Cannabinoid Receptor (CB1) Plays Crucial Role in Alzheimers Disease - Dr. Dave Hepburn

Tuesday, 9 October 2018


Article recommend by Dr. Dave Hepburn:

Genetic deletion of CB1 cannabinoid receptors exacerbates the Alzheimer-like symptoms in a transgenic animal model.

Abstract
Activating CB1 cannabinoid receptor has been demonstrated to produce certain therapeutic effects in animal models of Alzheimer's disease (AD). In this study, we evaluated the specific contribution of CB1 receptor to the progression of AD-like pathology in double transgenic APP/PS1 mice. A new mouse strain was generated by crossing APP/PS1 transgenic mice with CB1 knockout mice. Genetic deletion of CB1 drastically reduced the survival of APP/PS1 mice. In spite that CB1 mutant mice bearing the APP/PS1 transgene developed normally, they suddenly died within the first two months of life likely due to spontaneous seizures. This increased mortality could be related to an imbalance in the excitatory/inhibitory transmission in the hippocampus as suggested by the reduced density of inhibitory parvalbumin positive neurons observed in APP/PS1 mice lacking CB1 receptor at 7 weeks of age. We also evaluated the AD-like phenotype of APP/PS1 mice heterozygous for the CB1 deletion at 3 and 6 months of age. The memory impairment associated to APP/PS1 transgene was accelerated in these mice. Neither the soluble levels of Aβ or the density of Aβ plaques were modified in APP/PS1 mice heterozygous for CB1 deletion at any age. However, the reduction in CB1 receptor expression decreased the levels of PSD-95 protein in APP/PS1 mice, suggesting a synaptic dysfunction in these animals that could account for the acceleration of the memory impairment observed. In summary, our results suggest a crucial role for CB1 receptor in the progression of AD-related pathological events.

“Although several studies have shown that type-2 cannabinoid receptor (CB2R) is involved in Alzheimer's disease (AD) pathology, now a crucial role of CB1R has become evident. One of the more exciting areas of cannabis and endocannaboid research.”
Dr. Dave Hepburn

To read the full article please visit: 

Dr. David Hepburn website: 

US Study Shows Which Cannabis (and how) is Best for Insomnia.

Friday, 5 October 2018


Article recommend by Dr. David Hepburn:

Effectiveness of Raw, Natural Medical Cannabis Flower for Treating Insomnia under Naturalistic Conditions.

Abstract 

We use a mobile software application (app) to measure for the first time, which fundamental characteristics of raw, natural medical Cannabis flower are associated with changes in perceived insomnia under naturalistic conditions. Methods: Four hundred and nine people with a specified condition of insomnia completed 1056 medical cannabis administration sessions using the Releaf AppTM educational software during which they recorded real-time ratings of self-perceived insomnia severity levels prior to and following consumption, experienced side effects, and product characteristics, including combustion method, cannabis subtypes, and/or major cannabinoid contents of cannabis consumed. Within-user effects of different flower characteristics were modeled using a fixed effects panel regression approach with standard errors clustered at the user level. Results: Releaf AppTM users showed an average symptom severity reduction of -4.5 points on a 0⁻10 point visual analogue scale (SD = 2.7, d = 2.10, p < 0.001). Use of pipes and vaporizers was associated with greater symptom relief and more positive and context-specific side effects as compared to the use of joints, while vaporization was also associated with lower negative effects. Cannabidiol (CBD) was associated with greater statistically significant symptom relief than tetrahydrocannabinol (THC), but the cannabinoid levels generally were not associated with differential side effects. Flower from C. sativa plants was associated with more negative side effects than flower from C. indica or hybrid plant subtypes. Conclusions: Consumption of medical Cannabis flower is associated with significant improvements in perceived insomnia with differential effectiveness and side effect profiles, depending on the product characteristics. 

“There are simply too many who are addicted to prescription sleeping pills even though there is a concern that those who take even a few may development cognitive impairment. The cannabis that appears to help best with insomnia is a CBD dominant, vaporized (not smoked) “indica.” Though “indica” doesn’t specifically say which terpenes are involved I always recommend high myrcene and linalool.”
Dr. David Hepburn

To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pubmed/29997343

Dr. David Hepburn website:
doctordavidhepburn.com

Cannabis Extract Inhibits Superbug MRSA - Dr. David Hepburn

Wednesday, 3 October 2018


Article recommend by Dr. David Hepburn:

Antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava leaf extracts against methicillin-resistant Staphylococcus aureus.

