Nose-to-brain Delivery of Natural Compounds for the Treatment of Central Nervous System Disorders.

“Several natural compounds have demonstrated potential for the treatment of central nervous system disorders such as ischemic cerebrovascular disease, glioblastoma, neuropathic pain, neurodegenerative diseases, multiple sclerosis and migraine.

This is due to their well-known antioxidant, anti-inflammatory, neuroprotective, anti-tumor, anti-ischemic and analgesic properties. Nevertheless, many of these molecules have poor aqueous solubility, low bioavailability and extensive gastrointestinal and/or hepatic first-pass metabolism, leading to a quick elimination as well as low serum and tissue concentrations.

Thus, the intranasal route emerged as a viable alternative to oral or parenteral administration, by enabling a direct transport into the brain through the olfactory and trigeminal nerves. With this approach, the blood-brain barrier is circumvented and peripheral exposure is reduced, thereby minimizing possible adverse effects.

OBJECTIVE:

Herein, brain-targeting strategies for the nose-to-brain delivery of natural compounds, including flavonoids, cannabinoids, essential oils and terpenes, will be reviewed and discussed. Brain and plasma pharmacokinetics of these molecules will be analyzed and related to their physicochemical characteristics and formulation properties.

CONCLUSION:

Natural compounds constitute relevant alternatives for the treatment of brain diseases but often require loading into nanocarrier systems to reach the central nervous system in sufficient concentrations. Future challenges lie in a deeper characterization of their therapeutic mechanisms and in the development of effective, safe and brain-targeted delivery systems for their intranasal administration.”

https://www.ncbi.nlm.nih.gov/pubmed/31939728

http://www.eurekaselect.com/178321/article

Is Cannabidiol a Promising Substance for New Drug Development? A Review of its Potential Therapeutic Applications.

Critical Reviews™ in Eukaryotic Gene Expression

“The pharmacological importance of cannabidiol (CBD) has been in study for several years.

CBD is the major nonpsychoactive constituent of plant Cannabis sativa and its administration is associated with reduced side effects.

Currently, CBD is undergoing a lot of research which suggests that it has no addictive effects, good safety profile and has exhibited powerful therapeutic potential in several vital areas.

It has wide spectrum of action because it acts through endocannabinoid receptors; CB1 and CB2 and it also acts on other receptors, such as GPR18, GPR55, GPR 119, 5HT1A, and TRPV2.

This indicates its therapeutic value for numerous medical conditions because of its neuroprotective and immunomodulatory properties.

Potential therapeutic applications of CBD include, analgesic, anti-inflammatory, anxiolytic, anti-arthritic, anti-depressant, anti-Alzheimer disease, anti-ischemic, neuroprotective, and anti-fibrotic.

More promising areas appear to include diabetes and cancer where CBD exhibits lesser side effects and more therapeutic benefits as compared to recent available medical therapies.

Hence, CBD is a promising substance for the development of new drug. However further research and clinical studies are required to explore its complete potential.”

Protective effects of cannabidiol on lesion-induced intervertebral disc degeneration.

“Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content…

Cannabidiol (CBD) is the major nonpsychotropic phytocannabinoid of Cannabis sativa (up to 40% of Cannabis extracts). Contrary to most cannabinoids, CBD does not produce psychotomimetic or cognitive effects. Interesting, in the last years it has been suggest that CBD produces a plethora of others pharmacological effects, including antioxidant, neuroprotective, anti-proliferative, anti-anxiety, hypnotic and antiepileptic, anti-nausea, anti-ischemic, anti-hyperalgesic, and anti-inflammatory…

The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI) and histological analyses…

 Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration.

 In summary our study revealed anti-degenerative effects of intradiscal microinjection of CBD 120 nmol. CBD represents one of the most promising candidates present in the Cannabis sativa plant for clinical use due to its remarkable lack of cognitive or psychotomimetic actions.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269422/

http://www.thctotalhealthcare.com/category/spinal-cord-injury/

Activation of Cannabinoid CB2 Receptor-Mediated AMPK/CREB Pathway Reduces Cerebral Ischemic Injury.

