Hemp (Cannabis sativa L.).

“Hemp (Cannabis sativa L.) suspension culture cells were transformed with Agrobacterium tumefaciens strain EHA101 carrying the binary plasmid pNOV3635. The plasmid contains a phosphomannose isomerase (PMI) selectable marker gene. Cells transformed with PMI are capable of metabolizing the selective agent mannose, whereas cells not expressing the gene are incapable of using the carbon source and will stop growing. Callus masses proliferating on selection medium were screened for PMI expression using a chlorophenol red assay. Genomic DNA was extracted from putatively transformed callus lines, and the presence of the PMI gene was confirmed using PCR and Southern hybridization. Using this method, an average transformation frequency of 31.23% ± 0.14 was obtained for all transformation experiments, with a range of 15.1-55.3%.”

http://www.ncbi.nlm.nih.gov/pubmed/25416268

Id-1 is a key transcriptional regulator of glioblastoma aggressiveness and a novel therapeutic target.

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“Glioblastoma (GBM) is the most common form of primary adult brain tumors…

It is, therefore, essential to discover master regulators that control GBM invasiveness and target them therapeutically.

We demonstrate here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of GBM cell lines and primary GBM cells.

Furthermore, we show that a non-toxic compound, cannabidiol, significantly down-regulates Id-1 gene expression and associated glioma cell invasiveness…

Our results suggest that Id-1 regulates multiple tumor-promoting pathways in GBM, and that drugs targeting Id-1 represent a novel and promising strategy for improving the therapy and outcome of GBM patients.

We previously showed a strong correlation between Id-1 expression and the invasive and metastatic behavior of breast cancer cells.”

“Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells… CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells…  Moreover, reducing Id-1 expression with cannabinoids could also provide a therapeutic strategy for the treatment of additional aggressive cancers because Id-1 expression was found to be up-regulated during the progression of almost all types…”  http://mct.aacrjournals.org/content/6/11/2921.long

“In this report, we show that Id-1 is a key regulator of brain tumor cell invasiveness and neurosphere growth, and that Id-1 expression is specifically up-regulated in tissues from patients with high-grade gliomas. Importantly, we demonstrate that targeting Id-1 expression using either genetic approaches or the non-toxic cannabinoid, cannabidiol (CBD), leads to a significant reduction in the invasion of both GBM cell lines and patient-derived primary GBM cultures. CBD also significantly inhibits GBM dispersal ex vivo, and reduces tumor growth and Id-1 expression in vivo.

Consistent with the breast cancer study, we found that the non-psychoactive cannabinoid CBD significantly down-regulated Id-1 expression in serum-derived and primary GBM cells. As expected, we observed robust inhibition of glioma cell invasiveness.

In conclusion, our results establish Id-1 as a key regulator of both invasion and stemness in GBM cells and demonstrate that the non-toxic cannabinoid compound CBD down-regulates Id-1 expression and tumor aggressiveness in culture and in vivo.

The data also shed light on some of the key pathways that control GBM cell dispersal and progression. A greater understanding of these pathways may lead to more effective therapies for cancer patients including the additional refinement of cannabinoid analogs targeting Id-1.

We expect our efforts to ultimately translate to the development of future clinical trials with nontoxic compounds that target the expression of Id-1, a master regulator of GBM aggressiveness.

With its lack of systemic toxicity and psychoactivity, CBD is an ideal candidate agent in this regard and may prove useful in combination with front-line agents for the treatment of patients with aggressive and high-grade GBM tumors.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594064/

“McAllister Lab… Cannabidiol inhibits tumor (glioblastoma) progression in mouse models of brain cancer. Mice bearing human brain tumors derived from glioblastoma were treated with the naturally occurring cannabinoid, cannabidiol (CBD).”  http://www.cpmcri-currents.org/our-people/discovery-investigators/mcallister-lab

“New Study Finds Cannabis Compound Could Have Even Greater Reach in Inhibiting Aggressive Cancer than Previously Thought. Researchers at California Pacific Medical Center Research Institute (CPMCRI, a Sutter Health affiliate) have found that a compound in cannabis previously shown to decrease metastatic breast cancer now shows promise in stopping aggressive brain cancer as well. The findings are particularly important given the safety of the cannabis compound and the fact that patients with advanced brain cancer have few options for treatment.”  http://www.cpmc.org/about/press/news2012/cannabis-brain.html

http://www.thctotalhealthcare.com/category/brain-cancer/

Glioblastoma progression in mouse models of brain cancer, after treatment with CBD

A novel hemp seed meal protein hydrolysate reduces oxidative stress factors in spontaneously hypertensive rats.