Abstract 
OBJECTIVE: 
This study examined the antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava against methicillin-resistant Staphylococcus aureus (MRSA) and used a standardized purification protocol to determine the presence and abundance of bioactive compounds in the leaf extracts. 
METHODS: 
In vitro antimicrobial activities of the ethanolic extracts of C. sativa, T. orientalis and P. guajava were tested against MRSA. The presence of bioactive molecules in these three leaves was evaluated using biochemical assays and high-performance thin-layer chromatography (HPTLC). 
RESULTS:
Resistance to methicillin, penicillin, oxacillin and cefoxitin was observed in each of the clinical and nonclinical MRSA isolates. However, they were still vulnerable to vancomycin. Used individually, the 50% extract of each plant leaf inhibited MRSA growth. A profound synergism was observed when C. sativa was used in combination with T. orientalis (1:1) and when P. guajava was used in combination with T. orientalis (1:1). This was shown by larger zones of inhibition. This synergism was probably due to the combined inhibitory effect of phenolics present in the leaf extracts (i.e., quercetin and gallic acid) and catechin, as detected by HPTLC. 
CONCLUSION:
The leaf extracts of C. sativa, T. orientalis and P. guajava had potential for the control of both hospital- and community-acquired MRSA. Moreover, the inhibitory effect was enhanced when extracts were used in combination.

“MRSA is a terrible problem that every hospital and clinician fears. What an option this would prove to be. I have heard from several sources that certain cannabinoids and terpenes may do just as this study purports.”
Dr. David Hepburn


To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pubmed/30120078

Dr. David Hepburn website:
doctordavidhepburn.com




Schizophrenia More Likely to Lead to Cannabis Use…. Not the Reverse - Dr Dave Hepburn

Tuesday, 2 October 2018


Article recommend by Dr. Dave Hepburn:

GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia.

Abstract 
Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.

“It is well known that cannabis use is higher in those with schizophrenia. However, cannabis has never been shown to cause schizophrenia; in fact, the opposite appears to be true as more research is lining up showing that those with schizophrenia are more likely to turn to cannabis, possibly to help deal with the social isolation and/or a genetic predisposition as this study infers. Once again, any who claim that cannabis causes schizophrenia, are simply incorrect.” 
Dr. Dave Hepburn


To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pubmed/30150663

Dr. David Hepburn website:
doctordavidhepburn.com
   


Cannabinoid Receptor Protects Against Hearing Loss Caused by Chemotherapy - Dr. David Hepburn

Monday, 1 October 2018


Article recommend by Dr. David Hepburn:

The Endocannabinoid/Cannabinoid Receptor 2 System Protects Against Cisplatin-Induced Hearing Loss

Abstract
Previous studies have demonstrated the presence of cannabinoid 2 receptor (CB2R) in the rat cochlea which was induced by cisplatin. In an organ of Corti-derived cell culture model, it was also shown that an agonist of the CB2R protected these cells against cisplatin-induced apoptosis. In the current study, we determined the distribution of CB2R in the mouse and rat cochleae and examined whether these receptors provide protection against cisplatin-induced hearing loss. In a knock-in mouse model expressing the CB2R tagged with green fluorescent protein, we show distribution of CB2R in the organ of Corti, stria vascularis, spiral ligament and spiral ganglion cells. A similar distribution of CB2R was observed in the rat cochlea using a polyclonal antibody against CB2R. Trans-tympanic administration of (2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone (JWH015), a selective agonist of the CB2R, protected against cisplatin-induced hearing loss which was reversed by blockade of this receptor with 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone (AM630), an antagonist of CB2R. JWH015 also reduced the loss of outer hair cells (OHCs) in the organ of Corti, loss of inner hair cell (IHC) ribbon synapses and loss of Na+/K+-ATPase immunoreactivity in the stria vascularis. Administration of AM630 alone produced significant hearing loss (measured by auditory brainstem responses) which was not associated with loss of OHCs, but led to reductions in the levels of IHC ribbon synapses and strial Na+/K+-ATPase immunoreactivity. Furthermore, knock-down of CB2R by trans-tympanic administration of siRNA sensitized the cochlea to cisplatin-induced hearing loss at the low and middle frequencies. Hearing loss induced by cisplatin and AM630 in the rat was associated with increased expression of genes for oxidative stress and inflammatory proteins in the rat cochlea. In vitro studies indicate that JWH015 did not alter cisplatin-induced killing of cancer cells suggesting this agent could be safely used during cisplatin chemotherapy. These data unmask a protective role of the cochlear endocannabinoid/CB2R system which appears tonically active under normal conditions to preserve normal hearing. However, an exogenous agonist is needed to boost the activity of endocannabinoid/CB2R system for protection against a more traumatic cochlear insult, as observed with cisplatin administration.

“One of the several possible nasty side effects of a common anticancer medication, is hearing loss. Activation of CB2R appears to prevent this, indicating an important role of the ECS (endocannabinoid system) in neuroprotection."
Dr. David Hepburn

To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110918/

Dr. David Hepburn website:
doctordavidhepburn.com