“The present study shows that chronic administration of the cannabinoid receptor type 1 (CB1) receptor agonist arachidonyl-2-chloroethylamide (ACEA) at pre-symptomatic or at early symptomatic stages, at a non-amnesic dose, reduces the cognitive impairment observed in double AβPP(swe)/PS1(1dE9) transgenic mice from 6 months of age onwards…
… targeting the CB1 receptor could offer a versatile approach for the treatment of Alzheimer’s disease.”
“Cannabinoids have been widely reported to have neuroprotective properties in vitro and in vivo. In this study we compared the effects of CB1 and CB2 receptor-selective ligands, the endocannabinoid anandamide and the phytocannabinoid cannabidiol, against oxidative stress and the toxic hallmark Alzheimer’s protein, β-amyloid (Aβ)…
…the endocannabinoid anandamide protects neuronal cells from Aβ exposure via a pathway unrelated to CB1 or CB2 receptor activation…protective effect of cannabidiol against oxidative stress…
…divergent pathways for neuroprotection of these two cannabinoids.”
http://www.ncbi.nlm.nih.gov/pubmed/22172925
https://www.sciencedirect.com/science/article/abs/pii/S0304394011015667
“Cannabinoids have neuroprotective effects that are exerted primarily through cannabinoid CB1 receptors in the brain. This study characterized CB1 receptor distribution in the double transgenic (dtg) APP(swe)/PS1(ΔE9) mouse model for Alzheimer’s disease. Immunohistochemical labeling of CB1 protein in non-transgenic mice revealed that CB1 was highly expressed in the hippocampus, with the greatest density of CB1 protein observed in the combined hippocampal subregions CA2 and CA3 (CA2/3). CB1 immunoreactivity in the CA1 and CA2/3 hippocampal regions was significantly decreased in the dtg APP(swe)/PS1(ΔE9) mice compared to non-transgenic littermates. Reduced CB1 expression in dtg APP(swe)/PS1(ΔE9) mice was associated with astroglial proliferation and elevated expression of the cytokines inducible nitric oxide synthase and tumor necrosis factor alpha. This finding suggests an anti-inflammatory effect of cannabinoids that is mediated by CB1 receptor, particularly in the CA2/3 region of the hippocampus. Furthermore, the study suggests a decreased CB1 receptor expression may result in diminished anti-inflammatory processes, exacerbating the neuropathology associated with Alzheimer’s disease.”
“The cannabinoid CB1-receptor is among the most abundant G-protein-coupled receptors in the mammalian brain. Whereas post-mortem studies in Alzheimer´s disease (AD) brains compared to age-matched controls have reported decreased CB1-receptor binding but no change in their protein levels (immunoreactivity), decreased or increased CB1-receptor protein levels have been reported in APP/PS1 transgenic mice modelling AD. To complete the picture, the present study used functional autoradiography to assess CB1-receptor-dependent Gi protein activation in the hippocampus, entorhinal cortex and medial frontal cortex of 13- to14-month-old female APPswe/PS1dE9 transgenic and wild-type littermate control mice. The mouse brains were processed for [35S]GTPγS autoradiography so that brain sections were analysed in pairs of one transgenic and one control mouse brain. The autoradiography protocol was completed for each pair both in the absence and presence of dithiotreitol (DTT) to reveal possible redox-dependent alterations in CB1 receptor function. Five treatments were used: baseline, incubation with 10 μM GTPγS to assess non-specific binding, and CB1 receptor agonist CP55,940 in three concentrations. By and large we found no statistically significant differences between the APP/PS1 transgenic and control mice in CB1 receptor signalling. The only exception was a modest redox-dependent alteration in entorhinal cortical CB1 receptors between the genotypes. Thus, in accordance with the majority of earlier human AD findings, we did not find evidence for notable changes in the number of functional CB1 receptors in the common APPswe/PS1dE9 mouse model of AD.”
…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.”
Free full text: http://www.jneurosci.org/content/25/8/1904.long
“The endocannabinoids and their attending cannabinoid (CB)(1) receptors have been implicated in the control of cognition, but their possible roles in dementias are still unclear.
The results suggest that an Aβ(42)-dependent impairment in brain anandamide mobilization contributes to cognitive dysfunction in AD.”
“Aberrant Notch signaling has recently emerged as a possible mechanism for the altered neurogenesis, cognitive impairment, and learning and memory deficits associated with Alzheimer disease (AD). Recently, targeting the endocannabinoid system in models of AD has emerged as a potential approach to slow the progression of the disease process. Although studies have identified neuroprotective roles for endocannabinoids, there is a paucity of information on modulation of the pro-survival Notch pathway by endocannabinoids. In this study the influence of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol, on the Notch-1 pathway and on its endogenous regulators were investigated in an in vitro model of AD. We report that AEA up-regulates Notch-1 signaling in cultured neurons… In summary, AEA has the proclivity to enhance Notch-1 signaling in an in vitro model of AD, which may have relevance for restoring neurogenesis and cognition in AD.”
“Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a fatal neurodegenerative disorder that is characterized by the selective loss of motor neurons in the spinal cord, brain stem, and motor cortex. An estimated 30,000 Americans are living with ALS, which often arises spontaneously and afflicts otherwise healthy adults. More than half of ALS patients die within 2.5 years following the onset of symptoms.
A review of the scientific literature reveals an absence of clinical trials investigating the use of cannabinoids for ALS treatment. However, recent preclinical findings indicate that cannabinoids can delay ALS progression, lending support to anecdotal reports by patients that cannabinoids may be efficacious in moderating the disease’s development and in alleviating certain ALS-related symptoms such as pain, appetite loss, depression and drooling.
Writing in the March 2004 issue of the journal Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders, investigators at the California Pacific Medical Center in San Francisco reported that the administration of THC both before and after the onset of ALS symptoms staved disease progression and prolonged survival in animals compared to untreated controls.
Additional trials in animal models of ALS have shown that the administration of other naturally occurring and synthetic cannabinoids can also moderate ALS progression but not necessarily impact survival. One recent study demonstrated that blocking the CB1 cannabinoid receptor did extend life span in an ALS mouse model, suggesting that cannabinoids’ beneficial effects on ALS may be mediated by non-CB1 receptor mechanisms.
As a result, experts are calling for clinical trials to assess cannabinoids for the treatment of ALS. Writing in the American Journal of Hospice & Palliative Medicine in 2010, a team of investigators reported, “Based on the currently available scientific data, it is reasonable to think that cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease.” They concluded, “There is an overwhelming amount of preclinical and clinical evidence to warrant initiating a multicenter randomized, double-blind, placebo-controlled trial of cannabis as a disease-modifying compound in ALS.”