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“This report shows the antioxidant effects of a hemp seed meal protein hydrolysate (HMH) in spontaneously hypertensive rats (SHR)…

The results suggest that HMH contained antioxidant peptides that reduced the rate of lipid peroxidation in SHRs with enhanced antioxidant enzyme levels and total antioxidant capacity.”

http://www.ncbi.nlm.nih.gov/pubmed/25493943

“Cannabis sativa L., also commonly called industrial hemp seed, is historically an important source of food, fibre, dietary oil and medicine; the seed contains about 30% oil and 25% protein…

Proteins from both plant and animal sources, including those of hemp seed, have been isolated and recognized as essential sources of bioactive peptides capable of exerting various in vitro and in vivo activities, such as antioxidant, antihypertensive, antimicrobial, opioid, antithrombotic, hypocholesterolemic, appetite-reducing, mineral-binding, immunomodulatory and cytomodulatory…

HMH may serve as an important ingredient to formulate antioxidant diets with potential therapeutic effects.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276990/

http://www.thctotalhealthcare.com/category/hypertension-high-blood-pressure/

The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain.

European Neuropsychopharmacology Home

“The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressedcannabinoid receptor 2 (CB₂).

…the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions.

Cannabis preparations, which have been used since thousands of years for the treatment of pain have recently come again into the focus as potential therapeutics for inflammatory and neuropathic pain conditions. Currently, cannabis extracts and synthetic preparations of the psychoactive cannabis compound Δ9-tetrahydrocannabinol (THC) have been approved in many countries for clinical pain management at doses and formulations that show on only minor central side effects…

A natural selective agonist for CB2 receptors is the plant volatile BCP, which represents a dietary phytocannabinoid. BCP is found in large amounts in the essential oils of many common spices and food plants… Several health effects have been attributed to BCP or medicinal plants containing BCP, including anti-inflammatory, local anesthetic, anti-carcinogenic, anti-fibrotic and anxiolytic-like activity.

In the present study, we investigated the analgesic effects of BCP in formalin-induced inflammation model and in a model of neuropathic pain, which involves the partial ligation of the sciatic nerve… BCP is the first natural CB2 receptor agonist, which could orally reduce inflammatory responses in different animal models of pain.

Thus, it is likely that BCP belongs to a group of common plant natural products with major potential impact on human health.

The oral intake of this dietary cannabinoid with vegetable food could be advantageous in the daily routine clinical practice over synthetic cannabinoid agonists.”

http://www.europeanneuropsychopharmacology.com/article/S0924-977X(13)00302-7/fulltext

http://www.thctotalhealthcare.com/category/neuropathic-pain/

Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain.

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“Despite the frequency of diabetes mellitus and its relationship to diabetic peripheral neuropathy (DPN) and neuropathic pain (NeP), our understanding of underlying mechanisms leading to chronic pain in diabetes remains poor.

Recent evidence has demonstated a prominent role of microglial cells in neuropathic pain states.

One potential therapeutic option gaining clinical acceptance is the cannabinoids, for which cannabinoidreceptors (CB) are expressed on neurons and microglia. We studied the accumulation and activation of spinal and thalamic microglia in streptozotocin (STZ)-diabetic CD1 mice and the impact of cannabinoid receptor agonism/antagonism during the development of a chronic NeP state.

The prevention of microglial accumulation and activation in the dorsal spinal cord was associated with limited development of a neuropathic pain state.

Cannabinoids demonstrated antinociceptive effects in this mouse model of DPN.

These results suggest that such interventions may also benefit humans with DPN, and their early introduction may also modify the development of the NeP state.”  http://www.ncbi.nlm.nih.gov/pubmed/20236533

“Tetrahydrocannabinol (THC), a component in marijuana, acts at both CB1 and CB2 receptors, but other forms of cannabinoids such as cannabinol and cannabidiol act predominantly at CB2 receptors. Such CB2 agonists may be potential anti-inflammatory therapies, antagonizing the 2-AG-induced recruitment of microglia and impacting upon development of an inflammatory state. Such properties may permit the cannabinoids to act in the prevention of microglial activation, perhaps limiting the development of neuropathic pain.

The present data confirm the efficacy of cannabinoid agonists, both for the CB1 and CB2 receptor, in modulation of acute thermal and tactile hypersensitivity as features of neuropathic pain. Furthermore, CB1 agonism from the onset of the offending stimulus (diabetes) normally leading to neuropathic pain ameliorated the development of a neuropathic pain state.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845559/

http://www.thctotalhealthcare.com/category/neuropathic-pain/

 

The role of cannabinoids in adult neurogenesis.

