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CBD and NAD+ a very potent combination for fighting inflammation

Current research shows  the powerful role that inflammation plays as an underlying cause in most pervasive chronic conditions, whether we are talking about coronary artery disease, hypertension, diabetes, depression, rheumatoid arthritis, Alzheimer’s disease,  and other common conditions.

Ultimately, the main issue with higher levels of inflammation that manifests as damage to tissue is the fact that when inflammation has been turned on, it increases the production of damaging free radicals, a situation we call oxidative stress. When oxidative stress is running rampant, damage occurs to our proteins, and fat, and even our DNA.

Reducing dietary sugar and carbohydrates, while at the same time increasing dietary consumption of good fats, goes a long way towards reducing inflammation.

Emerging research now demonstrates that both CBD and NAD+ have significant potential in terms of limiting inflammation.

Both CBD and NAD+ have been touted for a wide variety of health issues, with strong scientific evidence  for  effectiveness in treating some of the cruelest childhood epilepsy syndromes, such as Dravet syndrome and Lennox-Gastaut syndrome (LGS), which typically don’t respond to antiseizure medications.

CBD is commonly used to address anxiety, and for patients who suffer through the misery of insomnia, studies suggest that CBD may help with both falling asleep and staying asleep.

CBD  demonstrates neuroinflammatory effects in mice with significant decrease of Il-6 and TNF markers of inflammation.

Dr. Nady Braidy presented at conference, NAD+ was shown to decrease IL-2, IL-6, and CRP markers of inflammation in humans.

Both CBD and NAD+ have been shown to cross the blood brain barrier more effectively when administered Intranasally.

Research on NAD+

Intranasal administration with NAD+ profoundly decreases brain injury in a rat model of transient focal ischemia (ying, 2007)

Increasing evidence has supported the hypothesis that PARP-1 induces cell death by depleting intracellular NAD+. We observed that intranasal NAD+ delivery significantly increased NAD+ contents in the brains.

Intranasal delivery with 10 mg / kg NAD+ at 2 hours after ischemic onset profoundly decreased infarct formation when assessed either at 24 or 72 hours after ischemia.

These results provide the first in vivo evidence that NAD+ metabolism is a new target for treating brain ischemia, and that NAD+ administration may be a novel strategy for decreasing brain damage in cerebral ischemia and possibly other PARP-1-associated neurological diseases.

Our results provide the first in vivo evidence that NAD+ administration can profoundly decrease brain damage under certain pathological conditions. It is noteworthy that NAD+ can reduce infarct formation by up to 86 % even when administered at 2 hrs after ischemic onset.

Compared with other studies that apply drugs during post-ischemia phases in order for decreasing ischemic brain injury, the protective effect of NAD+ could be one of the most profound effects ever reported. In this study we also provided evidence that by the intranasal delivery approach NAD+ can be delivered into the brains.
Contribution of P2X7 receptors to adenosine uptake by cultured mouse astrocytes (Okuda, 2010)

Extracellularly applied NAD(+) prevents astrocyte death caused by excessive activation of poly(ADP-ribose) polymerase-1, In this study, we examined whether the intact form of NAD(+) is incorporated into astrocytes. A large portion of extracellularly added NAD(+) was degraded into metabolites such as AMP and adenosine in the extracellular space. The uptake of adenine ring-labeled [(14)C]NAD(+), but not nicotinamide moiety-labeled [(3)H]NAD(+), Taken together, these results indicate that exogenous NAD(+) is degraded by ectonucleotidases and that adenosine, as its metabolite, is taken up into astrocytes via the P2X7R-associated channel/pore.

NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency

Neuronal death induced by misfolded prion protein is due to NAD+ depletion and can be relieved in vitro and in vivo by NAD+ replenishment

Our study reveals NAD+ starvation as a novel mechanism of autophagy activation and neurodegeneration induced by a misfolded amyloidogenic protein. We propose the development of NAD+ replenishment strategies for neuroprotection in prion diseases and possibly other protein misfolding neurodegenerative diseases.

we discovered that TPrP induces neuronal death via a profound depletion of intracellular nicotinamide adenine dinucleotide (NAD+) levels causing metabolic failure. Neuronal death can be rescued in vitro and in vivo by NAD+ replenishment.

our data demonstrate for the first time that a failure of NAD+ metabolism is the cause of neuronal ailing

misfolded amyloidogenic protein can induce neuronal death by genuine NAD+ starvation and that ailing neurons can be completely rescued by NAD+ treatment

our study shows that neuronal death induced by NAD+ depletion is reversible and that NAD+ replenishment mitigates neurodegeneration

We propose the development of NAD+-replenishment strategies for the treatment of prion diseases.

Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study (Demarin, 2004)

In previous trials NADH has been shown to improve cognitive functioning in patients with Parkinson's disease, depression and AD.

After 6 months of treatment, subjects treated with NADH showed no evidence of progressive cognitive deterioration and had significantly higher total scores on the MDRS compared with subjects treated with placebo (p < 0.05). Analysis of MDRS subscales revealed significantly better performance by NADH subjects on measures of verbal fluency (p = 0.019), visual-constructional ability (p = 0.038) and a trend (p = 0.08) to better performance on a measure of abstract verbal reasoning.

Consistent with earlier studies, the present findings support NADH as a treatment for AD.

Research on CBD

In research published in Free Radical Biology and Medicine, scientists at the University of Mississippi medical center describe the potential benefits of using CBD, which has been demonstrated to be specifically effective in dealing with various types of pain. This activity is also thought to represent a manifestation of CBD working as an anti-inflammatory.

Further, many of the health-related issues associated with obesity are a consequence of increased inflammation. CBD is being explored extensively in relation to obesity in hopes of reducing some of these important health consequences.

According to the authors:
Inflammation and oxidative stress are intimately involved in the genesis of many human diseases. Unraveling that relationship therapeutically has proven challenging, in part because inflammation and oxidative stress “feed off” each other. However, CBD would seem to be a promising starting point for further drug development given its anti-oxidant (although relatively modest) and anti-inflammatory actions on immune cells…

 The research in terms of medical application of CBD is expanding dramatically, and with good reason. As a natural, plant derived anti-inflammatory, CBD joins other familiar players in this arena like turmeric which is derived from curcumin, as well as ginger and many others.
Below are some other recent research studies on CBD for pain management and inflammation, with several specifically using Intranasal (IN) delivery.  Quotes are taken directly from the studies.

Nasal administration of drugs as a new non-invasive strategy for efficient treatment of multiple sclerosis
We investigated the efficiency of nasal drug administration as a new non-invasive treatment strategy for MS.

This work shows that nasal administration improved drug efficiency and stimulates further research for a non-invasive strategy for MS.

Finally, the nasal delivery system was found to be safe to the nasal mucosa following multiple administrations

It has been reported that a potential route of transport for exogenous materials to brain is a direct delivery from nose via the olfactory pathway thus by-passing the BBB

Results presented inFig. 5 show that nasal administration of CBD alone reduced the expression of IL-6 and TNF-α in the cerebellum tissues

The protective mechanism of cannabidiol in cardiac injury: A systematic review of non-clinical studies
Our findings obviously demonstrate that CBD has multi-functional protective assets to improve cardiac injuries; preliminary through scavenging of free radicals, and reduction of oxidative stress, apoptosis, and inflammation.

Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial
Cannabinoids are known to have analgesic properties.

The mean reduction in pain intensity scores (primary outcome measure) was greater in patients receiving sativex than placebo (mea adjusted scores1.48 points vs.0.52 points on a 0–10 Numerical Rating Scale (p= 0.004; 95% CI:1.59,0.32). Improvements in Neuropathic Pain Scale composite score (p= 0.007), sleep NRS (p= 0.001), dynamic allodynia (p= 0.042), punctate allodynia(p= 0.021), Pain Disability Index (p= 0.003) and Patient’s Global Impression of Change (p< 0.001) were similarly greater on sativex vs. placebo.

An open-label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks.
Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers
The nonpsychoactive cannabinoid, cannabidiol (CBD), has great potential for the treatment of chronic and 'breakthrough' pain that may occur in certain conditions like cancer.

'breakthrough' pain can be best alleviated with intranasal (IN) delivery.

The nasal absorption of CBD from all formulations was rapid (Tmax≤ 10 minutes).

CBD was detected in the first sample taken at 0.5 minutes after IN administration of all the treatments indicating rapid absorption through the nasal epithelium.

CBD was absorbed intranasally within 10 minutes with a bioavailability of 34-46%