Cannabinoid receptor 1 binding activity and quantitative analysis of Cannabis sativa L. smoke and vapor.

cpb

“Cannabis sativa L. (cannabis) extracts, vapor produced by the Volcano vaporizer and smoke made from burning cannabis joints were analyzed by GC-flame ionization detecter (FID), GC-MS and HPLC. Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol.

Cannabinoids plus other components such as terpenoids and pyrolytic by-products were identified and quantified in all samples. Cannabis vapor and smoke was tested for cannabinoid receptor 1 (CB1) binding activity and compared to pure Delta(9)-tetrahydrocannabinol (Delta(9)-THC).

The top five major compounds in Bedrocan extracts were Delta(9)-THC, cannabigerol (CBG), terpinolene, myrcene, and cis-ocimene in Bedrobinol Delta(9)-THC, myrcene, CBG, cannabichromene (CBC), and camphene in Bediol cannabidiol (CBD), Delta(9)-THC, myrcene, CBC, and CBG.

The major components in Bedrocan vapor (>1.0 mg/g) were Delta(9)-THC, terpinolene, myrcene, CBG, cis-ocimene and CBD in Bedrobinol Delta(9)-THC, myrcene and CBD in Bediol CBD, Delta(9)-THC, myrcene, CBC and terpinolene.

The major components in Bedrocan smoke (>1.0 mg/g) were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene.

There was no statistically significant difference between CB1 binding of pure Delta(9)-THC compared to cannabis smoke and vapor at an equivalent concentration of Delta(9)-THC.”

http://www.ncbi.nlm.nih.gov/pubmed/20118579

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Medicinal cannabis: Principal cannabinoids concentration and their stability evaluated by a high performance liquid chromatography coupled to diode array and quadrupole time of flight mass spectrometry method.

“In the last few years, there has been a boost in the use of cannabis-based extracts for medicinal purposes, although their preparation procedure has not been standardized but rather decided by the individual pharmacists.

The present work describes the development of a simple and rapid high performance liquid chromatography method with UV detection (HPLC-UV) for the qualitative and quantitative determination of the principalcannabinoids (CBD-A, CBD, CBN, THC and THC-A) that could be applied to all cannabis-based medicinal extracts (CMEs) and easily performed by a pharmacist.

In order to evaluate the identity and purity of the analytes, a high-resolution mass spectrometry (HPLC-ESI-QTOF) analysis was also carried out. Full method validation has been performed in terms of specificity, selectivity, linearity, recovery, dilution integrity and thermal stability. Moreover, the influence of the solvent (ethyl alcohol and olive oil) was evaluated on cannabinoids degradation rate.

An alternative extraction method has then been proposed in order to preserve cannabis monoterpene component in final CMEs.”

http://www.ncbi.nlm.nih.gov/pubmed/27268223

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Study: Cannabinoids Limit Neuroblastoma Cell Proliferation

Study: Cannabinoids Limit Neuroblastoma Cell Proliferation

“The administration of the cannabinoids THC and CBD limit cancer activity in neuroblastoma cells in culture and in animals, according to preclinical data published in the journal Current Oncology.

Neuroblastoma is an aggressive form of childhood cancer that often goes inadequately addressed by conventional treatment.

Investigators reported that both types of cannabinoids reduced neuroblastoma cell viability, but that CBD demonstrated superior anti-cancer ability. The study is the first to document the anti-cancer properties of CBD in this particular cancerous cell line.

They concluded, “Our findings about the activity of CBD in nbl (neuroblastoma) support and extend previous findings about the anti-tumor activities of CBD in other tumors and suggest that cannabis extracts enriched in CBD and not in THC could be suitable for the development of novel non-psychotropic therapeutic strategies in nbl.”  http://enewspf.com/2016/04/21/study-cannabinoids-limit-neuroblastoma-cell-proliferation/

“In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791143/?report=reader

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Review of Various Herbal Supplements as Complementary Treatments for Oral Cancer.

Publication Cover

“In the United States, nearly 44,000 people are diagnosed with oral or pharyngeal cancer annually. The life expectancy for those who are diagnosed have a survival rate of 57% after five years. Among them, oral cancer can be classified as benign or malignant tumors and is diagnosed at several stages in the development: premalignant conditions, premalignant lesions, and malignant cancer. The early signs of oral cancer often go unnoticed by the individual and are often discovered during routine dental examinations. Early detection and treatment may help to increase patient survival rates. The most widely used treatments for oral cancer include surgery, radiation, and chemotherapy-alone or in combination.