“Cannabinoids are a unique class of chemical compounds incorporating plant-derived cannabinoids (the active components of Cannabis sativa), the endogenous cannabinoids and synthetic cannabinoid ligands, and these compounds are becoming increasingly recognized for their roles in neural developmental processes.

Indeed, cannabinoids have clear modulatory roles in adult neurogenesis, likely through activation of both CB1 and CB2receptors.

In recent years a large body of literature has deciphered the signalling networks involved in cannabinoid-mediated regulation of neurogenesis. This timely review summarises the evidence that the cannabinoid system is intricately associated with neuronal differentiation and maturation of NPCs, and highlights intrinsic/extrinsic signalling mechanisms that are cannabinoid targets.

Overall these findings identify the central role of the cannabinoid system in adult neurogenesis in the hippocampus and the lateral ventricles, and hence provide insight into the processes underlying post-developmental neurogenesis in the mammalian brain.”

Smoke Your Troubles Away: Exploring the Effects of Death Cognitions on Cannabis Craving and Consumption.

“When reminded of their death, participants craved cannabis, even though there was no change in their conscious negative mood… Results indicate that cannabis served as a buffer and prevented death-related thoughts from entering consciousness, thus acting as a defense mechanism against death anxiety.”  http://www.ncbi.nlm.nih.gov/pubmed/25950588

http://www.thctotalhealthcare.com/category/anxiety-2/

Study: Pot May Improve Cognitive Functioning in Bipolar Disorder

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“Patients with severe psychiatric disorders actually function better in neurocognitive assessments when they have a history of marijuana use.

Patients with bipolar I disorder performed better in neurocognitive assessments when they had a history of marijuana use.”

http://www.theatlantic.com/health/archive/2012/08/study-pot-may-improve-cognitive-functioning-in-bipolar-disorder/261140/

“Cognitive and clinical outcomes associated with cannabis use in patients with bipolar I disorder”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408776/

European rating of drug harms.

“The present paper describes the results of a rating study performed by a group of European Union (EU) drug experts using the multi-criteria decision analysis model for evaluating drug harms.

Alcohol, heroin and crack emerged as the most harmful drugs (overall weighted harm score 72, 55 and 50, respectively). The remaining drugs had an overall weighted harm score of 38 or less, making them much less harmful than alcohol.

The outcome of this study shows that the previous national rankings based on the relative harms of different drugs are endorsed throughout the EU.

The results indicates that EU and national drug policy measures should focus on drugs with the highest overall harm, including alcohol and tobacco, whereas drugs such as cannabis and ecstasy should be given lower priority including a lower legal classification.”

http://www.ncbi.nlm.nih.gov/pubmed/25922421

http://www.thctotalhealthcare.com/category/addiction/

Inhaled cannabis reduces pain in diabetic peripheral neuropathy patients, study suggests

“A small study finds that inhaling cannabis could demonstrate a dose-dependent pain reduction in patients with diabetic peripheral neuropathy.

Researchers at the University of California, United States conducted a study in which 16 patients with painful diabetic peripheral neuropathy were given placebo, or single doses of cannabis.

These doses were either low (one per cent tetrahydrocannibinol, THC), medium (four per cent THC) or high (seven per cent THC).

Tests were first performed on baseline spontaneous pain, evoked pain and cognitive function. Subsequently, participants either inhaled the cannabis or placebo, with measurements of pain intensity and cognitive function assessed over a three-hour period.

The higher the content of THC participants inhaled, the less pain they felt. The high dose of THC had a significant effect when researchers evoked pain using foam brush and von Frey.

These are tools used to test neuropathic pain in patients – von Frey are a set of filaments that test the pain of a patients by pushing against the skin to assess when the sensation becomes painful.

Patients on the high dose of THC showed impaired performance on the neuropsychological tests, but researchers concluded the pain reduction of patients adds further evidence on the efficacy of cannabis in treating diabetic peripheral neuropathy.

The results of this study were published in the Journal of Pain and Palliative Care Pharmacology.

Earlier this month, the CBD compound in cannabis was reported by researchers as a potential treatment for diabetes.”

http://www.diabetes.co.uk/news/2015/apr/inhaled-cannabis-reduces-pain-in-diabetic-peripheral-neuropathy-patients,-study-suggests-95680845.html

“Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy.”  http://www.ncbi.nlm.nih.gov/pubmed/25843054

http://www.thctotalhealthcare.com/category/diabetes/