“The endocannabinoid system has gained much attention as a new potential pharmacotherapeutic target in various neurodegenerative diseases, including Alzheimer’s disease (AD).
…The altered CB1 levels appear, rather, to be age-and/or pathology-dependent, indicating an involvement of the endocannabinoid system in AD pathology and supporting the ECS as a potential novel therapeutic target for treatment of AD.”
“The endocannabinoid CB2 receptor system has been implicated in the neuropathology of Alzheimer’s disease (AD)…
The results confirm the constitutive role of the CB2 receptor system both in reducing amyloid plaque pathology in AD and also support the potential of cannabinoid therapies targeting CB2 to reduce Aβ…”
“Designing drugs with a specific multi-target profile is a promising approach against multifactorial illnesses as Alzheimer’s disease. In this work, new indazole ethers that possess dual activity as both cannabinoid agonists CB2 and inhibitors of BuChE have been designed by computational methods…
The results of pharmacological tests have revealed that three of these derivatives behave as CB2 cannabinoid agonists and simultaneously show BuChE inhibition. In particular, compounds 3 and 24 have emerged as promising candidates as novel cannabinoids that inhibit BuChE by a non-competitive or mixed mechanism, respectively. On the other hand, both molecules show antioxidant properties.”
“The endocannabinoid system (ECS) is an important modulatory and potentially neuroprotective homeostatic system in the brain.
We have investigated CB1R availability in vivo in patients with AD…
In conclusion, we found no in vivo evidence for a difference in CB1R availability in AD compared to age-matched controls.
Taken together with recently reported in vivo CB1R changes in Parkinson’s and Huntington’s disease, these data suggest that the CB1R is differentially involved in neurodegenerative disorders.”
http://www.ncbi.nlm.nih.gov/pubmed/24189376
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“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.
The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.
In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”
http://www.ncbi.nlm.nih.gov/pubmed/24006213
http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract
“Early onset of age-related changes in the brain of cannabinoid 1 receptor knockout (Cnr1-/-) mice suggests that cannabinoid 1 (CB1) receptor activity significantly influences the progression of brain aging. In the present study we show that lack of CB1 receptors leads to a significant increase in lipofuscin accumulation and a reduced expression and activity of cathepsin D, lysosomal protease implicated in the degradation of damaged macromolecules, in the hippocampus of 12-month-old mice. The impaired clearance of damaged macromolecules due to the low cathepsin D levels and not enhanced oxidative stress may be responsible for the lipofuscin accumulation because macromolecule oxidation levels were comparable between the genotypes within the same age group. The altered levels of autophagy markers p62 and LC3-II suggest that autophagy is upregulated in CB1 knockout mice. Increased autophagic flux in the absence of CB1 receptors is probably a compensatory mechanism to partially counteract decreased lysosomal degradation capacity. Together, these results suggest that CB1 receptor activity affects lysosomal activity, degradation of damaged macromolecules and thus it may influence the course and onset of brain aging.”
“We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats.
Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson’s and Alzheimer’s, and has been related to cognitive deficits in animals and human subjects.
…we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats.
We found that CBD rescued iron-induced effects…
Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.”
“Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies.
Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases…
We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats…
A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats.
The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders.
Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.”
“Emerging evidence suggests beta-amyloid (Aβ) deposition in the Alzheimer’s disease (AD) brain is the result of impaired clearance, due in part to diminished Aβ transport across the blood–brain barrier (BBB). Recently, modulation of the cannabinoid system was shown to reduce Aβ brain levels and improve cognitive behavior in AD animal models…
The purpose of the current studies was to investigate the role of the cannabinoid system in the clearance of Aβ across the BBB.
The current studies demonstrate, for the first time, a role for the cannabinoid system in the transit of Aβ across the BBB.
These findings provide insight into the mechanism by which cannabinoid treatment reduces Aβ burden in the AD brain and offer additional evidence on the utility of this pathway as a treatment for AD.”
http://www.sciencedirect.com/science/article/pii/S104474311300064X
“A new study conducted by researchers at the Roskamp Institute in Florida, and published in the journal Molecular and Cellular Neuroscience, has found that cannabis can slow the effects of Alzheimer’s Disease, and may in fact be able to halt it entirely.”
“According to Corbin Bachmeier, Ph.D – who’s the lead researcher of the study – Alzheimer’s Disease is “the result of impaired Aβ [Amyloid-β protein] clearance from the brain”. According to this study, cannabis can solve this problem, making it a potential treatment…
This research validates past studies (including some presented earlier this year, as well as a 2006 study), though is the first to actually explain why cannabis can be beneficial to the disease.”
More: http://thejointblog.com/new-study-cannabis-can-slow-cure-alzheimers-disease/#more-7683