Preclinical and clinical evidence for the use of green tea, raspberry, asparagus, and cannabis extracts is discussed in this review. Diet changes, supplementation with antioxidants, high-dose vitamin C therapy, and cannabinoid use have been suggested to decrease cancer cell replication and increase chance of remission.

Early detection and lifestyle changes, including the use of dietary supplements in at-risk populations, are critical steps in preventing and successfully treating oral cancer. The main evidence for supplement use is currently in cancer prevention rather than treatment.

Further research, determination, and mechanism of action for bioactive compounds such as epigallocatechin, epicatechin-3-gallate, and Bowman-Birk inhibitor concentrate, through in vitro, in vivo, and clinical trials need to be completed to support the use of natural products and their effectiveness in preventative care and supporting therapeutic approaches.” http://www.ncbi.nlm.nih.gov/pubmed/26863913

http://www.tandfonline.com/doi/abs/10.3109/19390211.2015.1122693?journalCode=ijds20

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

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Anticonvulsant activity of β-caryophyllene against pentylenetetrazol-induced seizures.

“Increasing evidence suggests that plant-derived extracts and their isolated components are useful for treatment of seizures and, hence, constitute a valuable source of new antiepileptic drugs with improved efficacy and better adverse effect profile.

β-Caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species and displays a number of biological actions, including neuroprotective activity.

In the present study, we tested the hypothesis that β-caryophyllene displays anticonvulsant effects.

Altogether, the present data suggest that β-caryophyllene displays anticonvulsant activity against seizures induced by PTZ in mice.

Since no adverse effects were observed in the same dose range of the anticonvulsant effect, β-caryophyllene should be further evaluated in future development of new anticonvulsant drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/26827298

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

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Cannabinoid receptor signaling in progenitor/stem cell proliferation and differentiation.

“Cannabinoids, the active components of cannabis (Cannabis sativa) extracts, have attracted the attention of human civilizations for centuries, much earlier than the discovery and characterization of their substrate of action, the endocannabinoid system (ECS).

The latter is an ensemble of endogenous lipids, their receptors [in particular type-1 (CB1) and type-2 (CB2) cannabinoid receptors] and metabolic enzymes.

Cannabinoid signaling regulates cell proliferation, differentiation and survival, with different outcomes depending on the molecular targets and cellular context involved.

Cannabinoid receptors are expressed and functional from the very early developmental stages, when they regulate embryonic and trophoblast stem cell survival and differentiation, and thus may affect the formation of manifold adult specialized tissues derived from the three different germ layers (ectoderm, mesoderm and endoderm).

In the ectoderm-derived nervous system, both CB1 and CB2 receptors are present in neural progenitor/stem cells and control their self-renewal, proliferation and differentiation. CB1 and CB2 show opposite patterns of expression, the former increasing and the latter decreasing along neuronal differentiation.

Recently, endocannabinoid (eCB) signaling has also been shown to regulate proliferation and differentiation of mesoderm-derived hematopoietic and mesenchymal stem cells, with a key role in determining the formation of several cell types in peripheral tissues, including blood cells, adipocytes, osteoblasts/osteoclasts and epithelial cells.

Here, we will review these new findings, which unveil the involvement of eCB signaling in the regulation of progenitor/stem cell fate in the nervous system and in the periphery.

The developmental regulation of cannabinoid receptor expression and cellular/subcellular localization, together with their role in progenitor/stem cell biology, may have important implications in human health and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/24076098

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A pharmacological basis of herbal medicines for epilepsy.

“Epilepsy is the most common chronic neurological disease, affecting about 1% of the world’s population during their lifetime. Most people with epilepsy can attain a seizure-free life upon treatment with antiepileptic drugs (AEDs).

Unfortunately, seizures in up to 30% do not respond to treatment. It is estimated that 90% of people with epilepsy live in developing countries, and most of them receive no drug treatment for the disease. This treatment gap has motivated investigations into the effects of plants that have been used by traditional healers all over the world to treat seizures.

Extracts of hundreds of plants have been shown to exhibit anticonvulsant activity in phenotypic screens performed in experimental animals.

Some of those extracts appear to exhibit anticonvulsant efficacy similar to that of synthetic AEDs.

Dozens of plant-derived chemical compounds have similarly been shown to act as anticonvulsants in various in vivo and in vitro assays.