“The type 2 cannabinoid receptor (CB2R) was recently shown to mediate neuroprotection in ischemic injury. However, the role of CB2Rs in the central nervous system, especially neuronal and glial CB2Rs in the cortex, remains unclear. We, therefore, investigated anti-ischemic mechanisms of cortical CB2R activation in various ischemic models….

  Collectively, these data demonstrate that cortical CB2R activation by TC (trans-caryophyllene, a CB2R agonist,), ameliorates ischemic injury, potentially through modulation of AMPK/CREB signaling, and suggest that cortical CB2Rs might serve as a putative therapeutic target for cerebral ischemia.”

http://www.ncbi.nlm.nih.gov/pubmed/23414569

Medical Marijuana Is Safe for Children

“Numerous cases show clinical cannabis is effective on illnesses in children”

By  William Courtney, M.D. is CEO of Cannabis International.

“The courage and fortitude of parents who have chosen cannabis compounds to treat their children facing life-threatening illness have raised eyebrows. Some live in terror that their government will take their child away, since medical marijuana is only legal in some states. However, there are numerous cases demonstrating the benefits of clinical cannabis, which happen to threaten a very profitable healthcare industry that relies on conventional drugs, as well as political agendas.

The cannabinoid acids in cannabis have been found to have anti-proliferative, anti-neoplastic, anti-inflammatory, anti-epileptic, anti-ischemic, anti-diabetic, anti-psychotic, anti-nausea, anti-spasmodic, antibiotic, anti-anxiety, and anti-depressant functions. The anti-neoplastic action of cannabis—inhibiting development of malignant cells—was recognized in the 1970s and patented by the U.S. Department of Health and Human Services in 2003.

Out of 7,000 patients, my youngest, an 8-month-old, was diagnosed with a massive midbrain tumor. Pediatric oncologists recommended chemotherapy and radiation. Instead, the parents applied a cannabinoid concentrate to their son’s pacifier twice a day, which resulted in a significant reduction in the size of the tumor in 30 days. The response prevented a million-dollar chemo-radiation hospitalization. The child’s oncologist calls the infant a ‘miracle baby,’ but most medical experts would discount the case as anecdotal, unacceptable in a peer-reviewed journal. But the real peers are other parents reluctant to consent to the devastation of surgery, chemotherapy, and radiation—not those benefiting from the $2.6 trillion healthcare industry.

A 2-year-old spent a year in a pediatric oncology ward, endured 39 hours of brain surgery, received chemotherapy, a bone marrow transplant, and radiation under general anesthesia for 42 days, only to be discharged home on hospice and morphine. The child’s local pediatrician started to treat her with juiced raw cannabis leaf. Two years later, she is still alive, now free of cancer and scar tissue.

A 6-year-old patient with a severe, intractable form of childhood epilepsy, was tried on 11 anti-epileptics, including experimental European drugs. He was finally placed on a drug commonly used to prevent seizures, but continued having 300-400 seizures a day. An ointment produced from cannabis with an increased amount of cannabidiol, a compound patented by HHS, has reduced his seizures to one every 3-4 days.

Several years ago, I proposed that cannabis be recognized as an essential nutrient in the diet of individuals in their 30s and older. Children were excluded out of fear of backlash but it is now my incontrovertible opinion that the immune system of the 8-month-old would never have allowed the tumor to gain a foothold if supported with dietary cannabis, or Vitamin F.

We know Vitamin C deficiency results in scurvy and Vitamin D deficiency results in rickets. Vitamin F, the previous label for Omega-3 and -6 essential fatty acids, is an appropriate appellation for the cannabinoid acids found in cannabis. Vitamin F deficiency allows the cell proliferation found in tumors and cancer. Three studies of over 24,000 children have shown no adverse effects from use of cannabis in pregnancy.

There is no other area in medicine where the heavy hand of federal funding and political agenda compromise valid and reproducible findings to this extent. To advance disease prevention and benign therapy, we must re-examine our preconceptions.”

http://www.usnews.com/opinion/articles/2013/01/07/medical-marijuana-is-safe-for-children