain receptors that normally respond to cannabis compounds.
The rats that received WIN-55212-2 in both age groups found the platform faster than their control counterparts. However, the difference between the treated and untreated animals’ performance was greatest among the older rats. The brains of rats receiving the synthetic drug also showed less sign of inflammation.
The results are impressive particularly because of the low dose of drug used in the experiment, comments Ken Mackie at the University of Washington in Seattle, US, who was not involved in the study.
“They gave them a relatively low dose, even for a rat.” Mackie says that this aspect of the study makes the prospect of developing a similar treatment for humans with Alzheimer’s disease “more promising”.
Wenk cautions, however, that WIN-55212-2 still causes psychoactive effects similar to cannabis, and as such is not yet a candidate for human use. Researchers are currently trying to develop a similar drug that could control inflammation in the brain without a concomitant high.”
Read more: http://www.newscientist.com/article/dn10330-hope-for-cannabisbased-drug-for-alzheimers.html
Scientists are high on idea that marijuana reduces memory impairment
“The more research they do, the more evidence Ohio State University scientists find that specific elements of marijuana can be good for the aging brain by reducing inflammation there and possibly even stimulating the formation of new brain cells.
The research suggests that the development of a legal drug that contains certain properties similar to those in marijuana might help prevent or delay the onset of Alzheimer’s disease. Though the exact cause of Alzheimer’s remains unknown, chronic inflammation in the brain is believed to contribute to memory impairment.
Any new drug’s properties would resemble those of tetrahydrocannabinol, or THC, the main psychoactive substance in the cannabis plant, but would not share its high-producing effects.
.”Could people smoke marijuana to prevent Alzheimer’s disease if the disease is in their family? We’re not saying that, but it might actually work. What we are saying is it appears that a safe, legal substance that mimics those important properties of marijuana can work on receptors in the brain to prevent memory impairments in aging. So that’s really hopeful,” Wenk said”
Read more: http://phys.org/news146320102.html
Anti-inflammatory property of the cannabinoid agonist WIN-55212-2 in a rodent model of chronic brain inflammation
“Cannabinoid receptors (CBr) stimulation induces numerous central and peripheral effects. A growing interest in the beneficial properties of manipulating the endocannabinoid system has lead to the possible involvement of CBr in the control of brain inflammation… Our results emphasize the potential use of CBr agonists in the regulation of inflammatory processes within the brain; this knowledge may lead to the use of CBr agonists in the treatment of neurodegenerative diseases associated with chronic neuroinflammation, such as Alzheimer disease.”
“The current report is the first to our knowledge to demonstrate the modulatory role of cannabinoids in an animal model of chronic neuroinflammation, pointing out the effectiveness of a CBr agonist on the consequences of LPS mediated neuroinflammation at a dose (0.5 mg/kg/day i.p. of WIN-55212-2) that does not impair performance in a patial memory task. These results further advocate for the manipulation of the endocannabinoid system to diminish the consequences of neuroinflammation in progression of AD and others inflammation-related diseases.”
Cannabinoid receptors and endocannabinoids: role in neuroinflammatory and neurodegenerative disorders.
Abstract
“The G-protein coupled receptors for Δ⁹-tetrahydrocannabinol, the major psychoactive principle of marijuana, are known as cannabinoid receptors of type 1 (CB₁) and 2 (CB₂) and play important functions in degenerative and inflammatory disorders of the central nervous system. Whilst CB₁ receptors are mostly expressed in neurons, where they regulate neurotransmitter release and synaptic strength, CB₂ receptors are found mostly in glial cells and microglia, which become activated and over-express these receptors during disorders such as Alzheimer’s disease, multiple sclerosis, amyotropic lateral sclerosis, Parkinson’s disease, and Huntington’s chorea. The neuromodulatory actions at CB₁ receptors by endogenous agonists (‘endocannabinoids’), of which anandamide and 2-arachidonoylglycerol are the two most studied representatives, allows them to counteract the neurochemical unbalances arising during these disorders. In contrast, the immunomodulatory effects of these lipophilic mediators at CB₂ receptors regulate the activity and function of glia and microglia. Indeed, the level of expression of CB₁ and CB₂ receptors or of enzymes controlling endocannabinoid levels, and hence the concentrations of endocannabinoids, undergo time- and brain region-specific changes during neurodegenerative and neuroinflammatory disorders, with the initial attempt to counteract excitotoxicity and inflammation. Here we discuss this plasticity of the endocannabinoid system during the aforementioned central nervous system disorders, as well as its dysregulation, both of which have opened the way to the use of either direct and indirect activators or blockers of CB₁ and CB₂ receptors for the treatment of the symptoms or progression of these diseases.”
Positron Emission Tomography Shows Elevated Cannabinoid CB (1) Receptor Binding in Men with Alcohol Dependence.
Abstract
“BACKGROUND:
Several lines of evidence link cannabinoid (CB) type 1 (CB (1) ) receptor-mediated endogenous CB (eCB) signaling to the etiology of alcohol dependence (AD). However, to date, only peripheral measures of eCB function have been collected in living humans with AD and no human in vivo data on the potentially critical role of the brain CB (1) receptor in AD have been published. This is an important gap in the literature, because recent therapeutic developments suggest that these receptors could be targeted for the treatment for AD.”
“CONCLUSIONS:
These findings agree with preclinical evidence and provide the first, albeit still preliminary in vivo evidence suggesting a role for brain CB (1) receptors in AD. The current study design does not answer the important question of whether elevated CB (1) receptors are a preexisting vulnerability factor for AD or whether elevations develop as a consequence of AD.”
Cannabinoid receptor 1 gene is associated with alcohol dependence.
Abstract
“BACKGROUND:
Alcohol dependence (AD) vulnerability is determined by a complex array of genetic factors. Given the potential role of endocannabinoid system in AD, polymorphisms within cannabinoid receptor 1 gene (CNR1) have been potentially associated with susceptibility to this disease. We thus aimed to examine the relationship between 3 allelic variants of CNR1 (rs6454674, rs1049353, and rs806368) and AD.
METHODS:
Genotyping of the aforementioned polymorphisms was carried out by PCR in 298 male alcoholics (187 of them with AD) and 155 healthy controls. Single-marker, haplotype, and interaction analysis were performed to analyze the influence of CNR1 gene on AD susceptibility.
RESULTS:
We found an association between CNR1 gene and AD after haplotype analysis. Alcoholic patients with TGT haplotype (corresponding to rs6454674-rs1049353-rs806368 polymorphisms in this order) were less prone to have AD (p = 0.017). Besides, alcoholics with a G/T substitution of the first marker (GGT haplotype) or a C/T substitution of the third marker (TGC haplotype) were more likely to develop AD (p = 0.006 and 0.004, respectively) and an interaction was found between the G allele of rs6454674 single nucleotide polymorphism (SNP) and the C allele of rs806368 SNP (p = 0.009).
CONCLUSIONS:
Our findings support previously reported associations of CNR1 with dependence to alcohol and other substances and emphasizes the relevance of endocannabinoid system in AD.”