To a significant degree, anticonvulsant effects of plant extracts can be attributed to widely distributed flavonoids, (furano)coumarins, phenylpropanoids, and terpenoids.

Flavonoids and coumarins have been shown to interact with the benzodiazepine site of the GABAA receptor and various voltage-gated ion channels, which are targets of synthetic AEDs.

Modulation of the activity of ligand-gated and voltage-gated ion channels provides an explanatory basis of the anticonvulsant effects of plant secondary metabolites.

Many complex extracts and single plant-derived compounds exhibit antiinflammatory, neuroprotective, and cognition-enhancing activities that may be beneficial in the treatment of epilepsy.

Thus, botanicals provide a base for target-oriented antiepileptic drug discovery and development.

In the future, preclinical work should focus on the characterization of the effects of plant extracts and plant-derived compounds on well-defined targets rather than on phenotypic screening using in vivo animal models of acute seizures. At the same time, available data provide ample justification for clinical studies with selected standardized botanical extracts and plant-derived compounds.”

http://www.ncbi.nlm.nih.gov/pubmed/26074183

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

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Marijuana Use in Epilepsy: The Myth and the Reality.

“Marijuana has been utilized as a medicinal plant to treat a variety of conditions for nearly five millennia.

Over the past few years, there has been an unprecedented interest in using cannabis extracts to treat epilepsy, spurred on by a few refractory pediatric cases featured in the media that had an almost miraculous response to cannabidiol-enriched marijuana extracts.

This review attempts to answer the most important questions a clinician may have regarding the use of marijuana in epilepsy. First, we review the preclinical and human evidences for the anticonvulsant properties of the different cannabinoids, mainly tetrahydrocannabinol (THC) and cannabidiol (CBD).

Then, we explore the safety data from animal and human studies. Lastly, we attempt to reconcile the controversy regarding physicians’ and patients’ opinions about whether the available evidence is sufficient to recommend the use of marijuana to treat epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/26299273

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

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(1)H NMR and HPLC/DAD for Cannabis sativa L. chemotype distinction, extract profiling and specification.

“The medicinal use of different chemovars and extracts of Cannabis sativa L. requires standardization beyond ∆9-tetrahydrocannabinol (THC) with complementing methods.

We investigated the suitability of (1)H NMR key signals for distinction of four chemotypes measured in deuterated dimethylsulfoxide together with two new validated HPLC/DAD methods used for identification and extract profiling based on the main pattern of cannabinoids and other phenolics alongside the assayed content of THC, cannabidiol (CBD), cannabigerol (CBG) their acidic counterparts (THCA, CBDA, CBGA), cannabinol (CBN) and cannflavin A and B. Effects on cell viability (MTT assay, HeLa) were tested.

The dominant cannabinoid pairs allowed chemotype recognition via assignment of selective proton signals and via HPLC even in cannabinoid-low extracts from the THC, CBD and CBG type.

Substantial concentrations of cannabinoid acids in non-heated extracts suggest their consideration for total values in chemotype distinction and specifications of herbal drugs and extracts.

Cannflavin A/B are extracted and detected together with cannabinoids but always subordinated, while other phenolics can be accumulated via fractionation and detected in a wide fingerprint but may equally serve as qualitative marker only.

Cell viability reduction in HeLa was more determined by the total cannabinoid content than by the specific cannabinoid profile.

Therefore the analysis and labeling of total cannabinoids together with the content of THC and 2-4 lead cannabinoids are considered essential.

The suitability of analytical methods and the range of compound groups summarized in group and ratio markers are discussed regarding plant classification and pharmaceutical specification.”

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Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy.

“Oral cannabis extracts (OCEs) have been used in the treatment of epilepsy; however, no studies demonstrate clear efficacy. We report on a cohort of pediatric patients with epilepsy who were given OCE and followed in a single tertiary epilepsy center…

Seventy-five patients were identified of which 57% reported any improvement in seizure control and 33% reported a >50% reduction in seizures (responders).

Our retrospective study of OCE use in pediatric patients with epilepsy demonstrates that some families reported patient improvement with treatment;

We strongly support the need for controlled, blinded studies to evaluate the efficacy and safety of OCE for treatment of pediatric epilepsies using accurate seizure counts, formal neurocognitive assessments, as well as EEG as a biomarker.

This study provides Class III evidence that OCE is well tolerated by children and adolescents with epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/25845492

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

 

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